Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Therapy for Treatment of PTSD
Condition: PTSD
Intervention: Midomafetamine; Therapy
Intervention description: 80 to 120 mg MDMA; Non-directive therapy conducted during MDMA-assisted therapy session
Intervention MeSH terms: N-Methyl-3,4-methylenedioxyamphetamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Three sessions of MDMA-assisted therapy with flexible dose of MDMA (80 to 120 mg with optional supplemental half-dose)
Masking: None (Open Label)
Masking description: This study will be open label
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MDMA; methylenedioxymethamphetamine; therapy

Summary:

      This multi-site, open-label, Phase 2, lead-in study assesses the safety and effect of
      3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy in participants diagnosed with at
      least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified
      and trained to work on the sponsor's planned Phase 3 studies will treat at least one
      open-label participant in this study.

      This study will compare the effects of three open-label manualized Experimental Sessions of
      therapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80
      mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a supplemental
      half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session
      range from 80 mg to 180 mg. This ~12-week Treatment Period is preceded by three Preparatory
      Sessions. During the Treatment Period, each Experimental Session is followed by three
      Integrative Sessions of non-drug psychotherapy. The Primary Outcome measure is the change in
      Clinician Administered PTSD Scale for DSM 5 (CAPS-5) total severity scores from Baseline to
      Primary Endpoint (Visit 19).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Are at least 18 years old

          -  Are fluent in speaking and reading the predominantly used or recognized language of
             the study site

          -  Agree to have study visits recorded, including Experimental Sessions, Independent
             Rater assessments, and non-drug psychotherapy sessions

          -  Must provide a contact (relative, spouse, close friend or other caregiver) who is
             willing and able to be reached by the investigators in the event of a participant
             becoming suicidal or unreachable.

        Must agree to inform the investigators within 48 hours of any medical conditions and
        procedures

          -  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 10 days after the last Experimental Session.

          -  Must not participate in any other interventional clinical trials during the duration
             of the study,

          -  Must be willing to remain overnight at the study site after each Experimental Session
             and be driven home after, and commit to medication dosing, therapy, and study
             procedures

          -  Meet DSM-5 Criteria for Severe PTSD

        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