Nuzyra Drug Information
Generic name: OMADACYCLINE
Tetracycline-class Antibacterial [EPC]
Uses of Nuzyra
Community-Acquired Bacterial Pneumonia
NUZYRA is indicated for the treatment of adult patients with community-acquired bacterial pneumonia (CABP) caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.
Acute Bacterial Skin and Skin Structure Infections
NUZYRA is indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by the following susceptible microorganisms: Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Staphylococcus lugdunensis, Streptococcus pyogenes, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus ), Enterococcus faecalis, Enterobacter cloacae, and Klebsiella pneumoniae.
Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness
of NUZYRA and other antibacterial drugs, NUZYRA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Dosage & Administration of Nuzyra
| CABP | |
|---|---|
| ABSSSI |
Side Effects of Nuzyra
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. Overview of the Safety Evaluation of NUZYRA NUZYRA was evaluated in three Phase 3 pivotal clinical trials (Trial 1, Trial 2 and Trial 3) and one Phase 3 postmarketing clinical trial (Trial 4). These trials included one pivotal Phase 3 trial in CABP patients (Trial 1), one Phase 3 postmarketing trial in CABP patients (Trial 4), and two pivotal Phase 3 trials in ABSSSI patients (Trial 2 and Trial 3). Across all Phase 3 trials, a total of 1409 patients were treated with NUZYRA. In Trials 2 and 3, 691 patients with ABSSSI received NUZYRA, of which 368 patients were treated with only oral NUZYRA. In Trials 1 and 4, 718 patients with CABP were treated with NUZYRA. Clinical Trial Experience in Patients with Community-Acquired Bacterial Pneumonia Trial 1 was a Phase 3 CABP trial that enrolled 774 adult patients, 386 randomized to NUZYRA (382 received at least one dose of NUZYRA and 4 patients did not receive the study drug) and 388 randomized to moxifloxacin (all 388 received at least one dose of moxifloxacin). The mean age of patients treated with NUZYRA was 61 years (range 19 to 97 years) and 42% were greater than or equal to 65 years of age. Overall, patients treated with NUZYRA were predominantly male (53.7%), white (92.4%), and had a mean body mass index (BMI) of 27.3 kg/m 2. Approximately 47% of NUZYRA treated patients had CrCl <90 ml/min.
Patients were administered an IV to oral switch dosage regimen of NUZYRA. The total treatment duration was 7 to 14 days. Mean duration of IV treatment was 5.7 days and mean total duration of treatment was 9.6 days in both treatment arms. Trial 4 was a Phase 3 CABP trial that enrolled 670 adult patients, 336 randomized to NUZYRA (all 336 received at least one dose of NUZYRA) and 334 randomized to moxifloxacin (332 received at least one dose of moxifloxacin and 2 patients did not receive the study drug). The mean age of patients treated with NUZYRA was 63.3 years (range 23 to 96 years) and 47.6% were greater than or equal to 65 years of age.
Overall, patients treated with NUZYRA were predominantly male (53.0%), white (99.7%), and had a mean body mass index (BMI) of 27.0 kg/m 2. Approximately 54% of NUZYRA treated patients had CrCl <90 ml/min. Patients were administered an IV to oral switch dosage regimen of NUZYRA. The total treatment duration was 7 to 10 days with up to 14 days allowed for patients with positive blood cultures at the Screening visit. Mean duration of IV treatment was 6.6 days and mean total duration of treatment was 9.0 days in both treatment arms.
Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation In Trial 1, a total of 23/382 (6.0%) patients treated with NUZYRA and 26/388 (6.7%) patients treated with moxifloxacin experienced serious adverse reactions. There were eight deaths (2%) in 382 patients treated with NUZYRA as compared to four deaths (1%) in 388 patients treated with moxifloxacin. Discontinuation of treatment due to any adverse reactions occurred in 21/382 (5.5%) patients treated with NUZYRA and 27/388 (7.0%) patients treated with moxifloxacin.
In Trial 4, a total of 17/336 (5.1%) patients treated with NUZYRA and 15/332 (4.5%) patients treated with moxifloxacin experienced serious adverse reactions. There were six deaths (1.8%) in each treatment group (6/336 in the NUZYRA group, and 6/332 in the moxifloxacin group). Discontinuation of treatment due to any adverse reactions occurred in 9/336 (2.7%) patients treated with NUZYRA and 9/332 (2.7%) patients treated with moxifloxacin. Most Common Adverse Reactions Table 4 lists the most common adverse reactions occurring in ≥2% of CABP patients receiving NUZYRA in Trial 1 and Trial 4. Table 4: Adverse Reactions Occurring in ≥2% of CABP Patients Receiving NUZYRA in Pooled Trials 1 and Trial 4 Adverse Reaction NUZYRA (N = 718) Moxifloxacin (N = 720) Alanine aminotransferase increased 2.8
Headache 2.8 2.8 Hypertension 2.2 1.7 Aspartate aminotransferase increased 2.1 1.9 Clinical
Trials Experience in Patients with Acute Bacterial Skin and Skin Structure Infections Trial 2 was a Phase 3 ABSSSI trial that enrolled 655 adult patients, 329 randomized to NUZYRA and 326 randomized to linezolid. Trial 3 was a Phase 3 ABSSSI trial that enrolled 735 adult patients, 368 randomized to NUZYRA and 367 randomized to linezolid. In Trial 2 (IV to oral switch trial), the mean age of patients treated with NUZYRA was 47 years (range 19 to 88). Overall, patients treated with NUZYRA were predominantly male (62.8%), white (91.0%) and had a mean BMI of 28.1 kg/m 2. In Trial 3 (oral only trial), the mean age of patients was 43 years (range 18 to 86). Patients treated with NUZYRA were predominantly male (65.8%), white (88.9%), and had a mean BMI of 27.9 kg/m 2. In Trials 2 and 3, approximately 12% of NUZYRA treated patients had CrCl <90 ml/min.
Overall, the mean and median calculated lesion area was similar across both trials. Trial 2 required at least 3 days of IV treatment followed by switch to oral regimen based on physician's discretion. Mean duration of IV treatment in Trial 2 was 4 days and mean total duration of treatment was 9 days in both treatment arms.
In Trial 3, only oral therapy was administered, and mean total duration of treatment was 8 days in both treatment arms. The median days on treatment in the pooled ABSSSI trials was 9 days for both NUZYRA and linezolid. Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation In the pooled ABSSSI trials, serious adverse reactions occurred in 16/691 (2.3%) of ABSSSI patients treated with NUZYRA and 13/689 (1.9%) of patients treated with comparator.
Discontinuation of treatment due to adverse events occurred in 12 (1.7%) NUZYRA treated patients, and 10 (1.5%) comparator treated patients. There was 1 death (0.1%) reported in NUZYRA treated patients and 3 deaths (0.4%) reported in linezolid patients in ABSSSI trials. Most Common Adverse Reactions Table 5 includes the most common adverse reactions occurring in ≥2% of patients receiving NUZYRA in Trials 2 and 3. Table 5: Adverse Reactions Occurring in ≥2% of ABSSSI Patients Receiving NUZYRA in Pooled Trials 2 and 3 Adverse Reaction NUZYRA (N = 691) Linezolid (N = 689) Nausea In Trial 2, which included IV to oral dosing of NUZYRA, 40 (12%) patients experienced nausea and 17 (5%) patients experienced vomiting in NUZYRA treatment group as compared to 32 (10%) patients experienced nausea and 16 (5%) patients experienced vomiting in the comparator group.
One patient (0.3%) in the NUZYRA group discontinued treatment due to nausea and vomiting. In Trial 3, which included the oral loading dose of NUZYRA, 111 (30%) patients experienced nausea and 62 (17%) patients experienced vomiting in NUZYRA treatment group as compared to 28 (8%) patients experienced nausea and 11 (3%) patients experienced vomiting in the linezolid group. One patient (0.3%) in the NUZYRA group discontinued treatment due to nausea and vomiting 21.9
Vomiting 11.4 3.9 Infusion site reactions Infusion site extravasation, pain, erythema, swelling
inflammation, irritation, peripheral swelling and skin induration. 5.2
Diarrhea 3.2 2.9 Selected Adverse Reactions Occurring in Less Than 2% of
ABSSSI and CABP Patients Receiving NUZYRA in Trials 1, 2, 3, and 4 The following selected adverse reactions were reported in NUZYRA-treated patients at a rate of less than 2% in Trials 1, 2, 3, and 4. Cardiovascular System Disorders: tachycardia, atrial fibrillation Blood and Lymphatic System Disorders: anemia, thrombocytosis Ear and Labyrinth Disorders: vertigo Gastrointestinal Disorders: constipation, abdominal pain, dyspepsia General Disorders and Administration Site Conditions: fatigue Immune System Disorders: hypersensitivity Infections and Infestations: oral candidiasis, vulvovaginal mycotic infection Investigations: gamma glutamyl transferase increased, creatinine phosphokinase increased, bilirubin increased, lipase increased, alkaline phosphatase increased Nervous System Disorders: dysgeusia, lethargy Psychiatric Disorders: Insomnia Respiratory, Thoracic, and Mediastinal disorders: oropharyngeal pain Skin and Subcutaneous Tissue Disorders: pruritus, erythema, hyperhidrosis, urticaria
Postmarketing Experience
The following adverse reactions have been identified during post approval use of NUZYRA. 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. Skin and Subcutaneous Tissue Disorders: rash
Warnings & Cautions for Nuzyra
Tooth Discoloration and Enamel Hypoplasia
The use of NUZYRA during tooth development (last half of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the tetracycline class drugs, but it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported with tetracycline class drugs. Advise the patient of the potential risk to the fetus if NUZYRA is used during the second or third trimester of pregnancy.
Inhibition of Bone Growth
The use of NUZYRA during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every 6 hours.
This reaction was shown to be reversible when the drug was discontinued. Advise the patient of the potential risk to the fetus if NUZYRA is used during the second or third trimester of pregnancy .
Hypersensitivity Reactions Hypersensitivity reactions have been reported with
NUZYRA. Life-threatening hypersensitivity (anaphylactic) reactions have been reported with other tetracycline class antibacterial drugs. NUZYRA is structurally similar to other tetracycline class antibacterial drugs and is contraindicated in patients with known hypersensitivity to tetracycline class antibacterial drugs . Discontinue NUZYRA if an allergic reaction occurs.
Clostridioides difficile- Associated Diarrhea Clostridioides difficile- associated diarrhea (CDAD) has been reported
with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.
CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Tetracycline Class Effects
NUZYRA is structurally similar to tetracycline class of antibacterial drugs and may have similar adverse reactions. Adverse reactions including photosensitivity, fixed drug eruption, pseudotumor cerebri, and anti-anabolic action which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests, have been reported for other tetracycline class antibacterial drugs, and may occur with NUZYRA. Discontinue NUZYRA if any of these adverse reactions are suspected.
Development of Drug-Resistant Bacteria Prescribing
NUZYRA in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Drug Interactions with Nuzyra
Anticoagulant Drugs
Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage while also taking NUZYRA.
Antacids and Iron Preparations Absorption of oral tetracyclines, including
NUZYRA, is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate, and iron containing preparations.
Pregnancy Safety for Nuzyra
Pregnancy Risk Summary NUZYRA, like other tetracycline class antibacterial drugs, may cause discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimester of pregnancy. The limited available data of NUZYRA use in pregnant women is insufficient to inform drug associated risk of major birth defects and miscarriages. Animal studies indicate that administration of omadacycline during the period of organogenesis resulted in fetal loss and/or congenital malformations in pregnant rats and rabbits at 7 times and 3 times the mean AUC exposure, respectively, of the clinical intravenous dose of 100 mg and the oral dose of 300 mg.
Reductions in fetal weight occurred in rats at all administered doses (see Data ). In a fertility study, administration to rats during mating and early pregnancy resulted in embryo loss at 20 mg/kg/day; systemic exposure based on AUC was approximately equal to the clinical exposure level . Results of studies in rats with omadacycline have shown tooth discoloration. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15-20%. Data Animal Data Intravenous infusion of omadacycline to pregnant rats during organogenesis (gestation days 6-17) at doses of 5 to 80 mg/kg/day resulted in maternal lethality at 80 mg/kg/day. Increased embryo-fetal lethality and fetal malformations (whole body edema) occurred at 60 mg/kg/day (7 times the clinical AUC), dose-dependent reductions in fetal body weight occurred at all doses, and delayed skeletal ossification occurred at doses as low as 10 mg/kg/day (Systemic exposure based on AUC at a similar dose in unmated female rats in a separate study was approximately half the clinical exposure). In pregnant rabbits, intravenous infusion of 5, 10 or 20 mg/kg/day during organogenesis (gestation days 7-18) resulted in maternal lethality and body weight loss at 20 mg/kg/day. Embryo-fetal lethality, congenital malformations of the skeleton, and reduced fetal weight also occurred at 20 mg/kg/day (7 times the clinical AUC). Cardiac and lung malformations were present in dose-related incidence at 10 and 20 mg/kg/day.
The fetal no-adverse-effect-level in the rabbit embryo-fetal development study was 5 mg/kg/day, at approximately 1.2 times the clinical steady state AUC. Intravenous infusion of omadacycline to pregnant and lactating rats at doses of 7.5, 15 and 30 mg/kg/day did not adversely affect survival, growth (other than lower pup body weights and/or gains at the high dose that were only statistically significant at sporadic intervals), postnatal development, behavior, or reproductive capability of offspring at maternal doses up to 30 mg/kg/day (approximately equivalent to 3 times the IV clinical dose of 100 mg/day, based on doses normalized for total body surface area), the highest dose tested, although dosing was discontinued early in a number of animals in this group due to injection site intolerance. Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity also has been noted in animals treated early in pregnancy.
Pediatric Use of Nuzyra
Pediatric Use Safety and effectiveness of NUZYRA in pediatric patients below the age of 18 years have not been established. Due to the adverse effects of the tetracycline class of drugs, including NUZYRA on tooth development and bone growth, use of NUZYRA in pediatric patients less than 8 years of age is not recommended.
Contraindications for Nuzyra
is contraindicated in patients with known hypersensitivity to omadacycline or tetracycline class antibacterial drugs, or to any of the excipients. Known hypersensitivity to omadacycline, tetracycline class antibacterial drugs or any of the excipients in NUZYRA
Overdosage Information for Nuzyra
No specific information is available on the treatment of overdosage with NUZYRA. Following a 100 mg single dose intravenous administration of omadacycline, 8.9% of dose is recovered in the dialysate.
Clinical Studies of Nuzyra
Community-Acquired Bacterial Pneumonia
A total of 1444 adults with CABP were randomized in two multinational, double-blind, double-dummy trials (Trial 1 NCT02531438 and Trial 4 NCT04779242) comparing NUZYRA to moxifloxacin. NUZYRA was administered 100 mg intravenously every 12 hours for two doses on Day 1, followed by 100 mg intravenously daily, or 300 mg orally, daily. Moxifloxacin 400 mg was administered intravenously or orally daily.
Total treatment duration was 7-14 days. All enrolled patients were expected to require a minimum of at least 3 days of intravenous treatment. Efficacy and safety of an oral loading dose was not evaluated in CABP. In Trial 1, a total of 386 patients were randomized to NUZYRA and 388 patients were randomized to moxifloxacin.
Patient demographic and baseline characteristics were balanced between the treatment groups. Patients were predominantly male (55%) and white (92%). Approximately 60% of patients in each group belonged to PORT Risk Class III, 26% were PORT Risk Class IV and 14.5% were PORT Risk Class II. The median age was 62 years, mean BMI was 27.34 kg/m2, and approximately 47% of NUZYRA treated patients had CrCl <90 ml/min. Among NUZYRA-treated patients, common comorbid conditions included hypertension (49.5%), diabetes mellitus (16.3%), chronic lung disease (21.2%), atrial fibrillation (10.1%), and coronary artery disease (9.1%). The majority of sites were in Eastern Europe, which accounted for 82% of enrollment; 3 patients were enrolled in the US. In Trial 4, a total of 336 patients were randomized to NUZYRA and 334 patients were randomized to moxifloxacin.
Patient demographic and baseline characteristics were balanced between the treatment groups. Patients were predominantly male (51.6%) and white (99.7%). Approximately 76% of patients belonged to PORT Risk Class III, and 24% were PORT Risk Class IV. The median age was 65.0 years, mean BMI was 27.0 kg/m2, and approximately 56% of NUZYRA treated patients had CrCl <90 ml/min. Among NUZYRA-treated patients, common comorbid conditions included hypertension (49.4%), diabetes mellitus (19.6%), chronic lung disease (11.9%), atrial fibrillation (6.5%), and coronary artery disease (1.2%). All sites were in Eastern Europe.
Clinical success at the early clinical response (ECR) timepoint, 72 to 120 hours after the first dose, was defined as survival with improvement in at least two of four symptoms (cough, sputum production, chest pain, dyspnea) without deterioration in any of these four symptoms in the intent to treat population (ITT), which consisted of all randomized patients. Table 7 presents the clinical success rates at the ECR timepoint (ITT population). Table 7: Clinical Success at the ECR Timepoint in Trial 1 and Trial 4 (ITT Population) Study NUZYRA n/N (%) Moxifloxacin n/N (%) Treatment Difference (95% CI 95% confidence interval for the treatment difference ) Trial 2 301/336 293/334 +1.9 (-3.0, 6.8) * Clinical Success at the early clinical response (ECR) timepoint, 72 to 120 hours after the first dose, was defined as survival with improvement in at least two of four symptoms (cough, sputum production, chest pain, dyspnea) from baseline without deterioration in any of these symptoms, with no receipt of antibacterial treatment either as a rescue for CABP or as a treatment for other infections that may be effective for CABP, and no discontinuation of study treatment due to AE. Trial 1 313/386 321/388 -1.6 (-7.1, 3.8) Clinical response was also assessed by the investigator at the post therapy evaluation visit (PTE), 5 to 10 days after last dose of study drug and defined as survival and improvement in signs and symptoms of CABP, based on the clinician's judgment, to the extent that further antibacterial therapy is not necessary. Table 8 presents the results of clinical response at the PTE visit for both the ITT population and the Clinically Evaluable (CE) population, which consisted of all ITT patients who had a diagnosis of CABP, received a minimum number of expected doses of study drug, did not have any protocol deviations that would affect the assessment of efficacy, and had investigator assessment at the PTE visit.
Clinical response rates by most common baseline pathogen in the microbiological ITT (micro-ITT) population, defined as all randomized patients with a baseline pathogen are presented in Table 9. Table 8: Investigator's Overall Assessment of Clinical Response at PTE Investigator's overall assessment of clinical response at PTE was defined as survival and improvement in signs and symptoms of CABP, based on the clinician's judgment, to the extent that further antibacterial therapy is not necessary in the ITT and CE populations. in Trial 1 and Trial 4 (ITT and CE Population) Study Endpoint Population NUZYRA n/N (%) Moxifloxacin n/N (%) Treatment Difference (95% CI 95% confidence interval for the treatment difference. ) Trial 1 Clinical Success at PTE ITT 338/386 330/388 2.5 (-2.4, 7.4) Trial 1 Clinical Success at PTE CE 316/340 312/345 2.5 (-1.7, 6.8) Trial 4 Clinical Success at PTE ITT 289/336 293/334 -1.7 (-6.9, 3.4) Trial 4 Clinical Success at PTE CE 257/273 260/271 -1.8 (-5.7, 2.0) Table 9: Investigator's Overall Assessment of Clinical Response at PTE by Baseline Pathogen in Trial 1 and Trial 4 (micro-ITT population) Pathogen NUZYRA n/N (%) Moxifloxacin n/N (%) Streptococcus pneumoniae 58/69 47/54 Methicillin-susceptible Staphylococcus aureus ( MSSA ) 37/49 38/41 Haemophilus influenzae 52/60 34/36 Haemophilus parainfluenzae 52/59 51/56 Klebsiella pneumoniae 26/29 27/32 Legionella pneumophila 53/60 48/51 Mycoplasma pneumoniae 45/49 39/44 Chlamydophila pneumoniae 28/32 23/25
Acute Bacterial Skin and Skin Structure Infections
A total of 1390 adults with ABSSSI were randomized in two multicenter, multinational, double-blind, double-dummy trials (Trial 2 NCT02378480 and Trial 3 NCT02877927). Both trials compared 7 to 14 days of NUZYRA to linezolid. Patients with cellulitis, major abscess, or wound infection were enrolled in the trials. In Trial 2, 329 patients were randomized to NUZYRA (100 mg intravenously every 12 hours for 2 doses followed by 100 mg intravenously every 24 hours, with the option to switch to 300 mg orally every 24 hours) and 326 patients were randomized to linezolid (600 mg intravenously every 12 hours, with the option to switch to 600 mg orally every 12 hours). Patients in the trial had the following infections: cellulitis (38%), wound infection (33%), and major abscess (29%). The mean surface area of the infected lesion was 455 cm 2 in NUZYRA-treated patients and 498 cm 2 in linezolid-treated patients.
The mean age of patients was 47 years. Subjects were predominantly male (65%) and white (92%), and mean BMI was 28.1 kg/m 2. Among NUZYRA-treated patients, common comorbid conditions included drug abuse (53.9%), hepatitis C (29.1%), hypertension (20.4%), anxiety (19.5%), and depression (15.5%). Trial 2 was conducted globally including approximately 60% of patients enrolled in the United States. In Trial 3, 368 patients were randomized to NUZYRA (450 mg oral once a day on Days 1 and 2, followed by 300 mg orally once a day) and 367 were randomized to linezolid (600 mg orally every 12 hours). All patients were enrolled in the United States.
Patients in the trial had the following infections: wound infections (58%), cellulitis (24%), and major abscess (18%). The mean surface area of the infected lesion was 424 cm 2 in NUZYRA-treated patients and 399 cm 2 in linezolid-treated patients. The mean age of patients was 44 years. Subjects were predominantly male (63%) and white (91%) and mean BMI was 27.9 kg/m 2. The most common comorbid conditions included drug abuse (72.8%), tobacco use (12.0%), and chronic hepatitis C infection (31.5%). In Trials 2 and 3, approximately 12% of NUZYRA-treated patients had CrCl <90 ml/min.
In both trials, efficacy was determined by the successful early clinical response at 48 to 72 hours after the first dose in the mITT population and was defined as a 20% or greater decrease in lesion size. Table 10 summarizes the clinical response rates in the two trials. The mITT population was defined as all randomized subjects without a sole Gram-negative causative pathogen at screening.
Table 10: Clinical Success Clinical success at early clinical response (ECR) at 48 to 72 hours after the first dose, was defined as a 20% or greater decrease in lesion size without any reasons for failure (less than 20% reduction in lesion size, administration of rescue antibacterial therapy, use of another antibacterial or surgical procedure to treat for lack of efficacy, or death). at the ECR Timepoint in the mITT Population in Trial 2 and Trial 3 Study NUZYRA (%) Linezolid (%) Treatment Difference (Two-Sided 95% CI) 95% confidence interval for the treatment difference. Trial 2 84.8 85.5 -0.7 (-6.3, 4.9) Trial 3 87.3 82.2 +5.1 (-0.2, 10.5) Clinical response at the post therapy evaluation (PTE, 7 to 14 days after last dose) visit in the mITT and clinically evaluable (CE) populations was defined as survival after completion of study treatment without receiving any alternative antibacterial therapy other than NUZYRA, without unplanned major surgical intervention, and sufficient resolution of infection such that further antibacterial therapy is not needed (see Table 11 ). Clinical response rates at PTE by most common pathogen in the microbiological-mITT population, defined as all patients in the mITT population, who had at least 1 Gram- positive causative pathogen identified at baseline are provided in Table 12. The CE population consisted of all mITT patients who had a diagnosis of ABSSSI, received a minimum number of expected doses of study drug, did not have any protocol deviations that would affect the assessment of efficacy, and had investigator assessment at the PTE Visit. Table 11: Investigator's Overall Assessment of Clinical Response at PTE in mITT and CE Population in Trial 2 and Trial 3 Study Population NUZYRA n/N (%) Linezolid n/N (%) Treatment Difference (Two-Sided 95% CI) 95% confidence interval for the treatment difference.
Trial 2 mITT 272/316 260/311 +2.5 (-3.2, 8.2) CE 259/269 243/260 +2.8 (-1.0, 6.9) Trial 3 mITT 296/353 284/353 +3.4 (-2.3, 9.1) CE 272/278 272/285 +2.4 (-0.6, 5.8) Table 12: Investigator's Overall Assessment of Clinical Response at PTE by Baseline Pathogen in Trials 2 and 3 (micro-mITT population) Pathogen NUZYRA n/N (%) Linezolid n/N (%) Staphylococcus aureus 305/369 306/378 Methicillin-susceptible Staphylococcus aureus (MSSA) 164/201 181/226 Methicillin-resistant Staphylococcus aureus (MRSA) 146/173 128/157 Staphylococcus lugdunensis 10/11 2/3 Streptococcus anginosus group 84/104 59/82 Streptococcus pyogenes 28/40 25/34 Enterococcus faecalis 17/18 21/25 Enterobacter cloacae 11/14 9/11 Klebsiella pneumoniae 8/11 6/11
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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