Pharmacokinetics, Safety, and Tolerability of Depot Buprenorphine at Three Different Molecular Weights in Treatment-Seeking Subjects With Opioid Use Disorder

Sponsor

Indivior Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02559973

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

7.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a single-center, randomized, open-label, single-dose, parallel-group study which will enroll and randomize approximately 48 subjects (to achieve 36 completers) with opioid use disorder (OUD) who are seeking treatment for OUD. The study includes both a Residential (Inpatient) and Non-Residential (Outpatient) Period.

Condition or Disease	Intervention/Treatment	Phase
Opioid Use Disorder	Drug: RBP-6000 Drug: SUBOXONE Sublingual Film	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

47 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Single-Center, Randomized, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Depot Buprenorphine (RBP-6000) Using Poly (DL-lactide-co-glycolide) Polymer of Two Different Molecular Weights (Low and High Molecular Weights as Test Treatments) in Comparison to Intermediate Molecular Weight (Reference Treatment) in Treatment-Seeking Subjects With Opioid Use Disorder

Study Start Date :

Sep 1, 2015

Actual Primary Completion Date :

Feb 1, 2016

Actual Study Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RBP-6000 - Light MW Single subcutaneous injection of RBP-6000 (buprenorphine) 300 mg, formulated with a light molecular weight (MW) polymer.	Drug: RBP-6000 RBP-6000 uses buprenorphine in the ATRIGEL Delivery System. The single-syringe is prefilled with RBP-6000 containing 300 mg buprenorphine. Other Names: buprenorphine Drug: SUBOXONE Sublingual Film Subjects will be dose-stabilized on SUBOXONE sublingual film prior to administration of RBP-6000. SUBOXONE sublingual film will be administered beginning after the subject is experiencing signs and symptoms of withdrawal on Day -8 and continue until Day -1. Other Names: buprenorphine HCl and naloxone HCl dihydrate
Experimental: RBP-6000 - Heavy MW Single subcutaneous injection of RBP-6000 (buprenorphine) 300 mg, formulated with a heavy molecular weight (MW) polymer.	Drug: RBP-6000 RBP-6000 uses buprenorphine in the ATRIGEL Delivery System. The single-syringe is prefilled with RBP-6000 containing 300 mg buprenorphine. Other Names: buprenorphine Drug: SUBOXONE Sublingual Film Subjects will be dose-stabilized on SUBOXONE sublingual film prior to administration of RBP-6000. SUBOXONE sublingual film will be administered beginning after the subject is experiencing signs and symptoms of withdrawal on Day -8 and continue until Day -1. Other Names: buprenorphine HCl and naloxone HCl dihydrate
Active Comparator: RBP-6000 - Intermediate MW Single subcutaneous injection of RBP-6000 (buprenorphine) 300 mg, formulated with an intermediate molecular weight (MW) polymer (reference).	Drug: RBP-6000 RBP-6000 uses buprenorphine in the ATRIGEL Delivery System. The single-syringe is prefilled with RBP-6000 containing 300 mg buprenorphine. Other Names: buprenorphine Drug: SUBOXONE Sublingual Film Subjects will be dose-stabilized on SUBOXONE sublingual film prior to administration of RBP-6000. SUBOXONE sublingual film will be administered beginning after the subject is experiencing signs and symptoms of withdrawal on Day -8 and continue until Day -1. Other Names: buprenorphine HCl and naloxone HCl dihydrate

Arm

Intervention/Treatment

Experimental: RBP-6000 - Light MW

Single subcutaneous injection of RBP-6000 (buprenorphine) 300 mg, formulated with a light molecular weight (MW) polymer.

Drug: RBP-6000

RBP-6000 uses buprenorphine in the ATRIGEL Delivery System. The single-syringe is prefilled with RBP-6000 containing 300 mg buprenorphine.

Other Names:

buprenorphine

Drug: SUBOXONE Sublingual Film

Subjects will be dose-stabilized on SUBOXONE sublingual film prior to administration of RBP-6000. SUBOXONE sublingual film will be administered beginning after the subject is experiencing signs and symptoms of withdrawal on Day -8 and continue until Day -1.

Other Names:

buprenorphine HCl and naloxone HCl dihydrate

Experimental: RBP-6000 - Heavy MW

Single subcutaneous injection of RBP-6000 (buprenorphine) 300 mg, formulated with a heavy molecular weight (MW) polymer.

Drug: RBP-6000

RBP-6000 uses buprenorphine in the ATRIGEL Delivery System. The single-syringe is prefilled with RBP-6000 containing 300 mg buprenorphine.

Other Names:

buprenorphine

Drug: SUBOXONE Sublingual Film

Other Names:

buprenorphine HCl and naloxone HCl dihydrate

Active Comparator: RBP-6000 - Intermediate MW

Single subcutaneous injection of RBP-6000 (buprenorphine) 300 mg, formulated with an intermediate molecular weight (MW) polymer (reference).

Drug: RBP-6000

RBP-6000 uses buprenorphine in the ATRIGEL Delivery System. The single-syringe is prefilled with RBP-6000 containing 300 mg buprenorphine.

Other Names:

buprenorphine

Drug: SUBOXONE Sublingual Film

Other Names:

buprenorphine HCl and naloxone HCl dihydrate

Outcome Measures

Primary Outcome Measures

Area Under the Concentration-Time Curve from Study Day 1 to Day 29 (AUC0-28days) of Buprenorphine [Day 1 to Day 29]
Relative bioavailability will be assessed using AUC0-28days.
Maximum Observed Plasma Concentration (Cmax) of Buprenorphine [Day 1 to Day 57]
Relative bioavailability will also be assessed using Cmax

Secondary Outcome Measures

Area Under the Concentration-Time Curve from Study Day 1 to Day 29 (AUC0-28days) of Norbuprenorphine [Day 1 to Day 29]
Maximum Observed Plasma Concentration (Cmax) of Norbuprenorphine [Day 1 to Day 57]
Participants with Treatment-Emergent Adverse Events [Day 1 to Day 57]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Currently meets DSM-5 criteria for moderate or severe opioid use disorder (OUD)
Is seeking treatment for OUD
Body mass index: ≥ 18.0 to ≤ 35.0 kg/m^2
Females: Female individuals of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to informed consent) must have a negative serum pregnancy test prior to enrollment and must agree to use a medically acceptable means of contraception from Screening through at least 6 months after the last dose of Investigational Medicinal Product (IMP).
Males: Male individuals with female partners of child-bearing potential must agree to use medically acceptable contraception after signing the informed consent form through at least 6 months after the last dose of IMP. Male individuals must also agree not to donate sperm during the study and for 6 months after receiving the last dose of IMP.
Have a normal electrocardiogram (ECG) or ECG with no clinically significant findings in the opinion of the Investigator or medically qualified sub-investigator at Screening and through pre-dose on Day 1.
Agree not to take any buprenorphine-containing products, other than those administered for the current study, throughout the duration of the study.
Willing to adhere to study procedures and provide written informed consent prior to start of any study procedures.

Exclusion Criteria:

Current diagnosis, other than OUD, requiring chronic opioid treatment.
Pregnant or lactating females.
Have an ECG demonstrating a corrected QT interval using Fridericia's calculation (QTcF) > 450 msec in males and QTcF > 470 msec in females upon admission to the residential facility or prior to administration of RBP-6000.
Currently meet the criteria for diagnosis of moderate or severe substance use disorder, by DSM-5 criteria, for any substances other than opioids, and/or tobacco.
Had a significant traumatic injury, major surgery, or open biopsy within the 4 weeks prior to signing the informed consent form.
Used buprenorphine-containing products within the 14 days prior to signing the informed consent form.
Have a history of suicidal ideation within the 30 days prior to signing the informed consent form or prior to study drug administration
Have a history or presence of allergic or adverse response (including rash or anaphylaxis) to buprenorphine, naloxone, methadone, or the ATRIGEL Delivery System.
Individuals who have a positive urine drug screen (UDS) prior to admission to the residential facility for barbiturates, benzodiazepines, buprenorphine, or methadone.