A Multi-Site Open-Label Extension Study of MDMA-Assisted Psychotherapy for PTSD

NCT04714359 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: MAPPUSX
• Study Type: interventional
• Target: 87
• Locations: 3 countries
• Sites: 15

Brief Summary

The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective at reducing PTSD symptoms in people with PTSD who received placebo in a prior MDMA-assisted therapy study. The main question it aims to answer is: Do PTSD symptoms decrease in people who receive a flexible dose of MDMA (120 or 180 mg MDMA HCl) with therapy in three sessions? Participants will undergo three preparatory therapy sessions without any study drug, then three MDMA-assisted therapy sessions with a flexible dose of 80 or 120 mg, followed by three integrative therapy sessions without study drug after each MDMA-assisted therapy session.

Conditions

PTSD

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Visit 16 in PCL-5 Total Score

  The Post Traumatic Stress Disorder Checklist for DSM-5 (PCL-5) is a 20-item self-report questionnaire in which respondents indicate the presence and severity of PTSD symptoms, derived from the symptoms of PTSD per DSM-5. Participants indicate how much distress they have experienced in the last 2 weeks due to symptoms such as "Repeated, disturbing memories, thoughts, or images of a stressful experience from the past," "Trouble remembering important parts of a stressful experience from the past," and "Feeling irritable or having angry outbursts" on a five-point Likert-type scale (0=Not at all to 4=Extremely). The total severity score can range from 0 to 80 and lower scores indicate less PTSD symptoms.

  Baseline enrollment to approximately 18 weeks later (Visit 16 occurs 24 to 32 days after Experimental Session 3)

Secondary Outcomes (1)

• Change From Baseline to Visit 16 in Sheehan Disability Scale (SDS) Total Score

  Baseline enrollment to approximately 18 weeks later (Visit 16 occurs 24 to 32 days after Experimental Session 3)

Study Arms (1)

MDMA-assisted therapy

EXPERIMENTAL

Three open-label sessions of MDMA-assisted therapy, each scheduled approximately 1 month apart, with initial dose of midomafetamine HCl of 80 or 120 mg and optional supplemental dose half that of initial dose (40 or 60 mg) 1.5 to 2 hours later

Drug: Midomafetamine HCl

Interventions

Midomafetamine HCl DRUG

Initial doses per Experimental Session include 80 mg or 120 mg midomafetamine HCl, followed 1.5 to 2 hours later by a supplemental dose unless tolerability issues emerge. For an initial dose of 80 mg, a 40 mg supplemental dose will be used. For an initial dose of 120 mg, a 60 mg supplemental dose will be used. Total amounts of midomafetamine HCl to be administered per Experimental Session range from 80 mg to 180 mg.

Also known as: 3,4-methylenedioxymethamphetamine, MDMA HCl, midomafetamine, MDMA

MDMA-assisted therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Were previously enrolled in a parent study and (meet one of the following):
• At time of unblinding, their treatment assignment was to the placebo arm; or,
• Did not begin Experimental Sessions due to the COVID-19 global pandemic or other unforeseen circumstances;
• Completed fewer than three Experimental Sessions prior to Study Termination due to the COVID-19 global pandemic or other unforeseen circumstances.
• Are considered in good standing with the study site at which they enrolled in a parent study; if, in the opinion of the investigator, therapy team, and Medical Monitor, the participant was compliant with protocol requirements, even if they were unable to complete all study visits.
• 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
• Agree to the following lifestyle modifications: comply with requirements for fasting and refraining from certain medications prior to Experimental Sessions.
• 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.

You may not qualify if:

• 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 \[ms\] in males and \>460 ms in females corrected by Fridericia 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, such as myocardial infarction, cerebrovascular accident, or aneurysm
• Have symptomatic liver disease
• Have recent 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
• Have an active illicit or prescription drug substance use disorder within 12 months

Sponsors & Collaborators

• Lykos Therapeutics: lead

Study Sites (15)

New School Research

Los Angeles, California, 90004, United States

Location

San Francisco Insight and Integration Center

San Francisco, California, 94114, United States

Location

UCSF

San Francisco, California, 94122, United States

Location

Aguazul-Blue Water Inc.

Boulder, Colorado, 80302, United States

Location

Wholeness Center

Fort Collins, Colorado, 80525, United States

Location

Ray Worthy Psychiatry

New Orleans, Louisiana, 70123, United States

Location

Trauma Research Foundation

Boston, Massachusetts, 02446, United States

Location

NYU

New York, New York, 10016, United States

Location

New York Private Practice

New York, New York, 11012, United States

Location

Zen Therapeutic Solutions, LLC

Mt. Pleasant, South Carolina, 29464, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53705-2222, United States

Location

Numinus

Vancouver, British Columbia, V5R 5H3, Canada

Location

Numinus

Montreal, Quebec, H2W 1Y9, Canada

Location

Beer Yaakov Mental Health Center

Beer Yaaqov, Israel

Location

Tel Hashomer

Tel Aviv, Israel

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

N-Methyl-3,4-methylenedioxyamphetamine

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Lykos Therapeutics

trialdata@lykospbc.com

877-627-7722

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2021
• First Posted: January 19, 2021
• Study Start: March 8, 2021
• Primary Completion: November 1, 2023
• Study Completion: November 6, 2023
• Last Updated: June 6, 2025
• Results First Posted: November 29, 2024

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data and study-related documents will be available when the database has been locked and data has been unblinded.
• Access Criteria: Interested persons should correspond with the central contact for the multisite study.

Locations

IL (2); CA (2); US (11)