Food Effects on Bioavailability of MDMA in Healthy Volunteers

Study Overview
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Brief Summary
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This protocol is a Phase 1 open-label study with a primary purpose of evaluating the food effect of a high calorie meal as compared to fasting conditions on the relative bioavailability of oral MDMA capsules in healthy volunteers. In addition, increases in heart rate are anticipated following MDMA administration. Therefore, the secondary purpose of this study is to evaluate the effect of food on the safety and tolerability of oral MDMA, as well as MDMA effects on electrocardiogram (ECG). Directly comparing the pharmacokinetics of MDMA and its active metabolite MDA, in a within-subject crossover study will allow for assessment of any impacts of food and inform product labeling.

Detailed Description
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The sponsor has completed a Phase 3 study of MDMA-assisted therapy for individuals diagnosed with severe PTSD demonstrating the safety and efficacy of this treatment. However, the effect of food intake on the absorption and bioavailability of orally administered MDMA is not yet well characterized. This phase I, open-label, randomized sequence, multi-dose, 2-period crossover pharmacokinetic (PK) study assesses the effect of food on the relative bioavailability of MDMA. In addition, an increase in heart rate is anticipated following MDMA administration. Therefore, the secondary purpose of this study is to evaluate the effect of food on the safety and tolerability of oral MDMA, as well as MDMA effects on ECG. Potential participants will be identified by the clinical site and invited to phone screen for the study. Following informed consent, potential study participants will undergo screening examinations to assess eligibility for inclusion in the study. Participants will be randomized to receive one of two conditions before the other: Fasted Treatments: 10 hours of fasting followed by MDMA administration with 240 mL water. Fed Treatments: A high-fat (approximately 50 percent of total caloric content of the meal) and high-calorie (approximately 800 to 1000 calories) meal will be consumed within 30 minutes of MDMA administration. Participants will be confined at the Clinical Research Unit (CRU) for each Dosing Session from the time of check-in on the night before dosing until discharge 48 hours after dosing. MDMA will be administered on Day 1 following the treatment sequence to which the participant has been randomized. Concentration-time profiles of MDMA will be determined in the time interval 0-72 hours post-dose, according to the expected PK profiles of MDMA and its metabolites. Participants will remain at the CRU for at least 36 hours after administration of study drug for collection of serial blood samples for PK analysis and safety monitoring. An additional outpatient visit will occur 72 hours after dosing to collect a final PK sample and perform safety assessments.

Official Title
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A Phase 1, Single Center, Open Label, Randomized Sequence, 2-period Cross-over Study to Determine the Effect of Food on the Relative Bioavailability of 3,4-methylenedioxymethamphetamine (MDMA) Oral Formulation in Healthy Volunteers

Conditions
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Pharmacokinetics

Intervention / Treatment
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* Drug: MDMA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are fluent in speaking and reading the predominantly used or recognized language of the study site. Are able to swallow pills. If of childbearing potential, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 7 days after the last Experimental Session. Exclusion Criteria: Are not able to give adequate informed consent. Have uncontrolled hypertension. Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds [ms] corrected by Bazett's formula). Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome). Have evidence or history of significant medical disorders. Have symptomatic liver disease. Have history of hyponatremia or hyperthermia. Weigh less than 48 kilograms (kg). Are pregnant or nursing, or are of childbearing potential and are not practicing an effective means of birth control. Are abusing illegal drugs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants who are enrolled in the study will be randomized to 1 of 2 dosing regimens, both of which receive the same intervention in opposite order. Group 1 receives a Fasted Treatment followed by a Fed Treatment, while Group 2 receives a Fed Treatment followed by a Fasted Treatment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fasted Treatments with 100 mg of MDMA<br>Following an overnight fast of at least 10 hours, participants will be administered 100 mg MDMA (equivalent to 120 mg MDMA HCl) with 240 mL of water. No food should be allowed for at least 4 hours post-dose. | Drug: MDMA<br>* 100 mg MDMA (equivalent to 120 mg MDMA HCl)<br>* Other names: 3,4-methylenedioxymethamphetamine;|
| Active Comparator: Fed Treatments with 100 mg of MDMA<br>A high-fat (approximately 50 percent of total caloric content of the meal) and high-calorie (approximately 800 to 1000 calories) meal will be used as a test meal for food-effect evaluation. Following an overnight fast of at least 10 hours, participants will start the recommended meal 30 minutes prior to administration of the drug product. Participants will eat this entire meal in 30 minutes or less. 100 mg MDMA (equivalent to 120 mg MDMA HCl) will be administered 30 minutes after start of the meal with 240 mL of water. | Drug: MDMA<br>* 100 mg MDMA (equivalent to 120 mg MDMA HCl)<br>* Other names: 3,4-methylenedioxymethamphetamine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve from dosing time to last measurement - Plasma concentration of MDMA | Computed exposure to MDMA using blood collected periodically at pre-dose as well as 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 12 hours post drug administration. | 0 to 1 day after drug administration | 
| Area under the curve from dosing time to last measurement - Plasma concentration of active metabolite MDA | Computed exposure to MDMA using blood collected periodically at pre-dose as well as 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 12 hours post drug administration | 0 to 1 day after drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDMA, Metabolism, Methylenedioxymethamphetamine