MDMA in Subjects With Moderate Hepatic Impairment and Subjects With Normal Hepatic Function

Summary

Participation Requirements

Description

PTSD is a serious debilitating disorder that negatively impacts a person's daily life. 3,4-methylenedioxymethamphetamine (MDMA) is a ring-substituted phenylisopropylamine derivative that releases serotonin, norepinephrine and dopamine. MDMA has been shown to reduce defenses and fear of emotional inj...

PTSD is a serious debilitating disorder that negatively impacts a person's daily life. 3,4-methylenedioxymethamphetamine (MDMA) is a ring-substituted phenylisopropylamine derivative that releases serotonin, norepinephrine and dopamine. MDMA has been shown to reduce defenses and fear of emotional injury, enhance communication, and increase empathy, creating productive psychological state that enhances the therapeutic process for the treatment of PTSD and other anxiety disorders. This is supported by data from an international series of Phase 2 pilot studies of MDMA-assisted psychotherapy conducted by the sponsor that provide preliminary evidence that chronic PTSD, independent of cause, is treatable with two to three sessions of MDMA-assisted psychotherapy and associated non-drug preparatory and integrative psychotherapy. The results from multiple independent studies in Phase 2 efficacy analyses demonstrate superiority of MDMA-assisted psychotherapy over psychotherapy with placebo and low dose MDMA. This protocol is for a Phase 1, open-label study with a primary purpose of evaluating the effect of moderate hepatic impairment in the pharmacokinetics of MDMA and its active metabolite, 3,4-methylene-dioxyamphetamine (MDA), and determining whether an adjustment to the dosage would be indicated in this group of patients in comparison to patients with normal liver function. Because people with moderate hepatic impairment may experience greater exposure to drug than people without it, the secondary purpose of this study is to evaluate the effect of moderate hepatic impairment on the safety and tolerability of oral MDMA, with special attention to ECG data. The study will enroll eight participants, ages 18 to 65 years old, with moderate hepatic impairment, and eight healthy controls with normal hepatic function who are matched with participants with moderate impaired hepatic function on the basis of age, weight and gender. Participants who give their written informed consent will be screened for study participation that will include a physical examination, assessing current and prior medical and physical health, and a baseline electrocardiogram (ECG) reading. If applicable, they may begin tapering off any contraindicated psychiatric medication. Participants who meet study criteria will receive a single dose of 80 mg MDMA on the first day of a three-day stay at the study site. Blood will be collected periodically in order to calculate pharmacokinetics of MDMA and its active metabolite methylenedioxyamphetamine (MDA). Blood will be collected ten times on Day 1 (-5 min, 0 hours (drug administration), 0.5 h, 1, 2, 4, 6, 7, 10 and 12 hours), starting five minutes before drug administration. Subjective effects of MDMA will be assessed through 15 visual analog scales at similar time points to blood collection, at 0.5, 1, 2, 4, 6 and 7 hours post-drug. There will be six 12-lead ECG measurements on Day 1. Participants will remain at the study site for two more days. Drug safety will be assessed by measuring blood pressure, heart rate and body temperature after MDMA administrations, collecting adverse events throughout the study and measuring suicidal thoughts or behaviors with the Columbia Suicide Severity Rating Scale (C-SSRS). Blood will be collected 24 and 36 hours after drug administration, and ECG will be performed on Day 2, and a single ECG and blood draw will occur on Day 3, 4 and 5. Participants will return for eight and 15 days after drug administration. They will have a single blood draw on each day. The study ends 15 days after drug administration, approximately one month after screening. The primary outcome measure will be area under the curve from dosing to last dose (AUC) of MDMA and MDA. AUC will be computed from plasma collected multiple times after a single dose of MDMA, twice on the day following the day of drug administration, and once daily for three more days. Other pharmacokinetic measures will be maximal values of MDMA and MDA (Cmax), and time to reach maximum MDMA and MDA levels (Tmax). Safety measures will also include a comparison of subjective effects across groups, ECG readings, number of adverse events, and suicidal ideation or behavior as measured via C-SSRS during the study.

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