Extended-release Pharmacotherapy for Opioid Use Disorder

NCT05164549 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: 255522
• Study Type: interventional
• Target: 342
• Locations: 1 country
• Sites: 5

Brief Summary

The primary objective is a clinical superiority effectiveness contrast to standard of care. Reported following SPIRIT and CONSORT standards, the study will determine whether extended-release injectable depot Buprenorphine (XR-Bup) maintenance therapy for OUD over six months is clinically superior to standard-of-care, oral medication (sublingual Buprenorphine \[SL-Bup\] or oral methadone \[Met\]; together: Bup/Met)

Conditions

Opiate Substitution Treatment

Keywords

opiate; opioid; opioid treatment

Outcome Measures

Primary Outcomes (1)

• Count of days abstinent From illicit/non-medical opioids during weeks 2 to 24 (range: 0-161 days)

  Combining self-report information from Time-Line Follow-Back interview adapted from the Treatment Outcomes Profile and incorporating data from 12 scheduled urine drug screens.

  24 weeks

Secondary Outcomes (23)

• Clinical superiority of XR-Bup plus PSI versus Bup/Met plus PSI

  24 weeks

• Cost-effectiveness of XR-BUP versus Bup and Met

  24 weeks

• Safety of XR-Bup

  24 weeks

• Time (days) enrolled in study treatment (retention) to week 24

  24 weeks

• OUD remission status (DSM5 OUD severity; SCID-5-RV)

  24 weeks

Study Arms (4)

XR-Bup

EXPERIMENTAL

Extended-Release Buprenorphine, monthly, 300mg or 100mg

Drug: Buprenorphine Injectable Product

Bup/Met

ACTIVE COMPARATOR

Standard of Care; either Buprenorphine (including Subutex, Suboxone \& Espranor) or Methadone (Participant Preference).

Drug: Methadone; Drug: Buprenorphine

XR-Bup + PSI

EXPERIMENTAL

Extended-Release Buprenorphine, monthly, 300mg or 100mg + Personalised Psychosocial Intervention (PSI)

Drug: Buprenorphine Injectable Product

Bup/Met + PSI

ACTIVE COMPARATOR

Standard of Care; either Buprenorphine (including Subutex, Suboxone \& Espranor) or Methadone (Participant Preference) + Personalised Psychosocial Intervention (PSI)

Drug: Methadone; Drug: Buprenorphine

Interventions

Buprenorphine Injectable Product DRUG

Investigational Medicinal Product

Also known as: Sublocade®; prev. RBP-60000

XR-Bup; XR-Bup + PSI

Methadone DRUG

Standard of Care

Bup/Met; Bup/Met + PSI

Buprenorphine DRUG

Standard of Care

Also known as: Suboxone, Espranor, Subutex

Bup/Met; Bup/Met + PSI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 years (no upper age limit);
• Current diagnosis of DSM-5 OUD via SCID-5-RV (moderate-severe at baseline for current episode);
• Currently enrolled on Met (30mg/day or less) or sublingual Bup or Bup-NX (24mg/day or less) or Esp (18mg/day or less) and in the view of the clinician would be able to convert to XR-Bup within 7 days post randomisation;
• Voluntarily seeking treatment and able to attend the clinic as required in the protocol;
• Able to communicate in English to level required to accept standard care and psychosocial intervention;
• Possession of a contactable personal mobile phone or landline telephone number and ability to nominate at least one locator individual with a verifiable address and a telephone number to assist with the arrangement of follow-up appointments;
• Living circumstances judged to be of sufficient stability to be able to engage/adhere to the study protocol;
• Is not pregnant (confirmed) or breast feeding and, if currently or intending to have potentially procreative intercourse, agrees to use a birth control method (either oral hormonal contraceptives, barrier \[condom or diaphragm\], or Nexplanon implant) for the duration of the study.

You may not qualify if:

• Clinically significant medical condition or observed abnormalities on physical examination or laboratory investigation, including but not limited to:
• uncontrolled hypertension, significant heart disease (including angina and myocardial infarction in past 12 months), or any cardiovascular abnormality which is judged to be clinically significant;
• severe alcohol dependence/withdrawal syndrome which is judged to be clinically significant and may constitute a risk to the patient's safety;
• acute hepatitis taken as clinical jaundice on examination, or evidence of blood bilirubin level above the normal range for local reference criteria, or evidence of serum levels of aspartate aminotransferase, alanine aminotransferase levels that are more than three-times the upper limit of the normal range;
• History of allergic or adverse reactions to Bup or the proprietary ATRIGEL delivery system for XR-Bup (Sublocade®)\*;
• Clinically significant or uncontrolled mental health problems (including but not limited to psychosis, bipolar disorder, schizoaffective disorder), or history or evidence of organic brain disease or dementia that may compromise safety or compliance with the study protocol;
• Current (past 30 day) suicide plan or suicide attempt in past six months;
• Current criminal justice involvement with legal proceedings, which in the opinion of a medically qualified investigator indicates a risk that the patient would fail to complete the study protocol due to re-incarceration or move away from the centre's catchment area.
• Currently taking oral or depot naltrexone therapy or enrolment in any form of naltrexone therapy within 90 days prior to study screening;
• Any contraindication to Bup\*.
• Participant is ineligible if they have any allergic or adverse reactions or contraindication to Buprenorphine. If participant has any allergic or adverse reaction or contraindication to Met or naloxone, or excipients of Bup-NX or Esp they can be prescribed Bup within the trial.

Sponsors & Collaborators

• King's College London: lead
• South London and Maudsley NHS Foundation Trust: collaborator
• Greater Manchester Mental Health NHS Foundation Trust: collaborator
• Northumberland, Tyne and Wear NHS Foundation Trust: collaborator
• Birmingham and Solihull Mental Health NHS Foundation Trust: collaborator
• NHS Tayside: collaborator
• Bangor University: collaborator

Study Sites (5)

Birmingham and Solihull Mental Health NHS Foundation Trust

Birmingham, United Kingdom

Location

NHS Tayside

Dundee, United Kingdom

Location

South London and Maudsley NHS Foundation Trust

London, United Kingdom

Location

Greater Manchester Mental Health NHS Foundation Trust

Manchester, United Kingdom

Location

Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust

Newcastle upon Tyne, United Kingdom

Location

Related Publications (2)

• Marsden J, Kelleher M, Hoare Z, Hughes D, Bisla J, Cape A, Cowden F, Day E, Dewhurst J, Evans R, Hearn A, Kelly J, Lowry N, McCusker M, Murphy C, Murray R, Myton T, Quarshie S, Scott G, Turner S, Vanderwaal R, Wareham A, Gilvarry E, Mitcheson L. Extended-release pharmacotherapy for opioid use disorder (EXPO): protocol for an open-label randomised controlled trial of the effectiveness and cost-effectiveness of injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone. Trials. 2022 Aug 19;23(1):697. doi: 10.1186/s13063-022-06595-0.

  PMID: 35986418 BACKGROUND

• Marsden J, Kelleher M, Gilvarry E, Mitcheson L, Bisla J, Cape A, Cowden F, Day E, Dewhurst J, Evans R, Hardy W, Hearn A, Kelly J, Lowry N, McCusker M, Murphy C, Murray R, Myton T, Quarshie S, Vanderwaal R, Wareham A, Hughes D, Hoare Z. Superiority and cost-effectiveness of monthly extended-release buprenorphine versus daily standard of care medication: a pragmatic, parallel-group, open-label, multicentre, randomised, controlled, phase 3 trial. EClinicalMedicine. 2023 Nov 17;66:102311. doi: 10.1016/j.eclinm.2023.102311. eCollection 2023 Dec.

  PMID: 38045803 RESULT

Related Links

• EXPO Trial Primary Results Publication
• EXPO Trial Protocol

MeSH Terms

Interventions

Sublocade; Methadone; Buprenorphine; Buprenorphine, Naloxone Drug Combination

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Naloxone; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Mike Kelleher, Dr

  South London and Maudsley NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2021
• First Posted: December 20, 2021
• Study Start: August 6, 2019
• Primary Completion: April 29, 2022
• Study Completion: March 1, 2023
• Last Updated: January 19, 2024

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5)