A Randomized, Double-Blind, Placebo-Controlled, Multi-Site Phase 3 Study of the Efficacy and Safety of Manualized MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder of Moderate or Greater Severity

MAPP2

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that can develop after a traumatic life experience that severely reduces quality of life. This multi-site, double-blind, placebo-controlled, randomized Phase 3 study will assess the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy compared to psychotherapy with placebo in participants diagnosed with at least moderate PTSD. The study will be conducted in up to N ≈ 100 participants. Participants will be randomized to receive a flexible dose of 80 or 120 mg MDMA or placebo, followed by a supplemental half-dose of 40 or 60 mg MDMA or placebo, unless contraindicated, with manualized psychotherapy in three monthly Experimental Sessions. This \~12-week Treatment Period will be preceded by three Preparatory Sessions with the participant and therapists. During the Treatment Period, each Experimental Session will be followed by three Integrative Sessions of non-drug psychotherapy.

2020-09-02

2022-10-30

2022-11-02

Completed

Early phase I

121

Inclusion Criteria: * Are at least 18 years old. * Are fluent in speaking and reading the predominantly used or recognized language of the study site. * Are able to swallow pills. * 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. * At baseline, have moderate PTSD diagnosis. 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.

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2024-01-24