Clinical trial NCT02357901: Treatment Seeking Participants With Opioid Use Disorders Assessing Tolerability of Depot Injections of Buprenorphine
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Assess the Efficacy, Safety, and Tolerability of Multiple Subcutaneous Injections of Depot Buprenorphine (RBP-6000 [100 mg and 300 mg]) Over 24 Weeks in Treatment-Seeking Subjects With Opioid Use Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Opioid Dependence
Opioid Related Disorders
Lead sponsor: Indivior Inc.
Sponsor class: INDUSTRY
First posted: 2015-02-06
Enrollment: 665
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo controlled, multicenter study in male and female participants who are seeking treatment for opioid use disorder.

Detailed description: After completing an up to 2-week screening period, subjects entered an open-label run-in induction phase with SUBOXONE (buprenorphine/naloxone) sublingual film for 3 days followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information.

This is a 24-week non-residential study with participants being randomized after meeting randomization criteria. On Day 1 and Day 29 (± 2 days) participants will receive subcutaneous injections of 300 mg RBP-6000 or placebo. Thereafter, participants will receive 4 injections (once every 28 days ± 2 days) of either 300 mg or 100 mg RBP-6000 doses or placebo.

Eligibility criteria: Inclusion Criteria:

* Currently meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for moderate or severe opioid use disorder
* By medical history has met DSM-5 criteria for moderate or severe opioid use disorder for the 3 months immediately prior to signing the informed consent form
* Is seeking medication-assisted treatment for opioid use disorder
* Is an appropriate candidate for opioid partial-agonist medication-assisted treatment in the opinion of the investigator or medically responsible physician
* Body mass index (BMI) of ≥ 18.0 to ≤ 35.0 kg/m\^2

Exclusion Criteria:

* Current diagnosis other than opioid use disorder requiring chronic opioid treatment
* Current substance use disorder as defined by DSM-5 criteria with regard to any substances other than opioids, cocaine, cannabis, tobacco, or alcohol.
* Positive urine drug screen (UDS) result at screening for cocaine or cannabis AND meets DSM-5 criteria for either moderate or severe cocaine or cannabis use disorder, respectively
* Meets DSM-5 criteria for moderate or severe alcohol use disorder
* Received medication-assisted treatment for opioid use disorder (e.g., methadone, buprenorphine) in the 90 days prior to providing written informed consent

Primary outcomes:
measure: Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids Combined With Self-Reports Negative for Illicit Opioid Use Collected From Week 5 Through Week 24
timeFrame: Weekly from Weeks 5-24
Secondary outcomes:
measure: Percentage of Participants Considered A Treatment Success
timeFrame: Weeks 5-24
measure: Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24
timeFrame: Weekly from Weeks 5-24
measure: Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24
timeFrame: Weekly from Weeks 5-24
measure: Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) Prior to Injections From Week 5 Through Week 24 Analyzed by Mixed Model for Repeated Measures
timeFrame: Baseline: Day 1 (prior to dosing), Weeks 5-24
measure: Participants Who Complete the Week 24 Visit ("Completers")
timeFrame: Week 24
measure: Participants Who Are Abstinent at Week 24
timeFrame: Week 24
measure: Change From Baseline in the Clinical Global Impression - Improvement Scale (CGI-I) Prior to Injections From Week 5 Through Week 24 Analyzed by Mixed Model for Repeated Measures
timeFrame: Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169
measure: Change From Baseline in the Clinical Global Impression - Severity Scale (CGI-S) Prior to Injections From Week 5 Through Week 24 Analyzed by Mixed Model for Repeated Measures
timeFrame: Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169
measure: Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Through Week 24 Analyzed by Mixed Model for Repeated Measures
timeFrame: Baseline: Day 1 (prior to dosing), Baseline: Day 1 (prior to dosing), Days 2, 8, 5, 22, 29, 30, 36, 43, 50, 57, 58, 64, 71, 78, 85, 86, 92, 99, 106, 113, 114, 120, 127, 134, 141, 142, 148, 155, 162, 169
measure: Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Through Week 24 Analyzed by Mixed Model for Repeated Measures
timeFrame: Baseline: Day 1 (prior to dosing), Baseline: Day 1 (prior to dosing), Days 2, 8, 5, 22, 29, 30, 36, 43, 50, 57, 58, 64, 71, 78, 85, 86, 92, 99, 106, 113, 114, 120, 127, 134, 141, 142, 148, 155, 162, 169
measure: Total Number of Weeks of Abstinence as Assessed From Urine Samples Negative for Opioids Combined With Self-Reports Negative for Illicit Opioid Use Collected From Week 5 Through Week 24
timeFrame: Weeks 5 through 24
measure: Participants With Adverse Events During the Treatment Period
timeFrame: Day 1 through Week 24
measure: Worst Injection Site Pain From Injections 1-6 as Measured by Participant-Reported Visual Analog Scale (VAS)
timeFrame: Days 1, 29, 57, 85, 113, 141
measure: Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24
timeFrame: Weekly - Week 2 through Week 24
Other outcomes:
Locations:
city: Haleyville
country: United States
facility: Haleyville Clinical Research
state: Alabama
city: Hamilton
country: United States
facility: Boyett Health Services
state: Alabama
city: Little Rock
country: United States
facility: Woodland International Research Group
state: Arkansas
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network
state: California
city: Glendale
country: United States
facility: Behavioral Research Specialists
state: California
city: National City
country: United States
facility: Synergy Clinical Research Center
state: California
city: Oceanside
country: United States
facility: North County Clinical Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Francisco
country: United States
facility: Care Practice
state: California
city: Thousand Oaks
country: United States
facility: Southern California Research
state: California
city: Jacksonville
country: United States
facility: Amit Vijapura
state: Florida
city: Lakeland
country: United States
facility: Meridien Research
state: Florida
city: Lauderhill
country: United States
facility: Innovative Clinical Research
state: Florida
city: Maitland
country: United States
facility: Florida Clinical Research Center
state: Florida
city: Maitland
country: United States
facility: Try Research
state: Florida
city: North Miami
country: United States
facility: Scientific Clinical Research
state: Florida
city: Oakland Park
country: United States
facility: Research Centers of America
state: Florida
city: Schaumburg
country: United States
facility: Behavioral Health Care Associates
state: Illinois
city: Prairie Village
country: United States
facility: Phoenix Medical Research
state: Kansas
city: New Orleans
country: United States
facility: Louisiana Research Associates
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana Clinical Research
state: Louisiana
city: Fall River
country: United States
facility: Stanley Street Treatment and Resources
state: Massachusetts
city: Watertown
country: United States
facility: Adams Clinical Trials
state: Massachusetts
city: Flowood
country: United States
facility: Precise Research Centers, Inc.
state: Mississippi
city: Saint Louis
country: United States
facility: St Louis Clinical Trials
state: Missouri
city: Las Vegas
country: United States
facility: Altea Research
state: Nevada
city: Berlin
country: United States
facility: Comprehensive Clinical Research
state: New Jersey
city: Canton
country: United States
facility: Neuro-behavioral Clinical Research
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Garfield Heights
country: United States
facility: Charak Clinical Research Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Clinical Research Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Pahl Pharmaceutical Professionals
state: Oklahoma
city: Portland
country: United States
facility: CODA
state: Oregon
city: Altoona
country: United States
facility: Tipton Medical and Diagnostic Center aka Clinical Research Associates of Central PA
state: Pennsylvania
city: Philadelphia
country: United States
facility: UPenn Treatment Research Center
state: Pennsylvania
city: Charleston
country: United States
facility: Carolina Clinical Trials
state: South Carolina
city: Dallas
country: United States
facility: Pillar Clinical Research
state: Texas
city: DeSoto
country: United States
facility: InSite Clinical Research
state: Texas
Study officials:
affiliation: Indivior Inc.
name: Director Global Clinical Development
role: STUDY_DIRECTOR
References:
citation: 2022 Poster Abstracts. J Addict Med. 2022 Sep-Oct 01;16(5):e284-e347. doi: 10.1097/ADM.0000000000001068. No abstract available.
citation: Craft WH, Tegge AN, Keith DR, Shin H, Williams J, Athamneh LN, Stein JS, Chilcoat HD, Le Moigne A, DeVeaugh-Geiss A, Bickel WK. Recovery from opioid use disorder: A 4-year post-clinical trial outcomes study. Drug Alcohol Depend. 2022 May 1;234:109389. doi: 10.1016/j.drugalcdep.2022.109389. Epub 2022 Mar 9.
citation: Boyett B, Wiest K, McLeod LD, Nelson LM, Bickel WK, Learned SM, Heidbreder C, Fudala PJ, Le Moigne A, Zhao Y. Assessment of craving in opioid use disorder: Psychometric evaluation and predictive validity of the opioid craving VAS. Drug Alcohol Depend. 2021 Dec 1;229(Pt B):109057. doi: 10.1016/j.drugalcdep.2021.109057. Epub 2021 Sep 24.
citation: Kranzler HR, Lynch KG, Crist RC, Hartwell E, Le Moigne A, Laffont CM, Andorn AC. A Delta-Opioid Receptor Gene Polymorphism Moderates the Therapeutic Response to Extended-Release Buprenorphine in Opioid Use Disorder. Int J Neuropsychopharmacol. 2021 Feb 15;24(2):89-96. doi: 10.1093/ijnp/pyaa069.
citation: Haight BR, Learned SM, Laffont CM, Fudala PJ, Zhao Y, Garofalo AS, Greenwald MK, Nadipelli VR, Ling W, Heidbreder C; RB-US-13-0001 Study Investigators. Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2019 Feb 23;393(10173):778-790. doi: 10.1016/S0140-6736(18)32259-1. Epub 2019 Feb 18.