Clinical Trial to Evaluate Pharmacological Interactions Between γ-hydroxybutyrate (GHB) and Cobicistat

NCT04322214 | Completed Phase 1

• 2 other identifiers: GHB_Cobi2019-002122-71
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Gamma-hydroxybutyric acid (GHB) is a popular "party drug" because it is inexpensive and easy to ingest. The calming and euphoric effects of GHB in low doses have given the drug the nickname "liquid ecstasy". However, at doses \>60 mg/kg coma, convulsions, and respiratory depression can occur. If the drug combinates with alcohol these effects intensify, especially respiratory depression and hypotension. Lately a phenomenon called Chemsex has been spreading across big European cities. This is a form of recreational drug use and it is believed that can be, in part, the cause of the increasing in consumption of GHB. Chemsex is especially common among men who have sex with other men (MSM) and in people living with HIV, with up to 50% of HIV-positive MSM reporting to be engaged in chemsex in recent months. This population is specially concerning since the combination of ART with the drug can cause pharmacological interactions leading to overdose. Specifically, this study intends to evaluate the drug interaction with low doses of cobicistat, an antiretroviral drug enhancer, since there are two case reports of life-threatening overdoses in patients on treatment with high doses of another enhancer that has a similar effect than cobicistat, but there are no studies about interactions with low doses.

Conditions

Pharmacokinetic Interactions; HIV

Keywords

pharmacokinetic interactions; chemsex; GHB; cobicistat; γ-hydroxybutyrate

Outcome Measures

Primary Outcomes (2)

• concentration in plasma of GHB

  mg/dl

  days 5 and 17

• Proportion of participants reporting adverse events.

  % of participants developing related adverse events.

  Since baseline to day 28

Secondary Outcomes (5)

• physiological effects: blood pressure

  days 5 and 17

• physiological effects: heart rate

  days 5 and 17

• physiological effects : oxygen saturation

  days 5 and 17

• subjective effects of GHB -ARCI

  days 5 and 17

• subjective effects of GHB - Visual analog scale

  days 5 and 17

Study Arms (2)

COBI period (5 days) + Placebo period (5 days)

EXPERIMENTAL

volunteers will receive once daily cobicistat for 5 days. On day 5, participants will receive a single oral dose of GHB. After a washout period for 7 days, volunteers will receive once-daily placebo for 5 days. On day 5, participants will receive a single oral dose of GHB

Drug: Cobicistat 150 MG; Drug: Placebo; Drug: GHB

Placebo period (5 days) + COBI period (5 days)

EXPERIMENTAL

volunteers will receive once-daily placebo for 5 days. On day 5, participants will receive a single oral dose of GHB. After a washout period for 7 days, volunteers will receive once daily cobicistat for 5 days. On day 5, participants will receive a single oral dose of GHB.

Drug: Cobicistat 150 MG; Drug: Placebo; Drug: GHB

Interventions

Cobicistat 150 MG DRUG

once daily cobicistat (150 mg QD) for 5 days

Also known as: Cobicistat

COBI period (5 days) + Placebo period (5 days); Placebo period (5 days) + COBI period (5 days)

Placebo DRUG

once daily lactose capsules (as aspect cobicistat capsules)

COBI period (5 days) + Placebo period (5 days); Placebo period (5 days) + COBI period (5 days)

GHB DRUG

single oral dose of GHB (25 mg/kg) on days 5 and 17

Also known as: XYREM

COBI period (5 days) + Placebo period (5 days); Placebo period (5 days) + COBI period (5 days)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females\* aging 18-45 years.
• Body weight ranging between 50 and 100 Kg.
• Previous experience with the consumption of sedatives (alcohol, cannabis, benzodiazepines, GHB or other hypnotics).
• Absence of abnormalities in the screening ECG and blood/urine tests.
• Agree with the study procedures and signature of the informed consent.
• Women of childbearing potential must have a negative pregnancy test prior to randomization into the study and commitment to use at least one of these birth control methods: male or female condom with or without spermicide, cap, diaphragm or sponge with or without spermicide, intrauterine device, bilateral tubal occlusion, vasectomized partner, sexual abstinence during the study. Condom use is considered as an additional method of contraception only and cannot be the only method of contraception used as not been considered an effective method by the Clinical Trial Facilitation Group (CTFG) guidelines.
• Based on ICH, M3 (R2) 2009 a woman is considered of childbearing potential: fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include tubal ligation, hysterectomy, bilateral oophorectomy.

You may not qualify if:

• Prior history of medical or psychiatric adverse reaction following GHB consumption.
• Current substance use disorder (DSM-V, dependence, addiction) of any drug or substance of abuse.
• Prior history of substance use disorder (DSM-V, drug use disorder or addiction) of any drug or substance of abuse (except nicotine).
• Smokers\>10 cigarettes/day.
• History of any physical condition or major surgery within the previous three months.
• History of individual psychiatric conditions or schizophrenia in first-degree relatives.
• History of gastrointestinal, hepatic, renal diseases or other conditions which, in opinion of the investigator, may affect drug absorption, distribution, metabolism or elimination.
• Alcohol intake higher than 4 units/day (40 g) in men or 2 units/day (20 g) in women.
• Positive urine drug test (Amphetamines, Barbiturates, Benzodiazepines, Cocaine, MDMA, Methamphetamine, Morphine/Opioids, Methadone, tricyclic antidepressants, THC)
• HIV infection, chronic hepatitis C (IgG VHC) or B (HBsAg).
• Lactose intolerance
• Pregnancy, lactation, or planned pregnancy during the study period.
• Current or recent pharmacological treatment (≥3 doses per week) in the last 2 weeks
• Blood donation in the 3 previous months
• Participation in another clinical trial in the previous 3 months

Sponsors & Collaborators

• Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia: lead

Study Sites (1)

José

Badalona, Barcelona, 08916, Spain

Location

Related Publications (1)

• Molto J, Bailon L, Perez-Mana C, Papaseit E, Miranda C, Martin S, Mothe B, Farre M. Absence of drug-drug interactions between gamma-hydroxybutyric acid (GHB) and cobicistat. J Antimicrob Chemother. 2021 Dec 24;77(1):181-184. doi: 10.1093/jac/dkab359.

  PMID: 34561695 DERIVED

MeSH Terms

Conditions

Chemsex

Interventions

Cobicistat; Sodium Oxybate

Condition Hierarchy (Ancestors)

Sexual Behavior; Behavior

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydroxybutyrates; Butyrates; Hydroxy Acids

Study Officials

• José Moltó

  Germans Trias i Pujol Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will undergo two 5-day treatment periods (COBI and placebo) separated by a 7-day washout period: * COBI period: volunteers will receive once daily cobicistat (150 mg QD) for 5 days. * Placebo period: volunteers will receive once-daily placebo (lactose) for 5 days. On day 5 of each treatment period, participants will receive a single oral dose of GHB (25 mg/kg).

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: March 26, 2020
• Study Start: January 30, 2020
• Primary Completion: March 30, 2020
• Study Completion: April 30, 2020
• Last Updated: July 22, 2020

Record last verified: 2020-07

Locations

ES (1)