Starting Treatment With Agonist Replacement Therapies (START)

NCT00315341 | Completed Phase 4 Results DMC

• 2 other identifiers: NIDA-CTN-0027U10DA013045
• Study Type: interventional
• Target: 1,269
• Locations: 1 country
• Sites: 9

Brief Summary

The Food and Drug Administration (FDA) has requested a study comparing buprenorphine/naloxone (BUP/NX) and methadone (MET) on indices of hepatic safety.

Conditions

Opiate-related Disorders

Outcome Measures

Primary Outcomes (1)

• Hepatic Safety

  Participants were categorized according liver transaminase (ALT, AST) levels in blood comparing the baseline sample to any and all subsequent samples in the following manner: A: both ALT and AST started at less than or equal to two times the ULN and remained at two times or less ULN throughout the study B: either ALT or AST started at less than or equal to 2 x ULN and at any point in study exceeded 2 x ULN C: Either ALT or AST started \> 2 x ULN, decreased (both ALT and AST) to \< 2 x ULN, and remained \< 2 x ULN D: Either ALT or AST started \> 2 x ULN and remained above 2 x ULN throughout the study

  24 Weeks

Study Arms (2)

Buprenorphine/Nx

EXPERIMENTAL

For the BUP/NX group, all participants will receive up to 16 mg BUP/4 mg NX on day 1 and up to 32 mg BUP/8 mg NX on day 2. It is recommended that dose changes be made in 2 to 8 mg buprenorphine increments, with the range of allowable daily doses between 2 mg and 32 mg starting on day 3 and thereafter according to clinical impression and depending upon the participant's clinical need. Investigators are encouraged to dose adequately to decrease craving and to obtain negative urine toxicology specimens.

Drug: Buprenorphine/naloxone

Methadone

ACTIVE COMPARATOR

For the MET group, all participants will receive a maximum of 30 mg for the first dose and a maximum of 40 mg on Day 1. It is recommended that participants receive a dose on day 2 that is 10 mg higher than their total day 1 dose, and a dose on day 3 that is 10 mg higher than their total day 2 dose, unless, in the clinical judgment of the physician, a slower induction is needed. Doses will be adjusted on Day 4 and thereafter according to clinical impression and depending upon the participant's clinical need with no specific upper limit. Investigators are encouraged to dose adequately to decrease craving and to obtain negative urine toxicology specimens.

Drug: Methadone

Interventions

Buprenorphine/naloxone DRUG

Participants receive up to 16 mg BUP/4 mg NX on day 1 and up to 32 mg BUP/8 mg NX on day 2. It is recommended that dose changes be made in 2 to 8 mg increments, with the range of allowable daily doses between 2 mg and 32 mg starting on day 3 and thereafter according to clinical impression and depending upon the participant's clinical need.

Buprenorphine/Nx

Methadone DRUG

Participants will receive a maximum of 30 mg for the first dose and a maximum of 40 mg on Day 1. It is recommended that participants receive a dose on day 2 that is 10 mg higher than their total day 1 dose, and a dose on day 3 that is 10 mg higher than their total day 2 dose, unless, in the clinical judgment of the physician, a slower induction is needed. Doses will be adjusted on Day 4 and thereafter according to clinical impression and depending upon the participant's clinical need with no specific upper limit.

Methadone

Eligibility Criteria

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

You may qualify if:

• Were age 18 years or older,
• Met DSM-IV-TR criteria for opioid dependence,
• Were in good general health, or, in case of a medical/psychiatric condition requiring ongoing treatment, were under the care of a physician willing to continue participant's medical management and cooperate with study physicians,
• For female participants, use of one of the following acceptable methods of birth control:
• oral contraceptives
• barrier (diaphragm or condom) with spermicide
• IUD
• intrauterine progesterone contraceptive system
• levonorgestrel implant
• medroxyprogesterone acetate contraceptive injection
• contraceptive transdermal patch
• hormonal vaginal contraceptive ring
• surgical sterilization
• complete abstinence from sexual intercourse
• Able to read and verbalize understanding of the study and voluntarily sign study informed consent form.

You may not qualify if:

• ALT or AST values \> 5 times the upper limit of normal as per testing laboratory range criteria,
• ALP values \>3 times the upper limit of normal per testing laboratory criteria,
• Any documented past or present history of ascites, presence of esophageal or gastric varices, hepatic encephalopathy or other signs of significant liver disease as indicated by a Model for Endstage Liver Disease score (Kamath et al., 2001) of ≥11,
• Total bilirubin \> 2.0 mg/dl (participants with documented Gilbert's syndrome were not excluded based on this criterion),
• Prothrombin time more than 3 seconds prolonged,
• Albumin level less than 2.5 g/dl,
• Any cardiopathy or risk factor listed below without evidence of a normal ECG\* with report performed within 6 months prior to first study medication dose,
• Congestive heart failure
• Left ventricular hypertrophy
• Bradycardia
• Hereditary QT prolongation
• Uncorrected electrolyte imbalance
• Concomitant medications that are known to have a risk of QT interval prolongation; refer to Appendix D for a list of medications.
• Note: The list was not all-inclusive.
• \*An ECG was abnormal if one or more of the following occurred:

Sponsors & Collaborators

• University of California, Los Angeles: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (9)

Matrix Institute

Los Angeles, California, 90016, United States

Location

Bi-Valley Medical Clinic INC.

Sacramento, California, 95816, United States

Location

BAART; Turk Street Clinic

San Francisco, California, 94102, United States

Location

Hartford Dispensary

Hartford, Connecticut, 06120, United States

Location

CT Counseling Centers

Waterbury, Connecticut, 06705, United States

Location

Addiction Research & Treatment Corp

Brooklyn, New York, 11201, United States

Location

CODA-Research

Portland, Oregon, 97214, United States

Location

NET Steps

Philadelphia, Pennsylvania, 19137, United States

Location

Evergreen Treatment Services

Seattle, Washington, 98134, United States

Location

Related Publications (8)

• Saxon AJ, Ling W, Hillhouse M, Thomas C, Hasson A, Ang A, Doraimani G, Tasissa G, Lokhnygina Y, Leimberger J, Bruce RD, McCarthy J, Wiest K, McLaughlin P, Bilangi R, Cohen A, Woody G, Jacobs P. Buprenorphine/Naloxone and methadone effects on laboratory indices of liver health: a randomized trial. Drug Alcohol Depend. 2013 Feb 1;128(1-2):71-6. doi: 10.1016/j.drugalcdep.2012.08.002. Epub 2012 Aug 22.

  PMID: 22921476 RESULT

• Brandt L, Odom GJ, Hu MC, Castro C, Balise RR; CTN-0094 Team. Empirically contrasting urine drug screening-based opioid use disorder treatment outcome definitions. Addiction. 2024 Jul;119(7):1289-1300. doi: 10.1111/add.16494. Epub 2024 Apr 14.

  PMID: 38616571 DERIVED

• Wang K, Shafique S, Xiao D, Walter SM, Liu Y, Piamjariyakul U, Xie C. Repeated measures analysis of opioid use disorder treatment on clinical opiate withdrawal scale in a randomized clinical trial: sex differences. J Addict Dis. 2024 Jan-Mar;42(1):33-44. doi: 10.1080/10550887.2022.2131957. Epub 2023 Jan 19.

  PMID: 36655851 DERIVED

• Nielsen S, Tse WC, Larance B. Opioid agonist treatment for people who are dependent on pharmaceutical opioids. Cochrane Database Syst Rev. 2022 Sep 5;9(9):CD011117. doi: 10.1002/14651858.CD011117.pub3.

  PMID: 36063082 DERIVED

• Nwabueze C, Elom H, Liu S, Walter SM, Sha Z, Acevedo P, Liu Y, Su BB, Xu C, Piamjariyakul U, Wang K. Gender differences in the associations of multiple psychiatric and chronic conditions with major depressive disorder among patients with opioid use disorder. J Addict Dis. 2022 Apr-Jun;40(2):168-178. doi: 10.1080/10550887.2021.1957639. Epub 2021 Jul 30.

  PMID: 34328394 DERIVED

• Crist RC, Li J, Doyle GA, Gilbert A, Dechairo BM, Berrettini WH. Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate. Am J Drug Alcohol Abuse. 2018;44(4):431-440. doi: 10.1080/00952990.2017.1420795. Epub 2018 Jan 15.

  PMID: 29333880 DERIVED

• Woody GE, Bruce D, Korthuis PT, Chhatre S, Poole S, Hillhouse M, Jacobs P, Sorensen J, Saxon AJ, Metzger D, Ling W. HIV risk reduction with buprenorphine-naloxone or methadone: findings from a randomized trial. J Acquir Immune Defic Syndr. 2014 Jul 1;66(3):288-93. doi: 10.1097/QAI.0000000000000165.

  PMID: 24751432 DERIVED

• Hser YI, Saxon AJ, Huang D, Hasson A, Thomas C, Hillhouse M, Jacobs P, Teruya C, McLaughlin P, Wiest K, Cohen A, Ling W. Treatment retention among patients randomized to buprenorphine/naloxone compared to methadone in a multi-site trial. Addiction. 2014 Jan;109(1):79-87. doi: 10.1111/add.12333. Epub 2013 Oct 9.

  PMID: 23961726 DERIVED

MeSH Terms

Interventions

Buprenorphine, Naloxone Drug Combination; Methadone

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Walter Ling, M.D.
• Organization: University of California, Los Angeles

lwalter@ucla.edu

(310) 933-8111

Study Officials

• Walter Ling, M.D.

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Andrew Saxon, M.D.

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 16, 2006
• First Posted: April 18, 2006
• Study Start: April 1, 2006
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: January 6, 2017
• Results First Posted: January 6, 2017

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)