Evaluation of the Efficacy of Sodium Oxybate in the Long-term Maintenance of Abstinence in Alcoholic Patients (GATE2)

Laboratorio Farmaceutico Ct S.r.l.

Status and phase: Completed; Phase 4

Conditions: Alcohol Use Disorder (AUD); Alcohol Dependence

Treatments: Drug: Sodium Oxybate; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04648423

GHBCR00/2

Details and patient eligibility

About

Additional pharmacotherapies in the treatment of alcohol dependence are needed. Sodium oxybate showed efficacy in the maintenance of abstinence in alcohol-dependent patients in several small randomized trials of short duration. The aim of the present phase III/IV study is to confirm in a randomized-controlled study the efficacy and safety of oral sodium oxybate in the maintenance of abstinence.

Full description

Alcohol dependence (AD) is the most severe form of alcohol use disorder. It occurs in 2.6% of people aged 15+ years worldwide and can result in a reduction of life-expectancy by several years as compared with the general population.

Currently, disulfiram, acamprosate and naltrexone are the main medicinal products registered for the maintenance of abstinence in AD patients. Although effective on the group level, effects sizes are limited, and many AD patients fail to respond to these medications. Therefore, additional pharmacological treatments are needed.

Sodium oxybate 50mg/kg/day showed evidence of efficacy compared to placebo and naltrexone in the maintenance of abstinence in AD patients in a series of open label and blinded randomized controlled trials (RCTs). However, studies were generally small and did not investigate the sustainability of the Sodium oxybate effect post-treatment.

The present phase III/IV RCT (GATE 2) aimed to confirm the efficacy and safety of oral Sodium oxybate in the maintenance of abstinence. Secondary aims included the assessment of sustained SMO effects during the 6-month medication free period immediately following the 6-month treatment period and monitoring the risk of Sodium oxybate dependence.

Enrollment: 314 patients

Sex: All

Ages: 21 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

The following subjects were recruited:

• males and females;
• of any ethnic group;
• age between 21 and 75 years at recruitment;
• documented alcohol dependency before weaning detected according to the CAGE instrument, classified according to the DSM-IV and ICD-10 and severity rated according to the MALT instrument;
• classified according to Lesch typology;
• having successfully undergone a detoxification program, encompassing a 10-day treatment period and a subsequent 10-day untreated follow-up;
• with a responsible relative or caregiver;
• having issued the informed consent.

Exclusion criteria

• subjects who did not quit alcohol drinking after the detoxification period;
• subjects with history of epilepsy or epileptics seizures not properly controlled by established anti-epileptic treatment;
• subjects with dependence from narcotics or other drugs of abuse;
• subjects without a stable address;
• subjects without a reference relative or caregiver;
• subjects with renai failure (blood creatinine >2.5 mg/dL and/or documented proteinuria >500 mg/day);
• subjects with heart failure or severe respiratory failure;
• subjects with hepatic encephalopathy stage lI-IV;
• subjects with severe psychiatric disorders requiring treatment with psychoactive medications (excluding short-term benzodiazepine treatments);
• subjects under treatment with clonidine, disulfiram (after the end of the detoxification period), haloperidol, bromocryptine, serotonine re-uptake inhibitors or other serotoninergic agents;
• female subjects who cannot assure not to become pregnant during the 7-month period covering treatment and the first treatment-free month of follow-up;
• documented pre-existent hypersensitivity to GHB;
• subjects unable or unwilling to issue the informed consent;
• participating to another clinica! investigation in the previous month prior to recruitment; 15. any other medicai condition which, according to the investigator, justifies the patient's exclusion from the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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314 participants in 2 patient groups, including a placebo group

sodium oxybate

Experimental group

Description:

Sodium oxybate solution for oral administration (175 mg/mL). Dose (body weight ≤ 65 kg): 19.0 mL daily, in 3 administrations, for 6 months Dose (body weight \> 65 kg): 22.5 mL daily, in 3 administrations, for 6 months

Treatment:

Drug: Sodium Oxybate

placebo

Placebo Comparator group

Description:

Placebo solution for oral administration. Dose (body weight ≤ 65 kg): 19.0 mL daily, in 3 administrations, for 6 months Dose (body weight \> 65 kg): 22.5 mL daily, in 3 administrations, for 6 months

Treatment:

Drug: Placebo