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Safety and Tolerability Study of Depot Buprenorphine in Treatment Seeking Subjects With Opioid Use Disorder

Primary Purpose

Opioid Use Disorder, Opioid-related Disorders

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

SUBOXONE sublingual film

RBP-6000

About this trial

This is an interventional treatment trial for Opioid Use Disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

De novo subjects:

Seeking treatment for opioid use disorder (OUD) and for the previous 3 months meet the Diagnostic and Statistical Manual 5 (DSM-5) criteria for moderate or severe OUD
Appropriate candidate for opioid partial-agonist treatment
BMI between 18 and 35, inclusive

Roll-over subjects:

Completed RB-US-13-0001

Exclusion Criteria:

De novo subjects:

Current diagnosis, other than OUD, requiring chronic opioid treatment
Current substance use disorder with regard to substances other than opioids, cocaine, cannabis, tobacco or alcohol
Received medication-assisted treatment for OUD in the 90 days prior to informed consent
Use (within past 30 days prior to informed consent) or positive urine drug screen (UDS) at screening for barbiturates, benzodiazepines,methadone or buprenorphine
Treatment for OUD required by court order
History of recent suicidal ideation or attempt

Roll over subjects:

Experienced major protocol deviations or adverse events in RB-US-13-0001 which could potentially compromise subject safety
Discontinued early from study RB-US-13-0001

Sites / Locations

Haleyville Clinical Research
Boyett Health Services
Woodland International Research Group
Collaborative Neuroscience Network
Behavioral Research Specialists
Synergy Clinical Research Center
Pacific Research Partners
North County Clinical Research
Neuropsychiatric Research Center of Orange County
Artemis Institute for Clinical Research
Amit Vijapura
Sarkis Clinical Trials
Meridien Research
Innovative Clinical Research
Florida Clinical Research Center
Try Research
Scientific Clinical Research
Research Centers of America
Atlanta Institute of Medicine and Research
Phoenix Medical Research
Louisiana Research Associates
Louisiana Clinical Research
Stanley Street Treatment and Resources
Adams Clinical Trials
Precise Research Centers, Inc.
St Louis Clinical Trials
Altea Research
Comprehensive Clinical Research
Center for Emotional Fitness
The Medical Research Network, LLC
Neuro-behavioral Clinical Research
Midwest Clinical Research Center
Charak Clinical Research Center
Oklahoma Clinical Research Center
Pahl Pharmaceutical Professionals
CODA
Tipton Medical and Diagnostic Center aka Clinical Research Associates of Central PA
UPenn Treatment Research Center
Carolina Clinical Trials
Pillar Clinical Research
InSite Clinical Research
Aspen Clinical Research, LLC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Roll-over Subjects

De Novo Subjects

Arm Description

Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.

Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.

Outcomes

Primary Outcome Measures

Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period

TEAE=any untoward medical occurrence that develops or worsens in severity after dispensation of the study drug and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= a marked limitation in activity. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent one of the outcomes listed in this definition.

Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs

Vital signs include systolic blood pressure (mmHg) diastolic blood pressure (mmHg) respiratory rate (breaths/minute) weight (kg) body mass index (kg/m^2) waist-to-hip ratio Baseline is defined as the last non-missing value prior to subcutaneous injection of RBP-6000 on Day 1.

Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period

The C-SSRS asks questions of study participants regarding whether they had suicidal ideation and/or suicidal behavior since the last visit using the electronic version of the scale. Only the most severe assessment is reported in this summary. Participants who experienced suicidal ideation and suicidal behavior are only summarized in the suicidal behavior since behavior is more severe than ideation. C-SSRS baseline version was completed during the screening visit. C-SSRS 'since-last-visit' version was completed weekly for the first month and at least every month until the end of the study. Shift table category titles are structured as: baseline category/treatment category. The category 'No Suicidal Ideation or Behaviour' has been abbreviated as 'No Suicidal I or B'.

Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS)

Injection site pain as measured by participant-reported VAS. The participant-reported VAS for injection site pain was measured on a 100 mm scale with 'no pain' at 0 mm and 'strongest pain ever' at 100 mm (total scale of 0-100). Participants marked where along the scale reflected their localized injection pain. The injection site pain VAS scores were obtained (after the completion of the injection) within 1 minute and at 5, 10, 15, 30 and 60 minutes (+- 5 minutes). The timing of the injection site pain VAS should have been measured from the end of the injection. Data represents the worst pain recorded for each participant across all injections and all VAS records. The mean value is presented. De Novo subjects were given injections on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281 and 309. Roll-over subjects were given injections on Days 1, 29, 57, 85, 113, 141.

Secondary Outcome Measures

Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) at End of Study (Weeks 25 and 49)

COWS is an 11-item instrument used to assess signs and symptoms of opioid withdrawal. The score is the sum of the responses for a total range of 0-48. The COWS is commonly used by clinicians treating patients with buprenorphine to monitor the severity of withdrawal. COWS scores below 5 are considered not indicative of withdrawal. Scores from 5 to 12 are considered mild withdrawal; from 13 to 24 moderate withdrawal; 25 to 36 moderately severe withdrawal, and 37-48 severe withdrawal. Negative change from baseline values indicate a lessening of withdrawal symptoms. Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. Baseline value is reported as an observed actual value. Weeks 25 and 49 represent change from baseline values.

Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) at End of Study (Weeks 25 and 49)

The Subjective Opiate Withdrawal Scale (SOWS) contains 16 symptoms whose intensity the participant rates on a scale of 0 (not at all) to 4 (extremely) for a full scale of 0 (no withdrawal symptoms) to 64 (extreme withdrawal symptoms). Negative change from baseline values indicate a lessening of withdrawal symptoms. Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. Baseline value is reported as an observed actual value. Weeks 25 and 49 represent change from baseline values.

Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) at End of Study (Weeks 25 and 49)

The opioid craving scale was a 100 mm scale with 'no craving' indicated by 0 mm and 'strongest craving ever' indicated by 100 mm. Participants marked where along the scale reflected their craving for opioids. Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. Baseline value is reported as an observed actual value. Weeks 25 and 49 represent change from baseline values.

Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49)

Participants' self-reported illicit opioid drug use from the timeline followback (TLFB) interview and results from the urine drug screens (UDS) for opioids were combined into a single endpoint. Opioids assessed included codeine, hydrocodone, hydromorphone, methadone, morphine, opiates, oxycodone, and oxymorphone (by UDS) and amphetamine/methadone, buprenorphine, methadone, and opioids in the TLFB. Data represent the count of participants at various percentage abstinence levels. Abstinence was defined as urine samples being negative for opioids AND negative self-reports (obtained from Timeline Followback (TLFB) interviews) for illicit opioid use. The endpoint was based on visits in which paired urine samples and self-reports were expected for each subject as specified in the schedule of events. All missing reports for opioids were considered nonnegative.

Full Information

NCT ID

NCT02510014

First Posted

July 20, 2015

Last Updated

March 27, 2018

Sponsor

Indivior Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02510014

Brief Title

Safety and Tolerability Study of Depot Buprenorphine in Treatment Seeking Subjects With Opioid Use Disorder

Official Title

An Open-Label, Long-Term Safety and Tolerability Study of Depot Buprenorphine (RBP-6000) in Treatment-Seeking Subjects With Opioid Use Disorder

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Completed

Study Start Date

July 27, 2015 (Actual)

Primary Completion Date

January 31, 2017 (Actual)

Study Completion Date

January 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Indivior Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

A multi-center, open-label, long-term safety study in which approximately 600 subjects diagnosed with opioid use disorder will be enrolled. Following a screening period, all subjects will receive run in SUBOXONE sublingual film followed by an initial injection of open-label high dose (300 mg) RBP-6000. The RBP-6000 monthly injection dose can be adjusted to low dose (100 mg), and back to high dose, based on the medical judgment of the Investigator. Subjects will participate in the study for either 6 or 12 months.

Detailed Description

Approximately 600 subjects diagnosed with opioid use disorder will be enrolled; approximately 300 subjects who completed the randomized,double-blind, placebo-controlled study NCT02357901 (RB-US-13-0001) ('roll-over' participants), and approximately 300 subjects who did not participate in study RB-US-13-0001 ('de novo' participants). Following informed consent and completion of screening procedures, all subjects will receive SUBOXONE sublingual film, titrated to response. After 4-14 days of SUBOXONE sublingual film treatment, subjects will be evaluated for enrollment into the study. Eligible subjects will receive 300 mg RBP-6000 as an initial dose, followed by monthly injections of 100 mg or 300 mg RBP-6000, based on the medical judgment of the investigator. Subjects who participated in study RB-US-13-0001 ('roll-over' participants) will receive monthly injections for up to 6 months. Subjects who did not participate in study RB-US-13-0001 ('de novo' participants) will receive monthly injections for up to12 months. At all injection visits continuous electrocardiogram recordings and pulse oximetry will be collected prior to injection and at least 4 hours after injection. Subjects will return to the clinic every 1-4 weeks for laboratory tests, complete study questionnaires, adverse event and injection site assessments.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Opioid Use Disorder, Opioid-related Disorders

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

775 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Roll-over Subjects

Arm Type

Experimental

Arm Description

Arm Title

De Novo Subjects

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

SUBOXONE sublingual film

Other Intervention Name(s)

SUBOXONE, buprenorphine

Intervention Description

SUBOXONE (buprenorphine sublingual film) is used for induction therapy on Days -14 to -12. Participants then complete a 4-to-11 day sublingual film dose adjustment at doses ranging from 8 mg to 24 mg sublingual film prior to starting the Treatment Period.

Intervention Type

Drug

Intervention Name(s)

RBP-6000

Other Intervention Name(s)

Atrigel buprenorphine

Intervention Description

Injections administered subcutaneously every 28 days on alternate sides of participant's abdomen starting at 300 mg. Subsequent doses of RBP-6000 could be adjusted down to 100 mg with the possibility of adjusting back up to 300 mg based on the medical judgment of the investigator. De novo subjects receive up to 12 injections and roll-over subjects receive up to 6 injections.

Primary Outcome Measure Information:

Title

Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period

Description

Time Frame

Day 1 to Week 49 (De novo arm); Day 1 to Week 25 (Roll-over arm)

Title

Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs

Description

Time Frame

Baseline (Day 1 predose) End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)

Title

Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period

Description

Time Frame

Baseline (Screening visit, days -21 to -15), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)

Title

Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS)

Description

Time Frame

De Novo Subjects: Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281 and 309 Roll-over Subjects: Days 1, 29, 57, 85, 113, 141

Secondary Outcome Measure Information:

Title

Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) at End of Study (Weeks 25 and 49)

Description

Time Frame

Baseline (Day 1 predose), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)

Title

Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) at End of Study (Weeks 25 and 49)

Description

Time Frame

Baseline (Day 1 predose), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)

Title

Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) at End of Study (Weeks 25 and 49)

Description

Time Frame

Baseline (Day 1 predose), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)

Title

Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49)

Description

Time Frame

Weekly during Month 1, Every other week from Month 2-6, Monthly from Month 7-12. De novo arm stopped at Week 49. Roll-over arm stopped at Week 25

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: De novo subjects: Seeking treatment for opioid use disorder (OUD) and for the previous 3 months meet the Diagnostic and Statistical Manual 5 (DSM-5) criteria for moderate or severe OUD Appropriate candidate for opioid partial-agonist treatment BMI between 18 and 35, inclusive Roll-over subjects: Completed RB-US-13-0001 Exclusion Criteria: De novo subjects: Current diagnosis, other than OUD, requiring chronic opioid treatment Current substance use disorder with regard to substances other than opioids, cocaine, cannabis, tobacco or alcohol Received medication-assisted treatment for OUD in the 90 days prior to informed consent Use (within past 30 days prior to informed consent) or positive urine drug screen (UDS) at screening for barbiturates, benzodiazepines,methadone or buprenorphine Treatment for OUD required by court order History of recent suicidal ideation or attempt Roll over subjects: Experienced major protocol deviations or adverse events in RB-US-13-0001 which could potentially compromise subject safety Discontinued early from study RB-US-13-0001

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Global Director Clinical Development

Organizational Affiliation

Indivior Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Haleyville Clinical Research

City

Haleyville

State/Province

Alabama

ZIP/Postal Code

35565

Country

United States

Facility Name

Boyett Health Services

City

Hamilton

State/Province

Alabama

ZIP/Postal Code

35570

Country

United States

Facility Name

Woodland International Research Group

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72211

Country

United States

Facility Name

Collaborative Neuroscience Network

City

Garden Grove

State/Province

California

ZIP/Postal Code

92845

Country

United States

Facility Name

Behavioral Research Specialists

City

Glendale

State/Province

California

ZIP/Postal Code

91206

Country

United States

Facility Name

Synergy Clinical Research Center

City

National City

State/Province

California

ZIP/Postal Code

91950

Country

United States

Facility Name

Pacific Research Partners

City

Oakland

State/Province

California

ZIP/Postal Code

94612

Country

United States

Facility Name

North County Clinical Research

City

Oceanside

State/Province

California

ZIP/Postal Code

92056

Country

United States

Facility Name

Neuropsychiatric Research Center of Orange County

City

Orange

State/Province

California

ZIP/Postal Code

92868

Country

United States

Facility Name

Artemis Institute for Clinical Research

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

Facility Name

Amit Vijapura

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32256

Country

United States

Facility Name

Sarkis Clinical Trials

City

Lake City

State/Province

Florida

ZIP/Postal Code

32025

Country

United States

Facility Name

Meridien Research

City

Lakeland

State/Province

Florida

ZIP/Postal Code

33805

Country

United States

Facility Name

Innovative Clinical Research

City

Lauderhill

State/Province

Florida

ZIP/Postal Code

33319

Country

United States

Facility Name

Florida Clinical Research Center

City

Maitland

State/Province

Florida

ZIP/Postal Code

32751

Country

United States

Facility Name

Try Research

City

Maitland

State/Province

Florida

ZIP/Postal Code

32751

Country

United States

Facility Name

Scientific Clinical Research

City

North Miami

State/Province

Florida

ZIP/Postal Code

33161

Country

United States

Facility Name

Research Centers of America

City

Oakland Park

State/Province

Florida

ZIP/Postal Code

33334

Country

United States

Facility Name

Atlanta Institute of Medicine and Research

City

Alpharetta

State/Province

Georgia

ZIP/Postal Code

30005

Country

United States

Facility Name

Phoenix Medical Research

City

Prairie Village

State/Province

Kansas

ZIP/Postal Code

66206

Country

United States

Facility Name

Louisiana Research Associates

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70114

Country

United States

Facility Name

Louisiana Clinical Research

City

Shreveport

State/Province

Louisiana

ZIP/Postal Code

71101

Country

United States

Facility Name

Stanley Street Treatment and Resources

City

Fall River

State/Province

Massachusetts

ZIP/Postal Code

02720

Country

United States

Facility Name

Adams Clinical Trials

City

Watertown

State/Province

Massachusetts

ZIP/Postal Code

02472

Country

United States

Facility Name

Precise Research Centers, Inc.

City

Flowood

State/Province

Mississippi

ZIP/Postal Code

39232

Country

United States

Facility Name

St Louis Clinical Trials

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63141

Country

United States

Facility Name

Altea Research

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89102

Country

United States

Facility Name

Comprehensive Clinical Research

City

Berlin

State/Province

New Jersey

ZIP/Postal Code

08009

Country

United States

Facility Name

Center for Emotional Fitness

City

Cherry Hill

State/Province

New Jersey

ZIP/Postal Code

08002

Country

United States

Facility Name

The Medical Research Network, LLC

City

New York

State/Province

New York

ZIP/Postal Code

10128

Country

United States

Facility Name

Neuro-behavioral Clinical Research

City

Canton

State/Province

Ohio

ZIP/Postal Code

44718

Country

United States

Facility Name

Midwest Clinical Research Center

City

Dayton

State/Province

Ohio

ZIP/Postal Code

45417

Country

United States

Facility Name

Charak Clinical Research Center

City

Garfield Heights

State/Province

Ohio

ZIP/Postal Code

44125

Country

United States

Facility Name

Oklahoma Clinical Research Center

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73112

Country

United States

Facility Name

Pahl Pharmaceutical Professionals

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73112

Country

United States

Facility Name

CODA

City

Portland

State/Province

Oregon

ZIP/Postal Code

97214

Country

United States

Facility Name

Tipton Medical and Diagnostic Center aka Clinical Research Associates of Central PA

City

Altoona

State/Province

Pennsylvania

ZIP/Postal Code

16602

Country

United States

Facility Name

UPenn Treatment Research Center

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Carolina Clinical Trials

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29407

Country

United States

Facility Name

Pillar Clinical Research

City

Dallas

State/Province

Texas

ZIP/Postal Code

75243

Country

United States

Facility Name

InSite Clinical Research

City

DeSoto

State/Province

Texas

ZIP/Postal Code

75115

Country

United States

Facility Name

Aspen Clinical Research, LLC

City

Orem

State/Province

Utah

ZIP/Postal Code

84058

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35287034

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. Erratum In: Drug Alcohol Depend. 2022 Dec 1;241:109687.

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Safety and Tolerability Study of Depot Buprenorphine in Treatment Seeking Subjects With Opioid Use Disorder

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