Buprenorphine 8 mg Sublingual Tablets Under Fasting Conditions

Study Overview
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Brief Summary
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The object of this study is to compare the rate and extent of absorption of an investigational formulation of buprenorphine 8 mg sublingual tablets manufactured by Barr Laboratories, Inc. to an equivalent oral dose of the commercially available reference product, Subutex® manufactured by Reckitt Benckiser, following and overnight fast of at least 10 hours.

Detailed Description
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Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA Bioequivalence Statistical Methods

Official Title
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A Single-Dose, 2-Period, 2-Treatment, 2-Way Crossover Bioequivalence Study of Buprenorphine 8 mg Sublingual Tablets Under Fasting Conditions.

Conditions
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Healthy

Intervention / Treatment
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* Drug: Buprenorphine
* Drug: Buprenorphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be a male or non-pregnant, non-breastfeeding female. Subject must be between 18 and 45 years of age (inclusive). Subject's Body Mass Index (BMI) must be between 18 and 30 (inclusive), and subject must weigh a minimum of 50 kg (110 lbs). Female subjects must agree to utilize one of the following forms of contraception from screening through 4 weeks after completion of the study. Approved forms of contraception are abstinence, double barrier, IUD in place at least 30 days prior to study drug administration, vasectomized partner, surgically sterile for at least 6 months, or at least 2 years postmenopausal. Subject must voluntarily consent to participate in this study and provide their written informed consent prior to completion of any study-specific procedures. Subject is willing and able to remain in the study unit for the entire duration of the confinement period and return for all scheduled outpatient visits. Exclusion Criteria: History or presence of any clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results. History or presence of pancreatitis, bowel obstruction, glaucoma, enlargement of the prostate, adrenal disease, hyperthyroidism, or gallbladder disease. Subjects with a history of cholecystectomy for the treatment of gallbladder disease will be excluded. Females taking any oral contraceptives including estrogen and progestin combined pills, progestin-only pills, patch, or vaginal ring within 28 days prior to the first dose of study medication; using injectable contraceptives within 6 months of first dose; or who have ever had progestational hormone implants. Females taking hormone replacement therapy within 60 days prior to the first dose of study medication. Has a clinically significant abnormal finding on the physical exam, medical history, ECG, or clinical laboratory results at screening. History or presence of allergic or adverse response to buprenorphine, naltrexone, or any comparable or similar product. Has been on a significantly abnormal diet during the 4 weeks preceding the first dose of study medication. Has donated blood or plasma within 30 days prior to the first dose of study medication. Has participated in another clinical trial within 30 days prior to the first dose of study medication. Has used any over-the-counter (OTC) medication, including cough and cold preparations, vitamins, and herbal supplements, within 7 days prior to the first dose of study medication. Has used any prescription medication within 14 days prior to the first dose of study medication. Has consumed beverages or food containing alcohol, caffeine/xanthine, or poppy seeds from 48 hours prior to the first dose of study medication or has consumed beverages or foods containing grapefruit from 14 days prior to the first dose of study medication. Has been treated with any known enzyme-altering drugs, such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study medication. Has smoked or used tobacco products within 60 days prior to the first dose of study medication. Has a history of treatment for substance abuse (including alcohol) in the past 5 years. Is a female with a positive pregnancy test result. Has any piercing of the tongue or has a lip piercing within 30 days prior to the first dose of study medication. Has a positive urine screen for drugs of abuse. Has a positive urine alcohol test or ethanol breath test. Has a positive test for or has been treated for hepatitis B, hepatitis C, or HIV.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational Test Product<br>Buprenorphine 8 mg Sublingual Tablets | Drug: Buprenorphine<br>* 8 mg Sublingual Tablets<br>|
| Active Comparator: Reference Listed Drug<br>Subutex® 8 mg Sublingual Tablets | Drug: Buprenorphine<br>* 8 mg Sublingual Tablets<br>* Other names: Subutex®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Buprenorphine. | Bioequivalence based on Buprenorphine Cmax (maximum observed concentration of drug substance in plasma). | Blood samples collected over a 144 hour period. | 
| AUC0-t for Buprenorphine. | Bioequivalence based on Buprenorphine AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration). | Blood samples collected over a 144 hour period. | 
| AUC0-inf for Buprenorphine. | Bioequivalence based on Buprenorphine AUC0-inf (area under the concentration-time curve from time zero to infinity). | Blood samples collected over a 144 hour period. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax for Norbuprenorphine. | Informational comparison of Cmax (maximum observed concentration of drug substance in plasma) values for the metabolite Norbuprenorphine. | Blood samples collected over a 144 hour period. | 
| AUC0-t for Norbuprenorphine. | Informational comparison of AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration) values for the metabolite Norbuprenorphine. | Blood samples collected over a 144 hour period. | 
| AUC0-inf for Norbuprenorphine. | Informational comparison of AUC0-inf (area under the concentration-time curve from time zero to infinity) values for the metabolite Norbuprenorphine. | Blood samples collected over a 144 hour period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioequivalence, Healthy