Trial Outcomes & Findings for Open Label Study of MDMA-assisted Psychotherapy for Treatment of PTSD With Optional fMRI Sub-Study (NCT NCT04030169)

Last Updated: 2025-01-28

Results Overview

The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a 30-item semi-structured interview assessing PTSD in the past month through diagnostic and symptom severity scores anchored to a DSM-5 defined traumatic event. The CAPS-5 produces a Total Severity Score based on severity of PTSD domains described in the DSM-5, as well as a categorical rating indicating whether a participant meets PTSD diagnostic criteria. CAPS-5 Total Symptom Severity scores range from 0 to 80 with higher values designating greater symptom severity. CAPS-5 assigns PTSD diagnosis as being present or absent.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

13 weeks post-baseline

Results posted on

2025-01-28

Participant Flow

Participant milestones

Participant milestones
Measure	MDMA-assisted Psychotherapy Open-label administration of 80 to 120 mg midomafetamine HCl in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg offered 1.5 to 2 hrs after the initial dose, respectively.
Overall Study STARTED	21
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Open Label Study of MDMA-assisted Psychotherapy for Treatment of PTSD With Optional fMRI Sub-Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MDMA-assisted Psychotherapy n=21 Participants Open-label administration of 80 to 120 mg midomafetamine HCl in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg offered 1.5 to 2 hrs after the initial dose, respectively.
Age, Continuous	44.3 Years STANDARD_DEVIATION 10.15 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Netherlands	8 participants n=5 Participants
Region of Enrollment Czechia	3 participants n=5 Participants
Region of Enrollment Norway	2 participants n=5 Participants
Region of Enrollment United Kingdom	6 participants n=5 Participants
Region of Enrollment Germany	2 participants n=5 Participants

PRIMARY outcome

Timeframe: 13 weeks post-baseline

Population: mITT analysis includes 1 participant who did not complete the primary outcome CAPS-5 assessment.

Outcome measures

Outcome measures
Measure	MDMA-assisted Psychotherapy n=21 Participants Open-label administration of 80 to 120 mg midomafetamine HCl in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg offered 1.5 to 2 hrs after the initial dose, respectively.
Change in CAPS-5 Total Severity Score	-13.95 score on a scale Interval -16.32 to -11.58

SECONDARY outcome

Timeframe: 13 weeks post-baseline

Population: mITT analysis includes 1 participant who did not complete the secondary endpoint SDS assessment.

The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment for PTSD. The SDS is a 3-item scale measuring the severity of disability (i.e., the degree of impairment) in the domains of work, family life/home responsibilities and social/leisure activities. Responses are recorded using an 11-point scale (0 = not at all to 10 = extremely) and 5 verbal tags (not at all, mildly, moderately, markedly, extremely). For participants who are not able to work for reasons unrelated to PTSD, the measure includes an option to skip the work-related impairment item, and the reason was collected. The impact of missing item-level data was mitigated by averaging across the items to obtain a Total Score, rather than a straight sum.

Outcome measures

Outcome measures
Measure	MDMA-assisted Psychotherapy n=21 Participants Open-label administration of 80 to 120 mg midomafetamine HCl in combination with psychotherapy, followed by a supplemental half-dose of 40 or 60 mg offered 1.5 to 2 hrs after the initial dose, respectively.
Change in Sheehan Disability Scale (SDS) Item Scores Family Life / Home	-1.18 Score on a scale Interval -2.14 to -0.22
Change in Sheehan Disability Scale (SDS) Item Scores Social / Leisure Activities	-1.45 Score on a scale Interval -2.32 to -0.58
Change in Sheehan Disability Scale (SDS) Item Scores Work / School	-1.45 Score on a scale Interval -2.36 to -0.53
Change in Sheehan Disability Scale (SDS) Item Scores Total Score	-1.30 Score on a scale Interval -2.17 to -0.43

Adverse Events

Experimental: MDMA-assisted Psychotherapy

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Experimental: MDMA-assisted Psychotherapy n=21 participants at risk Administration of 80 to 120 mg midomafetamine (MDMA) HCl in combination with manualized psychotherapy, followed by a supplemental half-dose 1.5 to 2 hrs after the initial dose of 40 or 60 mg, respectively. Midomafetamine: Non-directive psychotherapy conducted during MDMA-assisted psychotherapy session
Psychiatric disorders Suicidal ideation	4.8% 1/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Psychiatric disorders Suicidal behavior	4.8% 1/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session

Other adverse events

Other adverse events
Measure	Experimental: MDMA-assisted Psychotherapy n=21 participants at risk Administration of 80 to 120 mg midomafetamine (MDMA) HCl in combination with manualized psychotherapy, followed by a supplemental half-dose 1.5 to 2 hrs after the initial dose of 40 or 60 mg, respectively. Midomafetamine: Non-directive psychotherapy conducted during MDMA-assisted psychotherapy session
Cardiac disorders Palpitations	9.5% 2/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Eye disorders Vision blurred	9.5% 2/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Gastrointestinal disorders Nausea	38.1% 8/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Gastrointestinal disorders Vomiting	9.5% 2/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
General disorders Fatigue	19.0% 4/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
General disorders Feeling cold	9.5% 2/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
General disorders Feeling hot	9.5% 2/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Investigations Blood pressure increased	9.5% 2/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Metabolism and nutrition disorders Decreased appetite	19.0% 4/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Musculoskeletal and connective tissue disorders Muscle tightness	38.1% 8/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Musculoskeletal and connective tissue disorders Back pain	9.5% 2/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Musculoskeletal and connective tissue disorders Myalgia	14.3% 3/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Nervous system disorders Headache	71.4% 15/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Nervous system disorders Dizziness	9.5% 2/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Nervous system disorders Paraesthesia	9.5% 2/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Nervous system disorders Tension headache	9.5% 2/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Psychiatric disorders Anxiety	14.3% 3/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Psychiatric disorders Insomnia	19.0% 4/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Psychiatric disorders Suicidal ideation	33.3% 7/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Gastrointestinal disorders Dry mouth	9.5% 2/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session
Psychiatric disorders Emotional disorder	9.5% 2/21 • Approximately 8 weeks Treatment Emergent Adverse Events: Adverse events that occur during the treatment period from the first Experimental Session to the last Integrative Session

Additional Information

Berra Yazar-Klosinski, PhD / Chief Scientific Officer

Lykos Therapeutics

Phone: 877-627-7722

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place