Bioequivalence Study Comparing Naltrexone SR/Bupropion SR Trilayer Tablets From Two Manufacturers

Study Overview
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Brief Summary
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This is a Phase 1, open-label, randomized, single-dose, 2-way crossover study in healthy adult subjects to assess the bioequivalence of naltrexone SR/bupropion SR combination trilayer tablets prepared at two different manufacturing sites. The pharmacokinetics of the two drug products will be evaluated separately in the fed and fasted state.

Official Title
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A Phase 1 Bioequivalence Study of Naltrexone SR/Bupropion SR Combination Trilayer Tablets From Two Manufacturers in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Reference naltrexone 8 mg SR/bupropion 90 mg SR combination trilayer tablets (2 tablets)
* Drug: Test naltrexone 8 mg SR/bupropion 90 mg SR combination trilayer tablets (2 tablets)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 to 60 years of age, inclusive Be in good general health, without any clinically significant medical history, physical examination findings, or laboratory results at Screening or Day -1 Body mass index (BMI) of 18 to 30 kg/m2, inclusive, at Screening Exclusion Criteria: Acute (within 28 days of Day -1) or chronic illness History (within the last 20 years) of seizures, cranial trauma, bulimia, anorexia nervosa, or other conditions that may predispose the subject to seizures; or previous medical treatment with anticonvulsants of any type History of mania or current diagnosis of active psychosis Acute depressive illness, including new onset of depression or acute exacerbation of symptoms Use of any prescription medication within 14 days prior to Day -1, with the exception of hormonal contraceptive or hormonal replacement therapy (HRT) at a stable dose for at least 28 days prior to Day -1 Use of any over-the-counter medications, including dietary/nutritional and herbal supplements, within 24 hours prior to study drug intake on Day 1 Use of bupropion- or naltrexone-containing products within 28 days prior to Day -1, or history of hypersensitivity or intolerance to naltrexone or bupropion Have donated blood or have had significant blood loss within 90 days prior to Day -1; or have donated plasma within 7 days prior to Day -1 Hemoglobin concentration <11 g/dL at Screening Blood pressure >140/90 mm Hg at Screening or Day -1 Women who are pregnant or trying to become pregnant, have a positive pregnancy test at Screening or Day -1, are currently breast-feeding, or are of childbearing potential (including perimenopausal women who have had a menstrual period within 1 year prior to Day -1) and are not willing to practice effective birth control. Women who are surgically sterile (including bilateral tubal ligation, tubal occlusion, hysterectomy or oophorectomy) are not considered to be of childbearing potential. Drug or alcohol abuse or dependence within 6 months prior to Screening, or positive urine drug screen at Screening or Day -1 Regular daily use of tobacco products, including inhaled tobacco (e.g., cigarettes, cigars, pipes), chewing tobacco or snuff, or nicotine replacement products (including electronic cigarettes or nicotine vaporizers) within 28 days prior to Day -1 Unwilling to refrain from consumption of any citrus products (e.g., whole fruit, juice or products containing orange, grapefruit, or pomelo), alcohol or caffeine/xanthine-containing foods or beverages for 48 hours before study drug intake in each treatment period (Days 1 and 15) until 72 hours postdose (Days 4 and 18) Inability or unwillingness to consume a standardized high-fat breakfast as provided at the study clinic on Days 1 and 15 Inability to comply with all required study procedures and schedule, inability to speak and read English, or unwillingness or inability to give written informed consent Employee or immediate family member of the sponsor (or designee) or study site research staff Use of any investigational drug, device, or procedure within 30 days prior to Day -1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fed Group<br>Reference and test product naltrexone SR/bupropion SR combination trilayer tablets tested in the fed state. | Drug: Reference naltrexone 8 mg SR/bupropion 90 mg SR combination trilayer tablets (2 tablets)<br> <br> * Other names: Contrave;Drug: Test naltrexone 8 mg SR/bupropion 90 mg SR combination trilayer tablets (2 tablets)<br> <br> |
| Active Comparator: Fasted group<br>Reference and test product naltrexone SR/bupropion SR combination trilayer tablets tested in the fasted state. | Drug: Reference naltrexone 8 mg SR/bupropion 90 mg SR combination trilayer tablets (2 tablets)<br> <br> * Other names: Contrave;Drug: Test naltrexone 8 mg SR/bupropion 90 mg SR combination trilayer tablets (2 tablets)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum observed plasma concentration | 0-96 hours post-dose | 
| AUC(0-t) | Area under the plasma concentration-time curve from 0 hour to the time of the last quantifiable concentration | 0-96 hours post-dose | 
| AUC(0-inf) | Area under the plasma concentration-time curve from 0 hour extrapolated to infinity | 0-96 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetic, Obesity, Overweight, Contrave, Antiobesity agents, Antiobesity drugs, Weight loss drug, Bioequivalence