Varenicline and Bupropion for Alcohol Use Disorder

NCT04167306 | Completed Phase 2 Results

• 2 other identifiers: COMB-BO82018-000048-24
• Study Type: interventional
• Target: 388
• Locations: 1 country
• Sites: 4

Brief Summary

The COMB study is a randomized double-blind placebo-controlled multicenter trial in Sweden on the efficacy of varenicline and bupropion, in combination and alone, for treatment of alcohol use disorder (AUD). Study design overview: A 13-weeks (91 days) multicenter clinical trial with four parallel groups. 95 subjects per treatment arm will be randomized into the study. 380 subjects with AUD will be randomized in total.

Conditions

Alcohol Use Disorder; Alcoholism; Alcohol Dependence

Outcome Measures

Primary Outcomes (2)

• Alcohol Consumption as Measured by Phosphatidylethanol (PEth) in Blood

  B-PEth: Objective marker for alcohol consumption measured in blood, measured at every study visit. Analysed as mean reduction of PEth per treatment arm, mITT.

  PEth is calculated as the mean value over the active steady state period (Day 21-Day77) compared to baseline (=screening visit value)

• Alcohol Consumption as Measured by Heavy Drinking Days (HDD)

  HDD is obtained by the time Line Follow Back procedure, defined as ≥70 grams for men and ≥56 grams for women according to FDA's guidelines. Analysed as mean reduction in HDD share per treatment arm, for mITT

  Number of HDD by 14 days is defined as a mean over the 8-week steady state active treatment period (Day 21-Day77) . ( D21-D77)/4 in order to get a 14 day-period measurment.

Secondary Outcomes (10)

• CDT

  CDT is calculated as the mean value over the active steady state period (Day 21-Day77) compared to baseline (=screening visit value)

• GGT

  GGT calculated as the mean value over the active steady state period (Day 21-Day77) compared to baseline (=screening visit value)

• Self-reported Alcohol Consumption Measured by Time-lime-follow-back

  CDT is calculated as the mean value over the active steady state period (Day 21-Day77) compared to baseline (=screening visit value)

• Alcohol Use Identification Test

  Mean difference between total score obtained at baseline and visit 1

• Self-reported Alcohol Craving

  Scale range: 0-100 mm. Minimum value: 0 = No craving. Maxumum value: 100 Maximum= Very strong craving. Craving is calculated as the mean value over the active steady state period (Day 21-Day77) compared to baseline (=screening visit value)

Study Arms (4)

1) Varenicline + Bupropion

EXPERIMENTAL

Investigational medicinal product (IMP) 1: Varenicline 0.5 mg and 1.0 mg and Investigational medicinal product (IMP) 2: Bupropion SR 150 mg

Drug: Varenicline Tartrate 1 mg b.i.d; Drug: Bupropion Hydrochloride 150 mg b.i.d

2) Varenicline + Placebo for Bupropion

EXPERIMENTAL

Investigational medicinal product (IMP) 1: Varenicline 0.5 mg and 1.0 mg and Placebo capsule for IMP 2 (bupropion)

Drug: Varenicline Tartrate 1 mg b.i.d; Other: Placebo for bupropion

3) Bupropion + Placebo for Varenicline

EXPERIMENTAL

Investigational medicinal product (IMP) 2: Bupropion SR 150 mg and Placebo capsule for IMP 1 (varenicline)

Drug: Bupropion Hydrochloride 150 mg b.i.d; Other: Placebo for varenicline

4) Placebo for Varenicline + Placebo for Bupropion

PLACEBO COMPARATOR

Placebo capsule for IMP 1 (varenicline) and Placebo capsule for IMP 2 (bupropion)

Other: Placebo for varenicline; Other: Placebo for bupropion

Interventions

Varenicline Tartrate 1 mg b.i.d DRUG

Capsules for oral use

Also known as: Champix

1) Varenicline + Bupropion; 2) Varenicline + Placebo for Bupropion

Bupropion Hydrochloride 150 mg b.i.d DRUG

Capsules for oral use

Also known as: Bupropion Sandoz

1) Varenicline + Bupropion; 3) Bupropion + Placebo for Varenicline

Placebo for varenicline OTHER

Capsules for oral use

3) Bupropion + Placebo for Varenicline; 4) Placebo for Varenicline + Placebo for Bupropion

Placebo for bupropion OTHER

Capsules for oral use

2) Varenicline + Placebo for Bupropion; 4) Placebo for Varenicline + Placebo for Bupropion

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Blood alcohol level below \<0.1‰ (0.1 g/L) at signing informed consent
• years of age at screening
• Moderate and severe AUD according to DSM-V (meeting ≥4 out of 11 criteria)
• B-PEth levels of ≥0.5 µmol/L at screening visit (visit 1)
• Continuous high alcohol consumption over the last 3 months prior to screening as defined by at least 2 HDD per week on a typical week
• Available phone number for contact
• Ability to speak and write in Swedish

You may not qualify if:

• Total abstinence between screening and randomization visit
• Treatment of alcohol withdrawal within 30 days of study initiation
• Pharmacological treatment within 3 months of study initiation and during the study period that may affect alcohol consumption, including but not exclusive to, varenicline, bupropion, disulfiram, acamprosate, naltrexone, nalmefene, baclofen, topiramate, ondansetron, mirtazapine, methylphenidate, dexamphetamine, atomoxetine, pregabalin, buprenorphine and methadone
• Non-pharmacological treatment within 3 months of study initiation and during the study period that may affect alcohol consumption
• Current continuous use of antidepressants, opioid analgesics, benzodiazepines, zopiclone, zolpidem, hydroxyzine, alimemazine, propiomazine, or other sedatives. (The sporadic use of these compounds is accepted.)
• Any concurrent medication that may affect the results of the trial or is considered to compromise the safety of the participants in the trial. (See SmPCs for possible interactions.)
• Laboratory hepatic values of \>3 times the upper limit of the normal range, creatinine clearance \<30 ml/min, or other clinically significant abnormalities in the screening laboratory values
• Blood pressure ≥180/110 at screening
• Pregnancy, breast-feeding and for premenopausal women, not using one of the contraceptive methods oral contraceptive, intrauterine contraceptive device (copper or hormonal) or subcutaneous inplant.
• Diabetes mellitus type 1 and diabetes mellitus type 2 in need of insulin treatment
• Any current psychiatric or somatic disorder or condition that may affect assessments or compromise participant's safety during the trial
• ASRS- v1.1, part A score ≥4 in the marked cut-off section
• MADRS score ≥ 20
• Current depression that is not mild (mild depression is accepted)
• Suicidality

Sponsors & Collaborators

• Vastra Gotaland Region: lead

Study Sites (4)

Beroendecentrum Malmö

Malmo, Region Skåne, Sweden

Location

Linköping University Hospital

Linköping, Region Östergötland, Sweden

Location

Stockholm Centre for Dependency Disorders,

Stockholm, Stockholms Läns Sjukvårdområde, Sweden

Location

Beroendekliniken, Sahlgrenska University Hospital, Västra Götalandsregionen

Gothenburg, Sweden

Location

Related Publications (2)

• Soderpalm B, Lido H, Franck J, Hakansson A, Lindqvist D, Heilig M, Guterstam J, Samuelson M, Askerup B, Wallmark-Nilsson C, de Bejczy A. Efficacy and safety of varenicline and bupropion, in combination and alone, for alcohol use disorder: a randomized, double-blind, placebo-controlled multicentre trial. Lancet Reg Health Eur. 2025 May 13;54:101310. doi: 10.1016/j.lanepe.2025.101310. eCollection 2025 Jul.

  PMID: 40487775 DERIVED

• de Bejczy A, Lido H, Soderpalm B. A randomized, double-blind, placebo-controlled, multicentre trial on the efficacy of varenicline and bupropion in combination and alone for treatment of alcohol use disorder: Protocol for the COMB study. PLoS One. 2024 Jan 11;19(1):e0296118. doi: 10.1371/journal.pone.0296118. eCollection 2024.

  PMID: 38206930 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Varenicline; Bupropion

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines; Propiophenones; Ketones; Organic Chemicals

Results Point of Contact

• Title: Andrea de Bejczy
• Organization: Addiction BIology Unit - Clinical Trials, Inst Neuroecience and Physiology, Gotheburg University/ Dep of Addictions and Dependency, Sahlgrenska University Hostpital

andrea.debejczy@neuro.gu.se

+46313424724

Study Officials

• Bo Söderpalm, Prof, MD

  Sahlgrenska University Hospital, Västra Götaland

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Appointed manufacturer produces, packs and labels the IMPs in two separate IMP kits and uses a blinding procedure accordance with internal standard operating procedure. IMP 1 and IMP 2, will have an unique Randomization Number generated randomly. For each randomization number, a sealed emergency code envelope will follow the shipment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2019
• First Posted: November 18, 2019
• Study Start: March 4, 2019
• Primary Completion: December 15, 2022
• Study Completion: December 15, 2022
• Last Updated: June 7, 2024
• Results First Posted: June 7, 2024

Record last verified: 2023-12

Locations

SE (4)