Induction of Opioid-Dependent Individuals Onto Buprenorphine and Buprenorphine/Naloxone

Indivior

Status and phase: Completed; Phase 2

Conditions: Opioid-related Disorders

Treatments: Drug: Placebo; Drug: Buprenorphine/naloxone film strip; Drug: Buprenorphine soluble film

Study type: Interventional

Funder types: Industry

Identifiers

NCT00637000

RB-US-07-0002

Details and patient eligibility

About

The purpose of this study is to compare the presence, degree, time course and profile of opioid withdrawal symptoms associated with induction onto new formulations of buprenorphine or buprenorphine/naloxone in persons with active opioid dependence. The primary outcome measure is the severity of withdrawal symptoms measured using the Clinical Opiate Withdrawal Scale (COWS). The primary study hypothesis is that neither drug formulation will precipitate an opioid withdrawal syndrome.

Full description

Buprenorphine sublingual and buccal soluble films are being developed to be used for the same indication and over the same buprenorphine dose range as Subutex and Suboxone sublingual tablets in the treatment of opioid dependence. However, only films administered by the sublingual route were evaluated in this study.

The soluble film dosage is expected to provide the following enhancements and potential advantages over the current Subutex and Suboxone product:

• Mitigation against unintentional pediatric exposure by providing child-resistant packaging in unit dose format.
• Improvement in subject convenience and compliance by ensuring rapid disintegration.
• Protection against diversion by providing a dosage form that is very difficult for the subject to remove from the sublingual or buccal mucosa after administration. This provides assurance to the caregiver that the dose has actually been taken appropriately in a supervised setting.
• Provision of a unit dose product format for hospital and institutional use.
• Decreased product damage during shipping as compared to Subutex and Suboxone tablets.

Enrollment: 38 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Subject must:

• Provide written informed consent.
• Have a Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of opioid dependence.
• Be male or female, 18 to 65 years of age, inclusive.
• If female, have a negative pregnancy test during screening and agree to use an acceptable method of birth control.

Exclusion criteria

Subjects must not:

• Have participated in an experimental drug or device study within the last 30 days.
• Be currently (past 30 days from start of screening) engaged in opioid agonist, opioid partial agonist, or opioid antagonist treatment.
• If female, be breast feeding or lactating.
• Have any medical condition that in the opinion of the physician investigator would preclude the subject from completing the study.
• Have any clinically significant non-substance use psychiatric disorder (e.g., schizophrenia).
• Have current suicidal ideation.
• Have a Mini Mental Status Exam score less than 24.
• Have physical dependence on alcohol.
• Have physical dependence on sedative-hypnotics.
• Have active aphthous stomatitis.
• Have active oral herpes.
• Need on-going prescription medications that interact with the P450 3A4 (a member of the cytochrome P450 superfamily of enzymes) system.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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38 participants in 2 patient groups

Buprenorphine soluble film

Experimental group

Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours. Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Treatment:

Drug: Buprenorphine soluble film

Drug: Placebo

Buprenorphine/naloxone soluble film

Experimental group

Description:

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours. Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Treatment:

Drug: Placebo

Drug: Buprenorphine/naloxone film strip