NCT03769064

Study for Naltrexone on the Abuse Potential of Methylphenidate

Phase 1, Single-dose, Double-blind, Rand., Placebo- and Active-controlled, 4-period, 4-sequence Crossover, Proof-of-Concept Study to Evaluate Effect of Naltrexone on Abuse Potential of Methylphenidate in Healthy Recreational Stimulant Users

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 94 (actual)
• Sponsor: Avekshan LLC · Industry
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

The current abuse liability study aims to assess the potential for co-administration of naltrexone (NTX) to reduce the abuse potential of methylphenidate (MPH).

Detailed description

The abuse of MPH, as a Schedule II substance, is a well-documented problem. Studies in animal models, including primates, show that high-dose MPH can produce reinforcement or reward. A number of studies suggest that the rapid elevation of MPH levels in the blood and brain that occurs following intranasal or oral administration of supra-therapeutic doses is a key requirement for development of MPH-associated euphoria, reinforcement, and addiction. The concerns about MPH abuse potential and addiction often play a role in the decision of patients, parents, or physicians who opt against treatment with MPH, despite its effectiveness. This provides an imperative for development of MPH formulations that are therapeutically potent but with lower abuse potential. Methylphenidate acts mainly through the dopaminergic system. At sufficiently high doses, MPH can also activate the mu opioid receptors (MOPR) in the brain. Recent data indicate that blockade of MOPRs by naltrexone (NTX) blocks the rewarding effects of MPH in mice. Clinical studies on the modulatory effect of NTX on dopamine release following chronic amphetamine use also support the involvement of opioid-dopamine interactions in the reinforcing and rewarding effects of amphetamine. These data support the hypothesis that NTX will block the reinforcing effect of MPH in humans.

Conditions

• Naltrexone
• Methylphenidate Abuse

Interventions

Type	Name	Description
DRUG	Placebo	Potential subjects will be screened to determine their eligibility for the study within 28 days of the first dose in the Qualification Phase (i.e., Days -28 to -2). Eligible subjects will be admitted to the clinical site on Day -1 of the Qualification Phase (Part 1) and randomized on Day 1 to receive placebo and MPH (60 mg) in 1 of 2 sequences with a 48-hour washout between dose administrations (i.e., dose administration on Days 1 and 3).
DRUG	Methylphenidate 60 mg	Potential subjects will be screened to determine their eligibility for the study within 28 days of the first dose in the Qualification Phase (i.e., Days -28 to -2). Eligible subjects will be admitted to the clinical site on Day -1 of the Qualification Phase (Part 1) and randomized on Day 1 to receive placebo and MPH (60 mg) in 1 of 2 sequences with a 48-hour washout between dose administrations (i.e., dose administration on Days 1 and 3).
DRUG	Treatment Phase Sequence 4213	Subjects will be administered single doses on Days 1, 4, 7, and 10 of the Treatment Phase.
DRUG	Treatment Phase Sequence 2134	Subjects will be administered single doses on Days 1, 4, 7, and 10 of the Treatment Phase.
DRUG	Treatment Phase Sequence 1342	Subjects will be administered single doses on Days 1, 4, 7, and 10 of the Treatment Phase.
DRUG	Treatment Phase Sequence 3421	Subjects will be administered single doses on Days 1, 4, 7, and 10 of the Treatment Phase.

Timeline

• Start date: 2018-03-27
• Primary completion: 2018-06-20
• Completion: 2018-06-20
• First posted: 2018-12-07
• Last updated: 2018-12-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study