Austedo Xr Drug Information
Generic name: DEUTETRABENAZINE
Uses of Austedo Xr
- ® and AUSTEDO ® are indicated in adults for the treatment of: chorea associated with Huntington’s disease tardive dyskinesia AUSTEDO XR and AUSTEDO are vesicular monoamine transporter 2 (VMAT2) inhibitors indicated in adults for the treatment of: Chorea associated with Huntington’s disease Tardive dyskinesia
Dosage & Administration of Austedo Xr
| 12 mg once daily (12 mg per day) |
Side Effects of Austedo Xr
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. The studies described below were conducted with AUSTEDO tablets; adverse reactions with AUSTEDO XR extended-release tablets are expected to be similar to AUSTEDO tablets. Patients with Huntington’s Disease Study 1 was a randomized, 12-week, placebo-controlled study in patients with chorea associated with Huntington’s disease.
A total of 45 patients received AUSTEDO, and 45 patients received placebo. Patients ranged in age between 23 and 74 years (mean 54 years); 56% were male, and 92% were Caucasian. The most common adverse reactions occurring in greater than 8% of AUSTEDO-treated patients were somnolence, diarrhea, dry mouth, and fatigue.
Adverse reactions occurring in 4% or more of patients treated with AUSTEDO, and with a greater incidence than in patients on placebo, are summarized in Table 3. Table 3: Adverse Reactions in Patients with Huntington's Disease (Study 1) Experienced by at Least 4% of Patients on AUSTEDO and with a Greater Incidence than on Placebo Adverse Reaction AUSTEDO (N = 45) % Placebo (N = 45) % Somnolence 11 4 Diarrhea 9 0 Dry mouth 9 7 Fatigue 9 4 Urinary tract infection 7 2 Insomnia 7 4 Anxiety 4 2 Constipation 4 2 Contusion 4 2 One or more adverse reactions resulted in a reduction of the dose of study medication in 7% of patients in Study 1. The most common adverse reaction resulting in dose reduction in patients receiving AUSTEDO was dizziness (4%). Agitation led to discontinuation in 2% of patients treated with AUSTEDO in Study 1. Patients with Tardive Dyskinesia The data described below reflect 410 tardive dyskinesia patients participating in clinical trials. AUSTEDO was studied primarily in two 12-week, placebo-controlled trials (fixed dose, dose escalation) . The population was 18 to 80 years of age, and had tardive dyskinesia and had concurrent diagnoses of mood disorder (33%) or schizophrenia/schizoaffective disorder (63%). In these studies, AUSTEDO was administered in doses ranging from 12-48 mg per day. All patients continued on previous stable regimens of antipsychotics; 71% and 14% respective atypical and typical antipsychotic medications at study entry.
The most common adverse reactions occurring in greater than 3% of AUSTEDO-treated patients and greater than placebo were nasopharyngitis and insomnia. The adverse reactions occurring in >2% or more patients treated with AUSTEDO (12-48 mg per day) and greater than in placebo patients in two double-blind, placebo-controlled studies in patients with tardive dyskinesia (Study 1 and Study 2) are summarized in Table 4. Table 4: Adverse Reactions in 2 Placebo-Controlled Tardive Dyskinesia Studies (Study 1 and Study 2) of 12-week Treatment on AUSTEDO Reported in at Least 2% of Patients and Greater than Placebo Adverse Reaction AUSTEDO (N=279) (%) Placebo (N=131) (%) Nasopharyngitis 4 2 Insomnia 4 1 Depression/ Dysthymic disorder 2 1 Akathisia/Agitation/Restlessness 2 1 One or more adverse reactions resulted in a reduction of the dose of study medication in 4% of AUSTEDO-treated patients and in 2% of placebo-treated patients.
Warnings & Cautions for Austedo Xr
Depression and Suicidality in Patients with Huntington’s Disease Patients with Huntington’s disease
are at increased risk for depression, and suicidal ideation or behaviors (suicidality). AUSTEDO XR and AUSTEDO may increase the risk for suicidality in patients with Huntington’s disease. In a 12-week, double-blind, placebo-controlled trial, suicidal ideation was reported by 2% of patients treated with AUSTEDO, compared to no patients on placebo; no suicide attempts and no completed suicides were reported. Depression was reported by 4% of patients treated with AUSTEDO. When considering the use of AUSTEDO XR or AUSTEDO, the risk of suicidality should be balanced against the need for treatment of chorea.
All patients treated with AUSTEDO XR or AUSTEDO should be observed for new or worsening depression or suicidality. If depression or suicidality does not resolve, consider discontinuing treatment with AUSTEDO XR or AUSTEDO. Patients, their caregivers, and families should be informed of the risks of depression, worsening depression, and suicidality associated with AUSTEDO XR and AUSTEDO, and should be instructed to report behaviors of concern promptly to the treating physician. Patients with Huntington’s disease who express suicidal ideation should be evaluated immediately.
Clinical Worsening and Adverse Events in Patients with Huntington’s Disease Huntington’s disease
is a progressive disorder characterized by changes in mood, cognition, chorea, rigidity, and functional capacity over time. VMAT2 inhibitors, including AUSTEDO XR and AUSTEDO, may cause a worsening in mood, cognition, rigidity, and functional capacity. Prescribers should periodically re-evaluate the need for AUSTEDO XR or AUSTEDO in their patients by assessing the effect on chorea and possible adverse effects, including sedation/somnolence, depression and suicidality, parkinsonism, akathisia, restlessness, and cognitive decline.
It may be difficult to distinguish between adverse reactions and progression of the underlying disease; decreasing the dose or stopping the drug may help the clinician to distinguish between the two possibilities. In some patients, the underlying chorea itself may improve over time, decreasing the need for AUSTEDO XR or AUSTEDO.
QTc Prolongation
AUSTEDO XR and AUSTEDO may prolong the QT interval, but the degree of QT prolongation is not clinically significant when AUSTEDO XR or AUSTEDO is administered within the recommended dosage range . AUSTEDO XR and AUSTEDO should be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias. Certain circumstances may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including bradycardia; hypokalemia or hypomagnesemia; concomitant use of other drugs that prolong the QTc interval; and presence of congenital prolongation of the QT interval.
Neuroleptic Malignant Syndrome (NMS)
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with drugs that reduce dopaminergic transmission. While NMS has not been observed in patients receiving AUSTEDO XR or AUSTEDO, it has been observed in patients receiving tetrabenazine (a closely related VMAT2 inhibitor). Clinicians should be alerted to the signs and symptoms associated with NMS. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria, rhabdomyolysis, and acute renal failure. The diagnosis of NMS can be complicated; other serious medical illness (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal disorders can present with similar signs and symptoms.
Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology. The management of NMS should include immediate discontinuation of AUSTEDO XR and AUSTEDO; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for NMS. Recurrence of NMS has been reported with resumption of drug therapy.
If treatment with AUSTEDO XR or AUSTEDO is needed after recovery from NMS, patients should be monitored for signs of recurrence.
Akathisia, Agitation, and Restlessness
AUSTEDO XR and AUSTEDO may increase the risk of akathisia, agitation, and restlessness in patients with Huntington’s disease and tardive dyskinesia. In a 12-week, double-blind, placebo-controlled trial in patients with Huntington’s disease, akathisia, agitation, or restlessness was reported by 4% of patients treated with AUSTEDO, compared to 2% of patients on placebo; in patients with tardive dyskinesia, 2% of patients treated with AUSTEDO and 1% of patients on placebo experienced these events. Patients receiving AUSTEDO XR or AUSTEDO should be monitored for signs and symptoms of restlessness and agitation, as these may be indicators of developing akathisia.
If a patient develops akathisia during treatment with AUSTEDO XR or AUSTEDO, the AUSTEDO XR or AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.
Parkinsonism
AUSTEDO XR and AUSTEDO may cause parkinsonism in patients with Huntington’s disease or tardive dyskinesia. Parkinsonism has also been observed with other VMAT2 inhibitors. Because rigidity can develop as part of the underlying disease process in Huntington’s disease, it may be difficult to distinguish between potential drug-induced parkinsonism and progression of underlying Huntington’s disease.
Drug-induced parkinsonism has the potential to cause more functional disability than untreated chorea for some patients with Huntington’s disease. Postmarketing cases of parkinsonism in patients treated with AUSTEDO for tardive dyskinesia have been reported. Signs and symptoms in reported cases have included bradykinesia, gait disturbances, which led to falls in some cases, and the emergence or worsening of tremor.
In most cases, the development of parkinsonism occurred within the first two weeks after starting or increasing the dose of AUSTEDO. In cases in which follow-up clinical information was available, parkinsonism was reported to resolve following discontinuation of AUSTEDO therapy. If a patient develops parkinsonism during treatment with AUSTEDO XR or AUSTEDO, the AUSTEDO XR or AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.
Sedation and Somnolence Sedation is a common dose-limiting adverse reaction of
AUSTEDO XR and AUSTEDO. In a 12-week, double-blind, placebo-controlled trial examining patients with Huntington’s disease, 11% of AUSTEDO-treated patients reported somnolence compared with 4% of patients on placebo and 9% of AUSTEDO-treated patients reported fatigue compared with 4% of placebo-treated patients. Patients should not perform activities requiring mental alertness to maintain the safety of themselves or others, such as operating a motor vehicle or operating hazardous machinery, until they are on a maintenance dose of AUSTEDO XR or AUSTEDO and know how the drug affects them.
Hyperprolactinemia Serum prolactin levels were not evaluated in the
AUSTEDO XR and AUSTEDO development program. Tetrabenazine, a closely related VMAT2 inhibitor, elevates serum prolactin concentrations in humans. Following administration of 25 mg of tetrabenazine to healthy volunteers, peak plasma prolactin levels increased 4- to 5-fold.
Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if AUSTEDO XR or AUSTEDO is being considered for a patient with previously detected breast cancer. Although amenorrhea, galactorrhea, gynecomastia, and impotence can be caused by elevated serum prolactin concentrations, the clinical significance of elevated serum prolactin concentrations for most patients is unknown. Chronic increase in serum prolactin levels (although not evaluated in the AUSTEDO XR, AUSTEDO, or tetrabenazine development programs) has been associated with low levels of estrogen and increased risk of osteoporosis.
If there is a clinical suspicion of symptomatic hyperprolactinemia, appropriate laboratory testing should be done and consideration should be given to discontinuation of AUSTEDO XR and AUSTEDO.
Binding to Melanin-Containing Tissues
Since deutetrabenazine or its metabolites bind to melanin-containing tissues, it could accumulate in these tissues over time. This raises the possibility that AUSTEDO XR and AUSTEDO may cause toxicity in these tissues after extended use. Neither ophthalmologic nor microscopic examination of the eye has been conducted in the chronic toxicity studies in a pigmented species such as dogs.
Ophthalmologic monitoring in humans was inadequate to exclude the possibility of injury occurring after long-term exposure. The clinical relevance of deutetrabenazine’s binding to melanin-containing tissues is unknown. Although there are no specific recommendations for periodic ophthalmologic monitoring, prescribers should be aware of the possibility of long-term ophthalmologic effects.
Drug Interactions with Austedo Xr
Strong
CYP2D6 Inhibitors A reduction in AUSTEDO XR or AUSTEDO dose may be necessary when adding a strong CYP2D6 inhibitor in patients maintained on a stable dose of AUSTEDO XR or AUSTEDO. Concomitant use of strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine, bupropion) has been shown to increase the systemic exposure to the active dihydro-metabolites of deutetrabenazine by approximately 3-fold. The daily dose of AUSTEDO XR or AUSTEDO should not exceed 36 mg per day in patients taking strong CYP2D6 inhibitors.
Reserpine Reserpine binds irreversibly to
VMAT2 and the duration of its effect is several days. Prescribers should wait for chorea or dyskinesia to reemerge before administering AUSTEDO XR or AUSTEDO to help reduce the risk of overdosage and major depletion of serotonin and norepinephrine in the central nervous system. At least 20 days should elapse after stopping reserpine before starting AUSTEDO XR or AUSTEDO. AUSTEDO XR and AUSTEDO should not be used concomitantly with reserpine .
Monoamine Oxidase Inhibitors (MAOIs)
AUSTEDO XR and AUSTEDO are contraindicated in patients taking MAOIs. AUSTEDO XR and AUSTEDO should not be used in combination with an MAOI, or within 14 days of discontinuing therapy with an MAOI .
Neuroleptic Drugs
The risk of parkinsonism, NMS, and akathisia may be increased by concomitant use of AUSTEDO XR or AUSTEDO with dopamine antagonists or antipsychotics.
Alcohol or Other Sedating Drugs
Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence.
Concomitant Tetrabenazine or Valbenazine
AUSTEDO XR and AUSTEDO are contraindicated in patients currently taking tetrabenazine or valbenazine. AUSTEDO XR or AUSTEDO may be initiated the day following discontinuation of tetrabenazine.
Pregnancy Safety for Austedo Xr
Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of AUSTEDO XR or AUSTEDO in pregnant women. Administration of deutetrabenazine to rats during organogenesis produced no clear adverse effect on embryofetal development. However, administration of tetrabenazine to rats throughout pregnancy and lactation resulted in an increase in stillbirths and postnatal offspring mortality.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of deutetrabenazine (5, 10, or 30 mg/kg/day) or tetrabenazine (30 mg/kg/day) to pregnant rats during organogenesis had no clear effect on embryofetal development.
The highest dose tested was 6 times the maximum recommended human dose of 48 mg/day, on a body surface area (mg/m 2 ) basis. The effects of deutetrabenazine when administered during organogenesis to rabbits or during pregnancy and lactation to rats have not been assessed. Tetrabenazine had no effects on embryofetal development when administered to pregnant rabbits during the period of organogenesis at oral doses up to 60 mg/kg/day.
When tetrabenazine was administered to female rats (doses of 5, 15, and 30 mg/kg/day) from the beginning of organogenesis through the lactation period, an increase in stillbirths and offspring postnatal mortality was observed at 15 and 30 mg/kg/day, and delayed pup maturation was observed at all doses.
Pediatric Use of Austedo Xr
Pediatric Use Chorea associated with Huntington’s Disease and Tardive Dyskinesia The safety and effectiveness of AUSTEDO XR and AUSTEDO have not been established in pediatric patients for the treatment of chorea associated with Huntington’s disease or for the treatment of tardive dyskinesia. Tourette Syndrome The safety and effectiveness of AUSTEDO XR and AUSTEDO have not been established in pediatric patients for the treatment of Tourette syndrome. Efficacy was not demonstrated in two randomized, double-blind, placebo-controlled studies in pediatric patients aged 6 to 16 years with Tourette syndrome.
One study evaluated fixed doses of deutetrabenazine over 8 weeks (NCT03571256); the other evaluated flexible doses of deutetrabenazine over 12 weeks (NCT03452943). The studies included a total of 274 pediatric patients who received at least one dose of deutetrabenazine or placebo. The primary efficacy endpoint in both studies was the change from baseline to end-of-treatment on the Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS). The estimated treatment effect of deutetrabenazine on the YGTSS-TTS was not statistically significantly different from placebo in either study. The placebo subtracted least squares means difference in YGTSS-TTS from baseline to end-of-treatment was -0.7 (95% CI: -4.1, 2.8) in the flexible dose study and -0.8 (95% CI: -3.9, 2.3) for the primary analysis in the fixed dose study.
The following adverse reactions were reported in frequencies of at least 5% of pediatric patients treated with AUSTEDO and with a greater incidence than in pediatric patients receiving placebo (AUSTEDO vs placebo): headache (includes: migraine, migraine with aura, and headache; 13% vs 9%), somnolence (includes: sedation, hypersomnia, and somnolence; 11% vs 2%), fatigue (8% vs 3%), increased appetite (5% vs <1%), and increased weight (5% vs <1%). Juvenile Animal Toxicity Data Deutetrabenazine orally administered to juvenile rats from postnatal days 21 through 70 (at 2.5, 5, or 10 mg/kg/day) resulted in an increased incidence of tremor, hyperactivity, and adverse increases in motor activity at ≥5 mg/kg/day, and reduced body weight and food consumption at 10 mg/kg/day. There was no reproductive or early embryonic toxicity up to the highest dose. All drug-related findings were reversible after a drug-free period.
The no observed adverse effect level (NOAEL) in juvenile rats was 2.5 mg/kg/day. These drug-related findings were similar to those observed in adult rats; however, the juvenile rats were more sensitive.
Contraindications for Austedo Xr
and AUSTEDO are contraindicated in patients: With Huntington’s disease who are suicidal, or have untreated or inadequately treated depression . With hepatic impairment . Taking reserpine. At least 20 days should elapse after stopping reserpine before starting AUSTEDO XR or AUSTEDO . Taking monoamine oxidase inhibitors (MAOIs). AUSTEDO XR and AUSTEDO should not be used in combination with an MAOI, or within 14 days of discontinuing therapy with an MAOI . Taking tetrabenazine or valbenazine . Suicidal, or untreated/inadequately treated depression in patients with Huntington’s disease Hepatic impairment Taking reserpine, MAOIs, tetrabenazine, or valbenazine
Overdosage Information for Austedo Xr
Overdoses ranging from 100 mg to 1 g have been reported in the literature with tetrabenazine, a closely related VMAT2 inhibitor. The following adverse reactions occurred with overdosing: acute dystonia, oculogyric crisis, nausea and vomiting, sweating, sedation, hypotension, confusion, diarrhea, hallucinations, rubor, and tremor. Treatment should consist of those general measures employed in the management of overdosage with any central nervous system-active drug.
General supportive and symptomatic measures are recommended. Cardiac rhythm and vital signs should be monitored. In managing overdosage, the possibility of multiple drug involvement should always be considered.
The physician should consider contacting a poison control center on the treatment of any overdose. Telephone numbers for certified poison control centers are listed on the American Association of Poison Control Centers website www.aapcc.org.
Clinical Studies of Austedo Xr
Chorea Associated with Huntington’s Disease
The efficacy of AUSTEDO as a treatment for chorea associated with Huntington's disease was established primarily in Study 1, a randomized, double-blind, placebo-controlled, multi-center trial conducted in 90 ambulatory patients with manifest chorea associated with Huntington’s disease. The diagnosis of Huntington’s disease was based on family history, neurological exam, and genetic testing. Treatment duration was 12 weeks, including an 8-week dose titration period and a 4-week maintenance period, followed by a 1-week washout.
Patients were not blinded to discontinuation. AUSTEDO was started at 6 mg per day and titrated upward, at weekly intervals, in 6 mg increments until satisfactory treatment of chorea was achieved, intolerable side effects occurred, or until a maximal dose of 48 mg per day was reached. The primary efficacy endpoint was the Total Maximal Chorea Score, an item of the Unified Huntington's Disease Rating Scale (UHDRS). On this scale, chorea is rated from 0 to 4 (with 0 representing no chorea) for 7 different parts of the body.
The total score ranges from 0 to 28. Of the 90 patients enrolled, 87 patients completed the study. The mean age was 54 (range 23 to 74). Patients were 56% male and 92% Caucasian. The mean dose after titration was 40 mg per day.
Table 5 and Figure 1 summarize the effects of AUSTEDO on chorea based on the Total Maximal Chorea Score. Total Maximal Chorea Scores for patients receiving AUSTEDO improved by approximately 4.4 units from baseline to the maintenance period (average of Week 9 and Week 12), compared to approximately 1.9 units in the placebo group. The treatment effect of -2.5 units was statistically significant (p<0.0001). The Maintenance Endpoint is the mean of the Total Maximal Chorea Scores for the Week 9 and Week 12 visits.
At the Week 13 follow-up visit (1 week after discontinuation of the study medication), the Total Maximal Chorea Scores of patients who had received AUSTEDO returned to baseline (Figure 1). Table 5: Change from Baseline to Maintenance Therapy in Total Maximal Chorea (TMC) * Score in Patients with Huntington’s Disease Treated with AUSTEDO in Study 1 Motor Endpoint AUSTEDO N = 45 Placebo N = 45 p value Change in Total Chorea Score * from Baseline to Maintenance Therapy † -4.4 -1.9 <0.0001 * TMC is a subscale of the Unified Huntington's Disease Rating Scale (UHDRS) † Primary efficacy endpoint Figure 1: Total Maximal Chorea Score Over Time in Study 1 Figure 2: Distribution of the Change in Total Maximal Chorea Scores in Study 1 Figure 2 shows the distribution of values for the change in Total Maximal Chorea Score in Study 1. Negative values indicate a reduction in chorea and positive numbers indicate an increase in chorea. A patient-rated global impression of change assessed how patients rated their overall Huntington’s disease symptoms. Fifty-one percent of patients treated with AUSTEDO rated their symptoms as “Much Improved” or “Very Much Improved” at the end of treatment, compared to 20% of placebo-treated patients.
In a physician-rated clinical global impression of change, physicians rated 42% percent of patients treated with AUSTEDO as “Much Improved” or “Very Much Improved” at the end of treatment compared to 13% of placebo-treated patients. figure-01.jpg figure-02.jpg
Tardive Dyskinesia
The efficacy of AUSTEDO in the treatment for tardive dyskinesia was established in two 12‑week, randomized, double-blind, placebo-controlled, multi-center trials conducted in 335 adult ambulatory patients with tardive dyskinesia caused by use of dopamine receptor antagonists. Patients had a history of using a dopamine receptor antagonist (antipsychotics, metoclopramide) for at least 3 months (or 1 month in patients 60 years of age and older). Concurrent diagnoses included schizophrenia/schizoaffective disorder (62%) and mood disorder (33%). With respect to concurrent antipsychotic use, 64% of patients were receiving atypical antipsychotics, 12% were receiving typical or combination antipsychotics, and 24% were not receiving antipsychotics. The Abnormal Involuntary Movement Scale (AIMS) was the primary efficacy measure for the assessment of tardive dyskinesia severity.
The AIMS is a 12-item scale; items 1 to 7 assess the severity of involuntary movements across body regions and these items were used in this study. Each of the 7 items was scored on a 0 to 4 scale, rated as: 0=not present; 1=minimal, may be extreme normal (abnormal movements occur infrequently and/or are difficult to detect); 2=mild (abnormal movements occur infrequently and are easy to detect); 3=moderate (abnormal movements occur frequently and are easy to detect) or 4 =severe (abnormal movements occur almost continuously and/or of extreme intensity). The AIMS total score (sum of items 1 to 7) could thus range from 0 to 28, with a decrease in score indicating improvement. In Study 1, a 12-week, placebo-controlled, fixed-dose trial, adults with tardive dyskinesia were randomized 1:1:1:1 to 12 mg AUSTEDO, 24 mg AUSTEDO, 36 mg AUSTEDO, or placebo.
Treatment duration included a 4-week dose escalation period and an 8-week maintenance period followed by a 1-week washout. The dose of AUSTEDO was started at 12 mg per day and increased at weekly intervals in 6 mg/day increments to a dose target of 12 mg, 24 mg or 36 mg per day. The population (n= 222) was 21 to 81 years old (mean 57 years), 48% male, and 79% Caucasian.
In Study 1, the AIMS total score for patients receiving AUSTEDO demonstrated statistically significant improvement, from baseline to Week 12, of 3.3 and 3.2 units for the 36 mg and 24 mg arms, respectively, compared with 1.4 units in placebo (Study 1 in Table 6). The improvements on the AIMS total score over the course of the study are displayed in Figure 3. Data did not suggest substantial differences in efficacy across various demographic groups. The treatment response rate distribution, based on magnitude of AIMS total score from baseline to week 12 is displayed in Figure 4. The mean changes in the AIMS total score by visit are shown in Figure 3. In Study 2, a 12-week, placebo-controlled, flexible-dose trial, adults with tardive dyskinesia (n=113) received daily doses of placebo or AUSTEDO, starting at 12 mg per day with increases allowed in 6-mg increments at 1-week intervals until satisfactory control of dyskinesia was achieved, until intolerable side effects occurred, or until a maximal dose of 48 mg per day was reached. Treatment duration included a 6-week dose titration period and a 6-week maintenance period followed by a 1-week washout.
The population was 25 to 75 years old (mean 55 years), 48% male, and 70% Caucasian. Patients were titrated to an optimal dose over 6 weeks. The average dose of AUSTEDO after treatment was 38.3 mg per day.
There was no evidence suggesting substantial differences in efficacy across various demographic groups. In Study 2, AIMS total score for patients receiving AUSTEDO demonstrated statistically significant improvement by 3.0 units from baseline to endpoint (Week 12), compared with 1.6 units in the placebo group with a treatment effect of -1.4 units. Table 6 summarizes the effects of AUSTEDO on tardive dyskinesia based on the AIMS. Table 6: Improvement in AIMS Total Score in Patients Treated with AUSTEDO in Study 1 and Study 2 Study Treatment Group Primary Efficacy Measure: AIMS Total Score Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Treatment Effect (95% CI) Study 1 AUSTEDO 36 mg* (n= 55) 10.1 -3.3 -1.9 (-3.09, -0.79) AUSTEDO 24 mg (n= 49) 9.4 -3.2 -1.8 (-3.00, -0.63) AUSTEDO 12 mg (n= 60) 9.6 -2.1 -0.7 (-1.84, 0.42) Placebo (n= 58) 9.5 -
Study 2
AUSTEDO (12-48 mg/day)* (n= 56) 9.7 -3.0 -1.4 (-2.6, -0.2) Placebo (n= 57) 9.6 -1.6 *Dose that was statistically significantly different from placebo after adjusting for multiplicity. LS Mean = Least-squares mean; SD = Standard deviation; SE = Standard error; CI = 2-sided 95% confidence interval Figure 3: Least Square Means of Change in AIMS Total Score from Baseline for AUSTEDO Compared to Placebo (Study 1) SE = Standard error Figure 4: Percent of Patients with Specified Magnitude of AIMS Total Score Improvement at the End of Week 12 (Study 1) figure-03.jpg figure-04.jpg
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.
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