Multiple Dose Pharmacokinetics Depot Buprenorphine in Opioid-Dependent Subjects

This study is currently recruiting participants.
Verified December 2013 by Reckitt Benckiser Pharmaceuticals Inc.
Sponsor:
Information provided by (Responsible Party):
Reckitt Benckiser Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01738503
First received: November 28, 2012
Last updated: January 15, 2014
Last verified: December 2013
  Purpose

This is an open-label study in treatment seeking opioid-dependent subjects for safety, tolerability, pharmacokinetics, efficacy markers, and opioid receptor availability of subcutaneous injections of depot buprenorphine after induction and stabilization of treatment seeking subjects onto Subutex.


Condition Intervention Phase
Opioid Related Disorder
Drug: RBP-6000
Drug: Subutex
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics, Efficacy Markers, and Opioid Receptor Availability of Subcutaneous Injections of Depot Buprenorphine (RBP-6000) in Treatment Seeking Opioid-Dependent Subjects

Resource links provided by NLM:


Further study details as provided by Reckitt Benckiser Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Compare the steady state PK of buprenorphine and norbuprenorphine after SC doses of RBP-6000 relative to the corresponding SUBUTEX doses [ Time Frame: Days -13 to -1 (Subutex treatment), Days 1-113 (RBP-6000 treatment) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline To Day 113 in the Clinical Opiate Withdrawal Scale (COWS) [ Time Frame: Day 1 (pre-treatment), Day 113 ] [ Designated as safety issue: No ]
  • Change from Baseline To Day 113 in the Subjective Opiate Withdrawal Scale (SOWS) [ Time Frame: Day 1 (pre-treatment), Day 113 ] [ Designated as safety issue: No ]
  • Change from Baseline To Day 113 in the Opioid Craving Visual Analog Scale (VAS) [ Time Frame: Day 1 (pre-treatment), Day 113 ] [ Designated as safety issue: No ]
  • Change from Baseline To Day 113 in the Clinical Global Impression Total Scores. [ Time Frame: Day 1 (pre-treatment), Day 113 ] [ Designated as safety issue: No ]
    The total of the Clinical Global Impression - Severity scale (CGIS) and the Clinical Global Impression - Improvement scale (CGI-I) scores .

  • Change from Baseline To Day 113 in the Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Day 1 (pre-treatment), Day 113 ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: November 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: (8 mg) RBP-6000: 50 mg
Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.
Drug: RBP-6000
18% Buprenorphine Sterile Solution for subcutaneous (SC) injection using the ATRIGEL® Delivery System. Each injection of RBP-6000 is separated by a minimum of 28 days and will be given on alternate sides of the participant's abdomen.
Other Name: buprenorphine
Drug: Subutex
Participants were inducted and stabilized (over a 14-day period) on SUBUTEX at doses of 8 mg, 12 mg, 14 mg, or 8-24 mg. Tablets are placed under the tongue until dissolved.
Other Name: Buprenorphine
Experimental: (12 mg) RBP-6000: 100 mg
Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals
Drug: RBP-6000
18% Buprenorphine Sterile Solution for subcutaneous (SC) injection using the ATRIGEL® Delivery System. Each injection of RBP-6000 is separated by a minimum of 28 days and will be given on alternate sides of the participant's abdomen.
Other Name: buprenorphine
Drug: Subutex
Participants were inducted and stabilized (over a 14-day period) on SUBUTEX at doses of 8 mg, 12 mg, 14 mg, or 8-24 mg. Tablets are placed under the tongue until dissolved.
Other Name: Buprenorphine
Experimental: (24 mg) RBP-6000: 200 mg

Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals.

Participants who receive RBP-6000 containing 200 mg buprenorphine and reach Day 112 (and have received all 4 planned SC injections) will have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants will remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.

Drug: RBP-6000
18% Buprenorphine Sterile Solution for subcutaneous (SC) injection using the ATRIGEL® Delivery System. Each injection of RBP-6000 is separated by a minimum of 28 days and will be given on alternate sides of the participant's abdomen.
Other Name: buprenorphine
Drug: Subutex
Participants were inducted and stabilized (over a 14-day period) on SUBUTEX at doses of 8 mg, 12 mg, 14 mg, or 8-24 mg. Tablets are placed under the tongue until dissolved.
Other Name: Buprenorphine
Experimental: (8 mg) RBP-6000: 100 mg
Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.
Drug: RBP-6000
18% Buprenorphine Sterile Solution for subcutaneous (SC) injection using the ATRIGEL® Delivery System. Each injection of RBP-6000 is separated by a minimum of 28 days and will be given on alternate sides of the participant's abdomen.
Other Name: buprenorphine
Drug: Subutex
Participants were inducted and stabilized (over a 14-day period) on SUBUTEX at doses of 8 mg, 12 mg, 14 mg, or 8-24 mg. Tablets are placed under the tongue until dissolved.
Other Name: Buprenorphine
Experimental: (14 mg) RBP-6000: 200 mg

Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals.

Participants who receive RBP-6000 containing 200 mg buprenorphine and reach Day 112 (and have received all 4 planned SC injections) will have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants will remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.

Drug: RBP-6000
18% Buprenorphine Sterile Solution for subcutaneous (SC) injection using the ATRIGEL® Delivery System. Each injection of RBP-6000 is separated by a minimum of 28 days and will be given on alternate sides of the participant's abdomen.
Other Name: buprenorphine
Drug: Subutex
Participants were inducted and stabilized (over a 14-day period) on SUBUTEX at doses of 8 mg, 12 mg, 14 mg, or 8-24 mg. Tablets are placed under the tongue until dissolved.
Other Name: Buprenorphine
Experimental: (8-24 mg) RBP-6000: 300 mg
Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals.
Drug: RBP-6000
18% Buprenorphine Sterile Solution for subcutaneous (SC) injection using the ATRIGEL® Delivery System. Each injection of RBP-6000 is separated by a minimum of 28 days and will be given on alternate sides of the participant's abdomen.
Other Name: buprenorphine
Drug: Subutex
Participants were inducted and stabilized (over a 14-day period) on SUBUTEX at doses of 8 mg, 12 mg, 14 mg, or 8-24 mg. Tablets are placed under the tongue until dissolved.
Other Name: Buprenorphine

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects
  • Agree not to take any buprenorphine products other than those administered for the current study throughout participation in the study
  • Body mass index (BMI) of >18.0 to < 33.0 kg/m

Exclusion Criteria:

  • Participants with a current diagnosis requiring chronic opioid treatment
  • Participants with a history of risk factors of Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) or an ECG demonstrating a Fridericia's corrected QT interval (QTcF) >450 msec in males and QTcF > 470 in females at screening
  • Abuse of buprenorphine or use of buprenorphine within 14 days of informed consent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01738503

Contacts
Contact: Heather D Sutton 804-423-8961

Locations
United States, Kansas
Vince and Associates Clinical Research Recruiting
Overland Park, Kansas, United States, 66212
Contact: Bradley D Vince, DO    913-696-1601      
Principal Investigator: Bradley D. Vince, DO         
Sub-Investigator: Steven G Hull, MD         
Sponsors and Collaborators
Reckitt Benckiser Pharmaceuticals Inc.
Investigators
Principal Investigator: Bradley D Vince, DO Vince and Associates Clinical Research
  More Information

No publications provided

Responsible Party: Reckitt Benckiser Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01738503     History of Changes
Other Study ID Numbers: RB-US-12-0005
Study First Received: November 28, 2012
Last Updated: January 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Reckitt Benckiser Pharmaceuticals Inc.:
Opioid Dependence, Buprenorphine, Depot, SUBUTEX, RBP-6000

Additional relevant MeSH terms:
Narcotic Antagonists
Narcotics
Opioid-Related Disorders
Substance-Related Disorders
Mental Disorders
Buprenorphine
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants

ClinicalTrials.gov processed this record on April 17, 2014