Xeomin Drug Information
Generic name: INCOBOTULINUMTOXINA
Acetylcholine Release Inhibitor [EPC] Neuromuscular Blocker [EPC]
Uses of Xeomin
Chronic Sialorrhea
XEOMIN is indicated for the treatment of chronic sialorrhea in patients 2 years of age and older.
Upper Limb Spasticity Upper Limb Spasticity in Adult Patients
XEOMIN is indicated for the treatment of upper limb spasticity in adult patients. Upper Limb Spasticity in Pediatric Patients, Excluding Spasticity Caused by Cerebral Palsy XEOMIN is indicated for the treatment of upper limb spasticity in pediatric patients 2 to 17 years of age, excluding spasticity caused by cerebral palsy.
Cervical Dystonia
XEOMIN is indicated for the treatment of cervical dystonia in adult patients.
Blepharospasm
XEOMIN is indicated for the treatment of blepharospasm in adult patients.
Upper Facial Lines (Glabellar Lines, Horizontal Forehead Lines, and Lateral Canthal Lines)
XEOMIN is indicated in adult patients for the temporary improvement in the appearance of upper facial lines: moderate to severe glabellar lines (GL) associated with corrugator and/or procerus muscle activity moderate to severe horizontal forehead lines (HFL) associated with frontalis muscle activity moderate to severe lateral canthal lines (LCL) associated with orbicularis oculi muscle activity.
Dosage & Administration of Xeomin
| Parotid gland(s) | 30 Units |
|---|---|
| Submandibular gland(s) | 20 Units |
| 50 Units |
Side Effects of Xeomin
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Chronic Sialorrhea Chronic Sialorrhea in Adult Patients Table 6 lists the adverse reactions that occurred in ≥3% of XEOMIN-treated patients in the double-blind, placebo-controlled phase of the study in adult patients with chronic sialorrhea . The most common adverse reactions (≥4%) were tooth extraction, dry mouth, diarrhea, and hypertension. In the controlled portion of this study, 74 patients received 100 Units of XEOMIN, and 36 patients received placebo.
XEOMIN-treated patients were 21-80 years old (mean 65 years), and were predominantly male (71%) and White (99.5%). Table 6: Adverse Reactions (≥3%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Adult Chronic Sialorrhea Study Adverse Reaction XEOMIN 100 Units (N = 74) % Placebo (N = 36) % Tooth extraction 5 0 Dry mouth 4 0 Diarrhea 4 3 Hypertension 4 3 Fall 3 0 Bronchitis 3 0 Dysphonia 3 0 Back pain 3 0 Dry eye 3 0 Chronic Sialorrhea in Pediatric Patients Table 7 lists the adverse reactions that occurred in ≥1% of XEOMIN-treated patients 6-17 years of age in the double-blind, placebo-controlled portion of the study in pediatric patients with chronic sialorrhea . Of the patients 6-17 years of age, 148 patients received a dose of XEOMIN according to body weight, and 72 patients received placebo. Thirty-five patients 2-5 years of age received an open-label dose of XEOMIN according to body weight. XEOMIN-treated patients were 2-17 years of age (mean 10 years), predominately male (63%) and White (100%). Table 7: Adverse Reactions (≥1%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Pediatric Chronic Sialorrhea Study Adverse Reaction XEOMIN (6-17 years) (N = 148) % Placebo (6-17 years) (N = 72) % Bronchitis 1 0 Headache 1 0 Nausea/Vomiting 1 0 The most frequently reported adverse reaction in patients ages 2-5 years after XEOMIN injections was nasopharyngitis (6%). In the open-label extension period, 222 patients 2-17 years of age received up to three additional treatments with XEOMIN every 16±2 weeks.
The safety profile of XEOMIN during the open-label extension period was similar to that observed in the double-blind phase of the placebo-controlled pediatric chronic sialorrhea study. Upper Limb Spasticity Upper Limb Spasticity in Adult Patients Table 8 lists the adverse reactions that occurred in ≥2% of XEOMIN-treated patients in two placebo-controlled studies in adult patients with upper limb spasticity. Study 1 and Study 2 were both double-blind, placebo-controlled studies, with an open-label extension . In the controlled portion of these studies, 283 patients received ≥120 Units to 400 Units, of which 217 patients received at least 400 Units of XEOMIN, and 182 patients received placebo.
XEOMIN-treated patients were 20-79 years of age (mean 56 years), and were predominantly male (58%), and White (84%). Table 8: Adverse Reactions (≥2%) and Greater for XEOMIN than Placebo: Double-Blind Phase of Placebo-Controlled Adult Upper Limb Spasticity Study 1 and Study 2 Adverse Reaction XEOMIN 400 Units (N = 217) % Placebo (N = 182) % Seizure 3 0 Nasopharyngitis 2 0 Dry mouth 2 1 Upper respiratory tract infection 2 1 Upper Limb Spasticity in Pediatric Patients Table 9 lists the adverse reactions that occurred in ≥2% of XEOMIN-treated patients in Study 1 in pediatric patients 2 years of age and older with upper limb spasticity. In the controlled portion of Study 1, 350 patients were randomized to one of three doses of XEOMIN: 87 received 2 Units/kg per affected upper limb, 87 received 6 Units/kg per affected upper limb, and 176 received 8 Units/kg per affected upper limb . XEOMIN-treated patients were 2 to 17 years of age (mean 7 years), 63% were male, and 90% were White. No relationship between increased dose and increased occurrence of adverse reactions was observed.
The most common adverse reactions (≥3% of XEOMIN-treated patients) at the recommended dose of XEOMIN (8 Units/kg) were nasopharyngitis and bronchitis. Table 9: Adverse Reactions (≥2%) in Patients Treated with XEOMIN 2 Units/kg or 8 Units/kg: Double-Blind Phase of Study 1 in Pediatric Upper Limb Spasticity Adverse Reactions XEOMIN 2 Units/kg N=87 % XEOMIN 8 Units/kg N=176 % Infections and infestations Nasopharyngitis 6 3 Bronchitis 2 3 Pharyngotonsillitis Includes pharyngotonsillitis, pharyngitis and tonsillitis 2 2 Upper respiratory tract infection 2 2 Respiratory tract infection viral 1 2 Injury, poisoning and procedural complications Fall 0 2 Musculoskeletal and connective tissue disorders Pain in extremity 0 2 Cervical Dystonia The data described below reflect exposure to a single intramuscular dose of XEOMIN in a placebo-controlled, Phase 3 trial in patients with cervical dystonia. In this study, 159 patients received XEOMIN (78 were randomized to receive a total dose of 120 Units, and 81 were randomized to receive a total dose of 240 Units). XEOMIN-treated patients were 18 to 79 years old (mean 53 years), and were predominantly female (66%) and Caucasian (91%). At study baseline, approximately 25% had mild, 50% had moderate, and 25% had severe cervical dystonia.
Approximately 61% of XEOMIN-treated patients had previously received another botulinum toxin type A product. Table 10 lists adverse reactions that occurred in ≥5% of XEOMIN-treated patients (in any treatment group) and greater than placebo. Table 10: Adverse Reactions (≥5%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Cervical Dystonia Study Adverse Reaction XEOMIN 120 Units (N=77) % XEOMIN 240 Units (N=82) % Placebo (N=74) % Musculoskeletal and connective tissue disorders 23 32 11 Neck pain 7 15 4 Muscular weakness 7 11 1 Musculoskeletal pain 7 4 1 Gastrointestinal disorders 18 24 4 Dysphagia 13 18 3 Nervous system disorders 16 17 7 General disorders and administration site conditions 16 11 11 Injection site pain 9 4 7 Infections and infestations 14 13 11 Respiratory, thoracic and mediastinal disorders 13 10 3 Blepharospasm Study 1 was a randomized, double-blind, placebo-controlled study that only included treatment-naïve patients . In the controlled portion, 22 patients received XEOMIN 25 Units, 19 patients received 50 Units, and 20 patients received placebo.
XEOMIN-treated patients were 23 to 78 years of age (mean 55 years). Fifty-nine percent of the patients were women, 77% were Asian, and 23% White. No patients withdrew prematurely because of an adverse event. Table 11 lists the adverse reactions that occurred in ≥6% of XEOMIN-treated patients and greater than placebo.
Table 11: Adverse Reactions (≥6%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Blepharospasm Study 1 Adverse Reaction XEOMIN 50 U (N=19) % Placebo (N=20) % Eye disorders 21 10 Eyelid ptosis 16 0 Study 2 was a double-blind, placebo-controlled, flexible dose study with an open-label extension (OLEX) period. The study only included patients previously treated with onabotulinumtoxinA (Botox) . In the controlled portion, 74 patients received XEOMIN at a mean dose of approximately 33 Units per eye (minimum 10 Units, maximum 50 Units). XEOMIN-treated patients were 22 to 79 years of age (mean 62 years), predominantly female (65%) and Caucasian (60%). Table 12 lists the adverse reactions that occurred in ≥5% of XEOMIN-treated patients and greater than placebo. Table 12: Adverse Reactions (≥5%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Blepharospasm Study 2 Adverse Reaction XEOMIN (N=74) % Placebo (N=34) % Eye disorders 38 21 Eyelid ptosis 19 9 Dry eye 16 12 Visual impairment including vision blurred 12 6 Gastrointestinal disorders 30 15 Dry mouth 16 3 Diarrhea 8 0 Infections and infestations 20 15 Nasopharyngitis 5 3 Respiratory tract infection 5 3 Nervous system disorders 14 9 Headache 7 3 General disorders and administration site conditions 11 9 Respiratory, thoracic and mediastinal disorders 11 3 Dyspnea 5 3 Upper Facial Lines In two placebo-controlled trials in 730 adult subjects with upper facial lines (GL, HFL, and LCL), 545 subjects received up to 64 Units of XEOMIN and 185 subjects received placebo.
XEOMIN-treated subjects were 19 to 76 years old and were predominantly female (82%). Adverse reactions were reported for 62 of the 545 XEOMIN-treated subjects (11%) and for 14 of the 185 placebo-treated subjects (8%). The most frequent adverse reactions ≥1% and greater for XEOMIN than placebo are presented in Table 13. Table 13: Adverse Reactions (≥1%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Upper Facial Lines (GL, HFL, and LCL) Trials Upper Facial Lines (GL, HFL, and LCL) Adverse Reaction XEOMIN N=545 % Placebo N=185 % Injection site bruising 2 1 In the placebo-controlled trials, brow ptosis (0.7%) and injection site discomfort (0.6%) were also reported more frequently for XEOMIN than placebo-treated subjects. In the two repeated dose upper facial lines (GL, HFL, and LCL) trials with up to three treatments of XEOMIN, adverse reactions were reported for 123 of the 720 subjects (17%). Injection site hematoma was the most common adverse reaction, reported in 8% of subjects, followed by headache (3%), injection site bruising (3%) and brow ptosis (1%). The incidence of these adverse reactions tended to decrease with subsequent treatments. In both trials, all randomized subjects were followed up for 120 days before they could enter the open-label extension (OLEX) period which comprised two additional treatment cycles, with durations of 120 days each plus up to 30 days for eligibility reassessments per cycle.
During OLEX period, eligible subjects received simultaneous upper facial lines injections of XEOMIN at a total dose of 64 U in all three facial areas (20 U in GL, 20 U in HFL, and 24 U in LCL area). Glabellar Lines In three placebo-controlled trials in 803 adult subjects with glabellar lines, 535 subjects received a single dose of 20 Units of XEOMIN and 268 subjects received placebo. XEOMIN-treated subjects were 24 to 74 years old, and were predominantly female (88%). The most frequent adverse reactions ≥1% and greater for XEOMIN than Placebo are presented in Table 14. Table 14: Adverse Reactions (≥1%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Glabellar Lines Trials Adverse Reaction XEOMIN N=535 % Placebo N=263 % Nervous system disorders Headache 5 2 In the placebo-controlled trials, facial paresis (0.7%), injection site hematoma (0.6%) and eyelid edema (0.4%) were also reported more frequently for XEOMIN than placebo-treated subjects. In open-label, multiple-dose trials, adverse reactions were reported for 105 of the 800 subjects (13%). Headache was the most common adverse reaction, reported in 7% of subjects, followed by injection site hematoma (1%). Adverse reactions reported in less than 1% of subjects were: facial paresis (brow ptosis), muscle disorder (elevation of eyebrow), injection site pain, and eyelid edema.
Postmarketing Experience
The following adverse reactions have been reported during post-approval use of XEOMIN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: allergic dermatitis, dysarthria, dysphagia, eye swelling, eyelid edema, flu-like symptoms, herpes zoster, hypersensitivity, injection site pain, injection site reaction, localized allergic reactions (e.g., swelling, edema, erythema, pruritus or rash), muscle spasm, muscular weakness, myalgia, nausea, and persistent dry mouth (> 110 days).
Warnings & Cautions for Xeomin
Spread of Toxin Effect Postmarketing safety data from
XEOMIN and other approved botulinum toxins suggest that botulinum toxin effects may, in some cases, be observed beyond the site of local injection. The symptoms are consistent with the mechanism of action of botulinum toxin and may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection.
Swallowing and breathing difficulties can be life threatening and there have been reports of death related to the spread of toxin effects. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can occur in adults treated for spasticity and other conditions, and particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including lower limb spasticity in children, and in approved indications, symptoms consistent with spread of toxin effect have been reported at doses comparable to or lower than doses used to treat cervical dystonia.
Patients or caregivers should be advised to seek immediate medical care if swallowing, speech, or respiratory disorders occur.
Lack of Unit Equivalency Between Botulinum Toxin Products
The potency Units of XEOMIN are specific to the preparation and assay method utilized. Units of biological activity of XEOMIN cannot be compared to or converted into Units of any other botulinum toxin products assessed with any other specific assay method .
Hypersensitivity Reactions Serious hypersensitivity reactions have been reported with botulinum toxin products.
Hypersensitivity reactions include anaphylaxis, serum sickness, urticaria, soft tissue edema, and dyspnea. If serious and/or immediate hypersensitivity reactions occur, discontinue further injection of XEOMIN and institute appropriate medical therapy immediately. The use of XEOMIN in patients with a known hypersensitivity to any botulinum neurotoxin or to any of the excipients (human albumin, sucrose), could lead to a life-threatening allergic reaction.
Dysphagia and Breathing Difficulties Treatment with
XEOMIN and other botulinum toxin products can result in swallowing or breathing difficulties. Patients with pre-existing swallowing or breathing difficulties may be more susceptible to these complications. In most cases, this is a consequence of weakening of muscles in the area of injection that are involved in breathing or swallowing.
When distant effects occur, additional respiratory muscles may be involved . Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin. Dysphagia may persist for several months, and require use of a feeding tube to maintain adequate nutrition and hydration. Aspiration may result from severe dysphagia, and is a particular risk when treating patients in whom swallowing or respiratory function is already compromised.
Treatment of cervical dystonia with botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation. This may result in critical loss of breathing capacity in patients with respiratory disorders who may have become dependent upon these accessory muscles. There have been post-marketing reports of serious breathing difficulties, including respiratory failure, in patients with cervical dystonia treated with botulinum toxin products.
Patients with smaller neck muscle mass and patients who require bilateral injections into the sternocleidomastoid muscles have been reported to be at greater risk of dysphagia. In general, limiting the dose injected into the sternocleidomastoid muscle may decrease the occurrence of dysphagia. Patients treated with botulinum toxin may require immediate medical attention should they develop problems with swallowing, speech or respiratory disorders.
These reactions can occur within hours to weeks after injection with botulinum toxin . Patients with neuromuscular disorders with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junctional disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome) may be at increased risk for severe dysphagia and respiratory compromise from typical doses of XEOMIN.
Corneal Exposure, Corneal Ulceration, and Ectropion in Patients Treated for Blepharospasm Reduced
blinking from injection of botulinum toxin products in the orbicularis muscle can lead to corneal exposure, persistent epithelial defect, and corneal ulceration, especially in patients with VII nerve disorders. As patients with previous eye surgery may have reduced corneal sensation, carefully assess corneal sensation before treatment. Vigorous treatment of any corneal epithelial defect should be employed.
This may require protective drops, ointment, therapeutic soft contact lenses, or closure of the eye by patching or other means. Because of its anticholinergic effects, XEOMIN should be used with caution in patients at risk of developing narrow angle glaucoma. To decrease the risk for ectropion, XEOMIN should not be injected into the medial lower eyelid area.
Ecchymosis easily occurs in the soft tissues of the eyelid. Immediate gentle pressure at the injection site can limit the size.
Risk of Ptosis in Patients Treated for Glabellar Lines Do not exceed
the recommended dosage and frequency of administration of XEOMIN. In order to reduce the complication of ptosis the following steps should be taken: Avoid injection near the levator palpebrae superioris, particularly in patients with larger brow depressor complexes. Corrugator injections should be placed at least 1 cm above the bony supraorbital ridge.
Human Albumin and Transmission of Viral Diseases
This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases and variant Creutzfeldt-Jakob disease (vCJD). There is a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD), but if that risk actually exists, the risk of transmission would also be considered extremely remote. No cases of transmission of viral diseases, CJD, or vCJD have ever been identified for licensed albumin or albumin contained in other licensed products.
Pre-existing Conditions at the Injection Site Use caution when
XEOMIN is used where the targeted muscle shows excessive weakness or atrophy. Use caution when XEOMIN is used in patients who have marked facial asymmetry, with surgical alterations to the facial anatomy, pre-existing eyelid or eyebrow ptosis, when excessive weakness or atrophy is present in the target muscles, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin (e.g., the inability to substantially lessen glabellar lines even by physically spreading them apart).
Drug Interactions with Xeomin
Aminoglycosides and Other Agents Interfering with Neuromuscular Transmission Co-administration of
XEOMIN and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., tubocurarine-type muscle relaxants) should only be performed with caution as these agents may potentiate the effect of the toxin.
Anticholinergic Drugs Use of anticholinergic drugs after administration of
XEOMIN may potentiate systemic anticholinergic effects.
Other Botulinum Neurotoxin Products
The effect of administering different botulinum toxin products at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin.
Muscle Relaxants Excessive weakness may also be exaggerated by administration of a
muscle relaxant before or after administration of XEOMIN.
Pregnancy Safety for Xeomin
Units/kg, or 5.0 Units/kg on GDs 6, 18, and 28) resulted in
an increased rate of abortion at the highest dose, which was also maternally toxic. In rabbits, the no-effect level for increased abortion was
Units/kg (similar to the
MRHD for cervical dystonia on a body weight basis).
Pediatric Use of Xeomin
Pediatric Use The safety and effectiveness of XEOMIN have not been established in pediatric patients for the treatment of lower limb spasticity, cervical dystonia, and blepharospasm, or the temporary improvement in the appearance of upper facial lines: moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity moderate to severe horizontal forehead lines associated with frontalis muscle activity moderate to severe lateral canthal lines associated with orbicularis oculi muscle activity . Chronic Sialorrhea in Pediatric Patients The safety and effectiveness of XEOMIN have been established by evidence from an adequate and well-controlled study of XEOMIN in patients 6 to 17 years of age with chronic sialorrhea . Use of XEOMIN in patients 2 to 5 years of age is supported by the findings of efficacy and safety in patients 6 years and older with chronic sialorrhea, and by safety data in patients 2 to 5 years of age. Safety and effectiveness in pediatric patients below the age of 2 years have not been established. Upper Limb Spasticity in Pediatric Patients, Excluding Spasticity Caused by Cerebral Palsy Safety and effectiveness have been established in pediatric patients 2 to 17 years of age.
The safety and effectiveness of XEOMIN have been established by evidence from adequate and well-controlled studies of XEOMIN in patients 2 to 17 years of age with upper limb spasticity. A pediatric assessment for XEOMIN demonstrates that XEOMIN is safe and effective in another pediatric population. However, XEOMIN is not approved for such patient population due to marketing exclusivity for another botulinum toxin.
Safety and effectiveness in pediatric patients below the age of 2 years have not been established. Juvenile Animal Toxicity Data In a study in which juvenile rats received intramuscular injections of Xeomin (0, 5, 10, or 30 Units/kg) every other week from postnatal day 21 for 10 weeks, decreased limb use, decreased body weight gain, skeletal muscle atrophy, and decreased bone growth and density were observed at all doses. Male reproductive organ histopathology (atrophy of the germinal epithelium of the testis, associated with hypospermia) was observed at the mid and high doses, and mating behavior was impaired at the high dose.
A no-effect dose for adverse effects on development in juvenile animals was not established. The lowest dose tested (5 Units/kg) is less than the human dose of 400 Units on a body weight (kg) basis.
Contraindications for Xeomin
is contraindicated in patients with: Known hypersensitivity to any botulinum toxin product or to any of the components in the formulation . Infection at the proposed injection site(s) because it could lead to severe local or disseminated infection. Known hypersensitivity to the active substance botulinum neurotoxin type A or to any of the excipients Infection at the proposed injection sites
Overdosage Information for Xeomin
Excessive doses of XEOMIN may be expected to produce neuromuscular weakness with a variety of symptoms, particularly when treated intramuscularly. Respiratory support may be required where excessive doses cause paralysis of the respiratory muscles. In the event of overdose, the patient should be medically monitored for symptoms of excessive muscle weakness or muscle paralysis.
Symptomatic treatment may be necessary. Symptoms of overdose are not likely to be present immediately following injection. Should accidental injection or oral ingestion occur, the person should be medically supervised for several weeks for signs and symptoms of excessive muscle weakness or paralysis.
There is no significant information regarding overdose from clinical studies of XEOMIN. In the event of overdose, antitoxin raised against botulinum toxin is available from the Centers for Disease Control and Prevention (CDC) in Atlanta, GA. However, the antitoxin will not reverse any botulinum toxin-induced effects already apparent by the time of antitoxin administration. In the event of suspected or actual cases of botulinum toxin poisoning, please contact your local or state Health Department to process a request for antitoxin through the CDC. If you do not receive a response within 30 minutes, please contact the CDC directly at 770-488-7100. More information can be obtained at http://www.cdc.gov/ncidod/srp/drugs/formulary.html#1a.
Clinical Studies of Xeomin
Chronic Sialorrhea Chronic Sialorrhea in Adult Patients
The efficacy and safety of XEOMIN for the treatment of chronic sialorrhea in adult patients were evaluated in a double-blind, placebo-controlled clinical trial (NCT02091739) that enrolled a total of 184 patients with chronic sialorrhea resulting from Parkinson's disease, atypical parkinsonism, stroke, or traumatic brain injury, that was present for at least three months. Patients with a history of aspiration pneumonia, amyotrophic lateral sclerosis, salivary gland or duct malformation, and gastroesophageal reflux disease were excluded. The study consisted of a 16-week main phase, followed by an extension period of dose-blinded treatment with XEOMIN. In the main phase, a fixed total dose of XEOMIN (100 Units or 75 Units) or placebo was administered into the parotid and submandibular salivary glands in a 3:2 dose ratio.
The co-primary efficacy variables were the change in unstimulated Salivary Flow Rate (uSFR, Table 15) and the change in Global Impression of Change Scale (GICS, Table 16) at Week 4 post-injection. A total of 173 treated patients completed the main phase of the study. For both the uSFR and GICS, XEOMIN 100 Units was significantly better than placebo (see Table 15 and Table 16 ). XEOMIN 75 Units was not significantly better than placebo.
Table 15: Mean Change in uSFR (g/min) from Baseline at Week 4, 8, 12, and 16 of Main Phase XEOMIN 100 Units Placebo N=73 N=36 Week 4 p=0.004 -0.13 -0.04 Week 8 -0.13 -0.02 Week 12 -0.12 -0.03 Week 16 -0.11 -0.01 Table 16: Mean GICS at Week 4, 8, 12, and 16 of Main Phase XEOMIN 100 Units Placebo N=74 N=36 Week 4 p=0.002 1.25 0.67 Week 8 1.30 0.47 Week 12 1.21 0.56 Week 16 0.93 0.41 In the extension period, patients received up to three additional treatments with XEOMIN 100 Units or 75 Units every 16±2 weeks, for a total exposure duration of up to 64 weeks. Patients had periodic dental examinations to monitor for changes in dentition and oral mucosa. A total of 151 patients completed the extension period.
Chronic Sialorrhea in Pediatric Patients The efficacy and safety of XEOMIN for the treatment of chronic sialorrhea in pediatric patients were evaluated in a prospective, randomized, double-blind, placebo-controlled (ages 6-17 years), parallel-group, multicenter trial (NCT02270736) that enrolled and treated a total of 216 pediatric patients 6-17 years of age with chronic sialorrhea associated with cerebral palsy, other genetic or congenital disorders, or traumatic brain injury. An additional 35 patients 2-5 years of age were treated with open-label XEOMIN in that study. The study consisted of a 16-week main phase, followed by an open-label extension period of treatment with XEOMIN where patients could receive up to 3 additional treatments with XEOMIN every 16 ± 2 weeks, for a total exposure duration of up to 64 weeks (222 patients completed the extension period). In the main phase, patients 6-17 years of age were administered a total dose of XEOMIN according to body weight (up to 75 Units), or placebo, into the parotid and submandibular glands in a 3:2 dose ratio, using ultrasound guidance.
Patients 2-5 years of age all received open-label treatment with XEOMIN, according to body weight, using ultrasound guidance. Patients with a body weight <12 kg were excluded. The primary efficacy analysis was conducted in the 6-17 years of age patient group.
The co-primary endpoints were the change in unstimulated Salivary Flow Rate (uSFR, Table 17) and carer's Global Impression of Change Scale (GICS, Table 18) at Week 4 post-injection. For both the uSFR and GICS, XEOMIN was statistically significantly better than placebo (see Table 17 and Table 18 ). Table 17: Mean change in uSFR (g/min) from Baseline at Week 4, 8, 12, and 16 of Main Phase XEOMIN (6-17 years) N = 148 Placebo (6-17 years) N=72 Week 4 p=0.0012 -0.14 -0.07 Week 8 -0.16 -0.07 Week 12 -0.16 -0.06 Week 16 -0.15 -0.08 Table 18: Mean carer's GICS at Week 4, 8, 12, and 16 of Main Phase XEOMIN (6-17 years) N = 148 Placebo (6-17 years) N=72 Week 4 p=0.0320 0.91 0.63 Week 8 0.94 0.54 Week 12 0.87 0.47 Week 16 0.77 0.38 Efficacy in pediatric patients 2 to 5 years of age is extrapolated from the finding of efficacy in older pediatric patients.
Upper Limb Spasticity Upper Limb Spasticity in Adult Patients
The efficacy and safety of XEOMIN for the treatment of upper limb spasticity in adult patients were evaluated in two Phase 3, randomized, multi-center, double-blind studies. Study 1 (NCT01392300) and Study 2 (NCT00432666) were both prospective, double-blind, placebo-controlled, randomized, multi-center trials with an open-label extension period (OLEX) to investigate the efficacy and safety of XEOMIN in the treatment of post-stroke spasticity of the upper limb. For patients who had previously received botulinum toxin treatment in any body region, Study 1 and Study 2 required that ≥12 months and ≥4 months, respectively, had passed since the most recent botulinum toxin administration.
Study 1 consisted of a 12-week main phase followed by three 12-week OLEX treatment cycles for a total exposure duration of 48 weeks. The study included 317 treatment-naïve patients who were at least three months post-stroke in the main study period (210 XEOMIN and 107 placebo). During the main period, XEOMIN (fixed total dose of 400 Units) and placebo were administered intramuscularly to the defined primary target clinical pattern chosen from among the flexed elbow, flexed wrist, or clenched fist patterns and to other affected muscle groups. 296 treated patients completed the main phase and participated in the first OLEX cycle. Each OLEX cycle consisted of a single treatment session (XEOMIN 400 Units total dose, distributed among all affected muscles) followed by a 12-week observation period.
Study 2 consisted of a 12-to-20-week main phase followed by an OLEX period of 48 – 69 weeks, for up to 89 weeks of exposure to XEOMIN. The study included 148 treatment-naïve and pre-treated patients with a confirmed diagnosis of post-stroke spasticity of the upper limb who were at least six months post-stroke (73 XEOMIN and 75 placebo). During the main period, for each patient, the clinical patterns of flexed wrist and clenched fist were treated with fixed doses (90 Units and 80 Units, respectively). Additionally, if other upper limb spasticity patterns were present, the elbow, forearm and thumb muscles could be treated with fixed doses of XEOMIN per muscle. 145 patients completed the main phase and participated in the OLEX period, during which time the dosing of each involved muscle could be adapted individually. During the main and OLEX periods, the maximum total dose per treatment session and 12-week interval was 400 Units. The average XEOMIN doses injected into specific muscles and the number of injection sites per muscle in Study 1 and Study 2 are presented in Table 19. Table 19: Doses Administered to Individual Muscles (Main Period) in Adult Upper Limb Spasticity Study 1 and Study 2 Intent to Treat (ITT) Muscle Group Muscle Study 1 Units Injected Injection Site Per Muscle Study 2 Units Injected Injection Site Per Muscle XEOMIN (N=210) Mean±SD XEOMIN Median (Min; Max) XEOMIN (N=73) Mean±SD XEOMIN Median (Min; Max) All Overall 400 ± 2 Units -- 307 ± 77 Units -- Elbow flexors Overall 151 ± 50 Units 5 (1; 11) 142 ± 30 Units 5 (2; 9) Biceps 90 ± 21 Units 3 (1; 4) 80 ± 0 Units 3 (2; 4) Brachialis 52 ± 26 Units 2 (1; 4) 50 ± 0 Units 2 (1; 2) Brachioradialis 43 ± 16 Units 2 (1; 3) 60 ± 2Units 2 (1; 3) Wrist flexors Overall 112 ± 43 Units 4 (1; 6) 90 ± 0 Units 4 (4; 4) Flexor carpi radialis 58 ± 22 Units 2 (1; 3) 50 ± 0 Units 2 (2; 2) Flexor carpi ulnaris 56 ± 22 Units 2 (1; 3) 40 ± 0 Units 2 (2; 2) Finger flexors Overall 104 ± 35 Units 4 (1; 4) 80 ± 0 Units 4 (4; 4) Flexor digitorum profundus 54 ± 19 Units 2 (1; 2) 40 ± 0 Units 2 (2; 2) Flexor digitorum superficialis 54 ± 19 Units 2 (1; 2) 40 ± 0 Units 2 (2; 2) Forearm pronators Overall 52 ± 24 Units 2 (1; 3) 47 ± 16 Units 2 (1; 3) Pronator quadratus 26 ± 13 Units 1 (1; 1) 25 ± 0 Units 1 (1; 1) Pronator teres 42 ± 13 Units 1 (1; 2) 40 ± 0 Units 1.5 (1; 2) Thumb flexors/ adductors Overall 37 ± 25 Units 2 (1; 4) 25 ± 10 Units 1.5 (1; 3) Adductor pollicis 14 ± 8 Units 1 (1; 1) 10 ± 0 Units 1 (1; 1) Flexor pollicis brevis / opponens pollicis 14 ± 9 Units 1 (1; 1) 10 ± 0 Units 1 (1; 1) Flexor pollicis longus 26 ± 16 Units 1 (1; 2) 20 ± 0 Units 1 (1; 1) In Study 1, the primary efficacy variable was the change from baseline in Ashworth Scale (AS) score of the primary target clinical pattern determined by the investigator at the Week 4 visit.
The Ashworth Scale is a clinical measure of the severity of spasticity by judging resistance to passive movement. The spasticity of the elbow flexors, wrist flexors, finger flexors, and thumb muscles as well as the forearm pronators was assessed on the 0 to 4-point Ashworth scale at each visit. The co-primary efficacy variable of Study 1 was the Investigator's Global Impression of Change Scales (GICS) after 4 Weeks of treatment with XEOMIN or placebo.
The GICS is a global measure of a subject's functional improvement. Investigators were asked to evaluate the subject's global change in spasticity of the upper limb due to treatment, compared to the condition before the last injection. The response was assessed using a 7-point Likert scale that ranges from –3 (very much worse) to +3 (very much improved). XEOMIN was considered to be superior to placebo in Study 1 only if statistical significance was reached in both the AS and GICS variables.
The primary efficacy results are displayed in Table 20. Table 20: Efficacy Results by Patterns of Spasticity in Adult Upper Limb Spasticity Study 1, Week 4 Mean Change in Ashworth Scale XEOMIN (N=171) Placebo (N=88) The analysis is based on Last Observation Carried Forward in the Intent To Treat population. p<0.001 Total Primary Target Clinical Pattern (flexed wrist, flexed elbow, and clenched fist) -0.9 -
A greater percentage of
XEOMIN-treated subjects (43%) than placebo-treated subjects (23%) reported 'very much improved' and 'much improved' in their spasticity (see Figure 8 ). Figure 8: Investigator's GICS in Adult Upper Limb Spasticity Study 1 Figure 8 Upper Limb Spasticity in Pediatric Patients Study 1 (NCT02002884) was a prospective, double-blind, dose-response, randomized, multi-center trial with an open-label extension period to evaluate the efficacy and safety of XEOMIN for the treatment of upper limb spasticity in pediatric patients. Study 1 enrolled a total of 350 pediatric patients 2 to 17 years of age with upper limb spasticity in one or both upper limbs. In the double-blind main period of Study 1, patients were randomized to one of three dosages of XEOMIN: 2 Units/kg (maximum 50 Units per upper limb), 6 Units/kg (maximum 150 Units per upper limb); or 8 Units/kg (maximum 200 Units per upper limb). The maximum dose, if both upper limbs were treated, respectively was 4 Units/kg (maximum 100 Units), 12 Units/kg (maximum 300 Units), or 16 Units/kg (maximum 400 Units). For treatment of flexed elbow, injection of biceps brachii was mandatory.
The investigator could select 1 of the 2 other muscles contributing to spasticity of elbow flexion (i.e., brachialis and brachioradialis) for injection. For patients needing treatment for a flexed wrist, both the flexor carpi radialis and flexor carpi ulnaris were injected. Study 1 used a dose-response design, in which the two highest dosages of XEOMIN (8 Units/kg and 6 Units/kg) were compared to the lowest dosage (2 Units/kg), which served as control.
In the absence of a placebo control, the efficacy of the 2 Units/kg dosage of XEOMIN could not be evaluated in Study 1. The co-primary efficacy variables in Study 1 were the change from baseline on the Ashworth Scale for the primary clinical target pattern (i.e., elbow flexors or wrist flexors), and the Investigator's Global Impression of Change Scale (GICS), both at Week 4. The GICS is a global measure of a subject's functional improvement based on a 7-point Likert scale that ranges from -3 = very much worse to +3 = very much improved. As displayed in Table 21, the change from baseline in Ashworth Scale score was significantly greater for patients treated with XEOMIN 8 Units/kg than for patients treated with XEOMIN 2 Units/kg. The difference in GICS score between patients treated with XEOMIN 8 Units/kg and those treated with XEOMIN 2 Units/kg did not reach statistical significance.
However, the clinical meaningfulness of the difference in Ashworth Scale score change between patients treated with XEOMIN 8 Units/kg and those treated with XEOMIN 2 Units/kg was established by a responder analysis, in which the proportion of patients with a 1-point change or greater on the Ashworth Scale was examined. In that analysis, 86% of patients treated with XEOMIN 8 Units/kg met the responder definition, compared to 71% of patients treated with XEOMIN 2 Units/kg (nominal p value = 0.0099). There was no significant difference in change from baseline in Ashworth Scale score, GICS score, or proportion of responders between patients treated with XEOMIN 6 Units/kg and those treated with XEOMIN 2 Units/kg. Therefore, the efficacy of a 6 Units/kg dosage of XEOMIN for the treatment of upper limb spasticity in pediatric patients was not established in Study 1. Table 21: Ashworth Scale and GICS Efficacy Results in Pediatric Upper Limb Spasticity Study 1, Week 4 XEOMIN 2 Units/kg (N=87) XEOMIN 8 Units/kg (N=176) LS = Least Square Mean difference CI = Confidence Interval Ashworth Scale Mean Change from Baseline at Week 4 -0.9 -
LS Mean Difference versus
XEOMIN 2 Units/kg (95% CIs) -- -0.22 p-value versus low dose group <0.05 (-0.40, -0.04) GICS Mean at Week 4 1.6
LS Mean Difference versus
XEOMIN 2 Units/kg (95% CIs) -- 0.09 (-0.10, 0.28)
Cervical Dystonia
XEOMIN has been investigated in a randomized, double-blind, placebo-controlled, multicenter trial (NCT00407030) in a total of 233 patients with cervical dystonia. Patients had a clinical diagnosis of predominantly rotational cervical dystonia, with baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score ≥20, TWSTRS severity score ≥10, TWSTRS disability score ≥3, and TWSTRS pain score ≥1. For patients who had previously received a botulinum toxin treatment for cervical dystonia, the trial required that ≥10 weeks had passed since the most recent botulinum toxin administration. Patients with swallowing disorders or any significant neuromuscular disease that might interfere with the study were excluded from enrollment.
Patients were randomized (1:1:1) to receive a single administration of XEOMIN 240 Units (n=81), XEOMIN 120 Units (n=78), or placebo (n=74). Each patient received a single administration of 4.8 mL of reconstituted study agent (XEOMIN 240 Units, XEOMIN 120 Units, or placebo). The investigator at each site decided which muscles would receive injections of the study agent, the number of injection sites, and the volume at each site. The muscles most frequently injected were the splenius capitis/semispinalis, trapezius, sternocleidomastoid, scalene, and levator scapulae muscles. Table 22 indicates the average XEOMIN dose, and percentage of total dose, injected into specific muscles in the pivotal clinical trial.
Table 22: XEOMIN 120 Units Initial Dose (Units and % of the Total Dose) by Unilateral Muscle Injected During Double Blind Pivotal Phase 3 Study XEOMIN Dose Injected Number of Patients Injected Per Muscle Median XEOMIN Units 75 th percentile XEOMIN Units Sternocleidomastoid 63 25 35 Splenius capitis/ Semispinalis capitis 78 48 63 Trapezius 55 25 38 Levator scapulae 49 25 25 Scalenus (medius and anterior) 27 20 25 Most patients received a total of 2-10 injections into the selected muscles. Patients were assessed by telephone at one week post-injection, during clinic visits at Weeks 4 and 8, and then by telephone assessments or clinic visits every two weeks up to Week 20. The mean age of the study patients was 53 years, 66% of the patients were women, and 91% were White. At study baseline, 61% of patients had previously received a botulinum toxin as treatment for cervical dystonia.
The study was completed by 94% of study patients. Three patients discontinued the study prematurely due to adverse events: two patients in the 240 Unit group experienced musculoskeletal pain and muscle weakness, and one patient in the 120 Unit group experienced nausea and dizziness. The primary efficacy endpoint was the change in the TWSTRS total score from baseline to Week 4 post-injection, in the intent-to-treat (ITT) population, with missing values replaced by the patient's baseline value.
TWSTRS evaluates the severity of dystonia, patient-perceived disability from dystonia, and pain, with a range of possible scores from 0 to 85. The mean change in the total TWSTRS score was significantly greater for both XEOMIN groups than for the placebo group (Table 23). Table 23: Change in TWSTRS Score at Week 4 in Patients with Cervical Dystonia (Double Blind Pivotal Phase 3 Study) TWSTRS Assessment XEOMIN 240 Units (N=78) XEOMIN 120 Units (N=81) Placebo (N =74) SD = Standard Deviation, CI = Confidence Interval. Total TWSTRS at baseline 42.1 42.6
Total
TWSTRS at Week 4 31.2 32.7
Mean (SD) Change in
TWSTRS score from baseline to Week 4 -10.9 -9.9 -
Mean difference from placebo (95% CI) -9.0 (-12.0, -5.9) -7.5 (-10.4, -4.6)
p-value p-value(s) are from ANCOVA model. versus placebo <0.001 <0.001 The efficacy of XEOMIN was similar in patients who were botulinum toxin naïve and those who had received botulinum toxin prior to this study. Examination of age and gender subgroups did not identify differences in response to XEOMIN among these subgroups.
Blepharospasm Treatment-Naïve Patients
The efficacy and safety of XEOMIN for the treatment of blepharospasm in treatment-naïve patients were evaluated in Study 1 (NCT01896895), a randomized, double-blind, placebo-controlled, multi-center trial in a total of 61 patients. Patients had a clinical diagnosis of blepharospasm, with a baseline Jankovic Rating Scale (JRS) severity subscore ≥2. Patients were defined as treatment-naïve if at least 12 months had passed since their last botulinum toxin treatment for blepharospasm. During the placebo-controlled phase, a fixed total dose of 25 Units XEOMIN (n=22), 50 Units XEOMIN (n=19), or placebo (n=20) was administered intramuscularly at 6 injection sites per eye (Figure 9). Of the 61 patients randomized, 55 patients completed the placebo-controlled phase.
Patients only continued to the open-label extension (OLEX) period if they had a confirmed need for a re-injection by week 20 of the placebo-controlled phase. A total of 39 patients entered and completed the OLEX phase. The primary efficacy variable was the change from baseline in JRS Severity subscore determined at Week 6 after the injection.
The 50 Unit treatment group demonstrated statistically significant improvements compared to placebo, with a difference of -1.2 (p=0.0004). The change from baseline in the JRS Severity subscore for the 25 Unit treatment group 6 weeks after the injection was not statistically significant, with a difference of -0.5 (p=0.1452) compared to placebo (see Figure 9 ). Figure 9: Frequency Distribution of Changes from Baseline JRS Severity Subscore at Week 6 for Treatment-Naïve Patients Figure 9 Pre-Treated Patients The efficacy and safety of XEOMIN for the treatment of blepharospasm patients pre-treated with onabotulinumtoxinA (Botox) were evaluated in Study 2 (NCT00406367), a randomized, double-blind, placebo-controlled, multi-center trial in a total of 109 patients. Patients had a clinical diagnosis of benign essential blepharospasm, with baseline JRS Severity subscore ≥2, and a stable satisfactory therapeutic response to previous administrations of onabotulinumtoxinA (Botox). At least 10 weeks had to have elapsed since the most recent onabotulinumtoxinA administration. Patients with any significant neuromuscular disease that might interfere with the study were excluded from enrollment.
Patients were randomized (2:1) to receive a single administration of XEOMIN (n=75) or placebo (n=34). Each patient in the XEOMIN group received a XEOMIN treatment (dose, volume, dilution, and injection sites per muscle) that was similar to the most recent onabotulinumtoxinA injection sessions prior to study entry. The highest dose permitted in this study was 100 Units (50 Units per eye); the mean XEOMIN dose was 33 Units per eye. In Table 24 the most frequently injected sites, the median dose per injection site, and the median number (and range) of injection sites per eye are presented.
Table 24: Median Dose and Median Number of Injection Sites per Eye (Blepharospasm) Injection Area Median Units XEOMIN Median Number of Injection Sites (Min-Max) Temporal Area 13 2 (1 – 6) Eyebrow Area 5 1 (1 – 4) Upper Lid Area 10 2 (1 – 4) Lower Lid Area 8 2 (1 – 3) Orbital Rim 5 1 (1 – 3) Patients were assessed during clinic visits at Weeks 3 and 6, and then by telephone or at clinic visits every two weeks up to Week 20. The mean age of the study patients was 62 years, 65% of the patients were women, and 83% were White. The study was completed by 94% of study patients. Approximately one third of patients had other dystonic phenomena; in all but 1% this was limited to facial, cervical, perioral and mandibular muscles.
No patients discontinued the study prematurely due to adverse events. The primary efficacy endpoint was the change in the JRS Severity subscore from baseline to Week 6 post-injection, in the intent-to-treat (ITT) population, with missing values replaced by the patient's most recent value (i.e., last observation carried forward). In the ITT population, the difference between the XEOMIN group and the placebo group in the change of the JRS Severity subscore from baseline to Week 6 was -1.0 (95% CI -1.4; -0.5) points. Comparison of the XEOMIN group to the placebo group was statistically significant at p<0.001. Figure 10: Frequency Distribution of Changes from Baseline JRS Severity Subscore at Week 6 Examination of age and gender subgroups did not identify substantial differences in response to XEOMIN among these subgroups.
Figure 10
Upper Facial Lines (Glabellar Lines, Horizontal Forehead Lines, and Lateral Canthal Lines)
Two randomized, double-blind, multi-center, placebo-controlled clinical trials, Trial 1071 (NCT04594213) and Trial 1070 (NCT04622254), were conducted to evaluate XEOMIN for use in the simultaneous intramuscular treatment of upper facial lines (GL, HFL, and LCL). Each trial included an extension period with two additional open-label treatment cycles. In these two trials a total of 730 adult subjects with GL, HFL, and LCL of at least moderate severity at maximum frown as assessed by the investigator and subject were randomized and treated. In Trial 1071, a total of 362 subjects were randomized and treated.
Of the randomized subjects, 179 subjects were treated with XEOMIN in all three treatment areas (receiving 64 U in total: 20 in GL, 20 U in HFL, 24 U in LCL area), 92 subjects were treated with XEOMIN in the GL and HFL areas (receiving 20 U in the GL area and 20 U in HFL area), and 91 subjects were treated with placebo (receiving equal volume of placebo). In Trial 1070, a total of 368 subjects were randomized and treated. Of the randomized subjects, 184 subjects were treated with XEOMIN in all three treatment area (receiving 64 U in total: 20 in GL, 20 U in HFL, 24 U in LCL area), 90 subjects were treated with XEOMIN in the LCL area (receiving 24 U in LCL area, 12 U per side), and 94 subjects were treated with placebo (receiving equal volume of placebo). The mean age of the 730 treated and randomized subjects was 46.5 years. The majority of subjects were female (84%) and White (92%). Fifteen percent (15%) of subjects identified as Hispanic or Latino.
For both trials, the severity of upper facial lines (GL, HFL, and LCL) was assessed at maximum contraction using the 5-point photonumerical Merz Aesthetic Scales (MAS; 0=none, 1= mild, 2=moderate, 3=severe, 4=very severe). The MAS assessment was performed independently by both investigators and subjects. The primary timepoint was Day 30 following the first treatment. For each upper facial area (GL, HFL, or LCL), treatment success was defined as a score of 0 (none) or 1 (mild) and at least two-grade improvement from baseline to Day 30 as rated on the corresponding scale for GL, HFL, and LCL at maximum contraction as assessed by both the investigator and the subject.
The percentage of subjects with treatment success in each treatment area is presented in Table 25. Table 25. Treatment Success at Day 30 in Adults with Upper Facial Lines (GL/HFL/LCL) in Trial 1071 and Trial 1070 Trial 1071 Trial 1070 XEOMIN (20 Units GL/ 20 Units HFL/ 24 Units LCL) XEOMIN (20 Units GL/ 20 Units HFL) Placebo XEOMIN (20 Units GL/ 20 Units HFL/ 24 Units LCL) XEOMIN (24 Units LCL) N=90 Placebo N=179 N=91 N=94 N=92 N=184 GL 53% 53% 0% 49% - 0% HFL 67% 62% 0% 58% - 0% LCL 53% - 0% 33% 24% 0% Glabellar Lines Two identically designed randomized, double-blind, multi-center, placebo controlled clinical trials (Studies GL-1 and GL-2) were conducted to evaluate XEOMIN for use in the temporary improvement of moderate to severe glabellar lines. The trials enrolled 547 healthy adult patients with glabellar lines of at least moderate severity at maximum frown. Three hundred sixty six subjects were treated with 20 Units of XEOMIN and 181 subjects received placebo.
Subjects were excluded if they had marked ptosis, deep dermal scarring, or an inability to lessen glabellar lines, even by physically spreading them apart. The mean age of trial subjects was 46 years. The majority of subjects were female (86% and 93% in Studies GL-1 and GL-2, respectively), and predominantly White (89% and 65% respectively). The trial subjects received either 20 Units of XEOMIN or an equal amount of placebo.
The total dose was delivered in 5 equally divided intramuscular injections of 4 Units each to specific sites (see Figure 7 ). Subjects were followed up for 120 days. Investigators and subjects assessed efficacy at maximum frown on Day 30 of treatment using a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe). Composite treatment success was defined as a 2-grade improvement on this scale compared to baseline for both the investigator's and subject's assessments on Day 30. The percentage of subjects with treatment success was greater on the XEOMIN arm than the placebo arm at Day 30 in both trials (see Table 26 ). Table 26: Treatment Success at Day 30 (at Least 2 Grades Improvement from Baseline at Maximum Frown) in Adults with GL in Studies GL-1 and GL-2 GL-1 GL-2 XEOMIN (N=184) Placebo (N=92) XEOMIN (N=182) Placebo (N=89) Composite Treatment Success Success on both the Investigator and Subject Assessments 111 (60%) 0 (0%) 87 (48%) 0 (0%) Investigator Assessment 141 (77%) 0 (0%) 129 (71%) 0 (0%) Subject Assessment 120 (65%) 0 (0%) 101 (55%) 1 (1%)
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
Ready to save on Xeomin?
Compare prescription prices at over 70,000 pharmacies and start saving today—no enrollment required.
Compare Xeomin Prices