Food Effects on Bioavailability of MDMA in Healthy Volunteers
Condition: Pharmacokinetics
Study type: Interventional
Phase: Phase 1

Summary: 
      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: 
      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.
    

Intervention name(s): MDMA
Intervention type(s): Drug
Intervention description(s): 100 mg MDMA (equivalent to 120 mg MDMA HCl)
Other intervention name(s): 3,4-methylenedioxymethamphetamine; midomafetamine
Intervention MeSH terms: N-Methyl-3,4-methylenedioxyamphetamine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention 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)
Primary purpose: Basic Science
Keywords: MDMA; Metabolism; Methylenedioxymethamphetamine