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MP-7 Investigator Meeting January 31, 2011

MP-7 Investigator Meeting January 31, 2011. Berra Yazar- Klosinski Kamila Novak. MP-7 Team. Site Principal Investigator: Nasser Shuriquie MD Co-therapists: Tayseer Shawash MD, Mona Al- Nsour PhD, Malak Talep abu Hdaib CRO Regional Manager: Kamila Novak

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MP-7 Investigator Meeting January 31, 2011

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  1. MP-7 Investigator MeetingJanuary 31, 2011 Berra Yazar-Klosinski Kamila Novak

  2. MP-7 Team Site • Principal Investigator: Nasser Shuriquie MD • Co-therapists: TayseerShawash MD, Mona Al-Nsour PhD, MalakTalepabuHdaib CRO • Regional Manager: Kamila Novak • Clinical Research Associate: Doaa Al-Faqih Sponsor • Clinical Program Manager: Amy Emerson • Clinical Research Associate: Berra Yazar-Klosinski, PhD • Executive Director: Rick Doblin, PhD • Medical Monitor: Michael Mithoefer, MD

  3. Objectives • MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD • Explore safety and efficacy • Determine effect size for this subject population • Assess if investigators and participants accurately guess MDMA dose condition • Primary Objective • Assess changes in PTSD symptoms via CAPS* score at baseline and end of Stage 1 * CAPS = Clinician Administered PTSD Scale

  4. Secondary Objectives • Assess: • Before and after Stage 1 in all dose conditions • Quality of life by GAF* • Symptoms of depression by BDI-II** scores • After open-label lead-in (CAPS, GAF, BDI-II) • After Stage 2 cross over (CAPS, GAF, BDI-II) • At the the 12 month follow-up (CAPS, GAF, BDI-II) * GAF = Global Assessment of Functioning ** BDI-II = Beck Depression Inventory - II

  5. Efficacy Variables- Outcome Measures • Primary efficacy measure:CAPS • Measures overall PTSD severity • Covers 4 symptom clusters • Evaluates frequency and intensity dimensions of each symptom cluster • Measures impact of symptomson social and occupational functioning • CAPS interviews determined to have • Good internal consistency • Concurrent validity • Test/retest reliability • CAPS has been translated into Arabic for first time for the study

  6. Efficacy Variables- Outcome Measures • GAF • Measures Quality of life • General function • Scores from 0 to 100 • 100 = superior function • 0 = serious risk of causing harm to self or others • BDI-II • 21-item measure of depressive symptoms • Self-report: completed by subject • Previous studies used and validated in Arabic

  7. Safety Objectives • To monitor and assure safety of participants by assessing: • Psychological distress with SUD* during each experimental session • Vital signs during each experimental session • Suicidality with C-SSRS** • Before, during and after experimental sessions • Adverse Events (AEs), Serious Adverse Events (SAEs) and Spontaneously ReportedReactions * SUD = Subjective Units of Distress ** C-SSRS = Columbia Suicide Severity Rating Scale

  8. Safety Variables • Subjective Units of Distress Scale (SUD) • Current degree of distress according to subject • Single item • Self-report: completed by subject • Measured every 60-90 minutes during experimental session • Vital signs • More frequent measures if one of following thresholds are exceeded: • 160 mmHg systolic BP • 110 mm Hg diastolic BP • 110 bpm heart rate • Blood pressure • Measured every 30 minutes during experimental session • Heart rate • Measured every 30 minutes during experimental session • Body temperature • Measured every 60-90 minutes during experimental session

  9. Safety Variables • C-SSRS • Measure of suicidal behavior • Detects potential suicidal thoughts or behaviors during a clinical trial • Face to face interview • Over the telephone • Adverse Events (AEs) and spontaneously reported reactions • Collected during experimental sessions and for 7 days after • Serious adverse events (SAEs) • Concomitant Medications

  10. Process Measures • The Reactions to Research Participation Questionnaire (RRPQ) • Assesses participant’s experience as a research subject • Reasons for consenting to be a research participant • Perceived freedom to take part in the study • Self-report: completed by subject • Translated to Arabic for the study • Belief of condition assignment • Subject, investigators and Independent Rater try to guess condition assignment during Stage 1 • How certain they are is also recorded

  11. Patient Population and Recruitment • Patients: 12 people • Chronic, treatment-resistant PTSD (CAPS ≥ 50 at baseline) • At least 18 years old • Recruitment: • Hospital database • Letters of referral • To psychiatrists or psychotherapists • Word of mouth • Iraqi refugees

  12. Inclusion Criteria • Meet DSM IV criteria for current PTSD • 6 months or longer • CAPS score of 50 or higher • Indicating moderate to severe PTSD • At least one unsuccessful attempt at treatment • With medication (SSRI, SNRI, mirtazapine, MAOI) or psychotherapy • At least 18 years old • Willing to commit to medication dosing, experimental sessions, follow-up sessions and complete evaluation instruments • Willing to refrain from taking psychiatric medications during study • Except gabapentin for pain control • Discontinue only after consultation with prescribing physician

  13. Inclusion Criteria • Agree not to change type or frequency of current psychotherapy or outside therapist until after 3rd experimental session • For one week preceding experimental session, refrain from: • Any herbal supplement • Any nonprescription medications (exeptNSAIDs or Acetaminophen) • Any prescription medications (except birth control, thyroid hormones) • Get approval from research team for additional exceptions • Evening before experimental session after 24:00 (midnight) • Nothing by mouth except alcohol-free liquids • Refrain from the use of any psychoactive drug (except nicotine or caffeine), within 24 hours of each MDMA session • no use of nicotine and caffeine 1 hour before and 3 hours after MDMA administration

  14. Inclusion Criteria • Willing to remain overnight at study site after each experimental session until after integrative session next morning • Willing to be driven home the morning after the experimental sessions, after integrative session, either by a driver arranged by the subject, or by site personnel or taxi • Willing to be contacted via telephone on a daily basis by one of the investigators for a week after each experimental session • If female subject able to bear children • Willing to have pregnancy tests • Use effective form of birth control • Literate, proficient in speaking and reading Arabic, able to effectively communicate with therapists and other site personnel • Willing not to participate in any other clinical trials during the duration of this study, including the follow-up period

  15. Exclusion Criteria • Pregnant or nursing • Women of child bearing potential who are not practicing an effective means of birth control (including abstinence) • History of, or current: • Primary psychotic disorder • Bipolar affective disorder type 1 • Dissociative identity disorder • Borderline personality disorder • Eating disorder with active purging • Evidence or history of significant: • Hematological, Endocrine, Cerebrovascular, Cardiovascular • Coronary, Pulmonary, Renal, Gastrointestinal • Immunocompromising, Neurological disease, Seizure disorder

  16. Exclusion Criteria • Hypertension, peripheral vascular disease • Hepatic disease (with or without abnormal liver enzymes) • History of hyponatremiaorhyperthermia • Weighlessthan 48 kg • Have used “Ecstasy” (illicit drug preparationsthatmaycontain MDMA) • > 5 timestotal, or • Within last 6 months • Serious suicide risk, or likely to require hospitalization during study

  17. Exclusion Criteria • Require ongoing concomitant therapy with psychiatric drug • E.g. SSRIs, SNRIs, MAOIs • Meet DSM-IV criteria for substance abuse within last 60 days • Not including caffeine and nicotine • Not able to give adequate informed consent • Current problem or history of substance abuse which might interfere with participation in the protocol

  18. Study Design • This is a randomized, double-blind, dose comparison study with: • Open-label lead-in section • Randomized, blinded arm (Stage 1) • Open-label partial cross-over arm: only Active Placebo subjects cross over (Stage 2) • Open-label lead-in: training on the treatment method (2 subjects) • Similar to Stage 1 (3 prep sessions) • Similar to Stage 2 (open-label, full dose) • 1st subject: 3 experimental sessions complete with video • 2nd subject: 2 experimental sessions complete with video • Sponsor reviews data for adherence: 3 out of 5 sessions above • After approval, then proceed with Stage 1

  19. Randomization • Stage 1: blinded assignment to two dose conditions • 40 mg (active placebo dose)+ optional 20 mg supplement (3 subjects) • 125 mg (full dose) + optional 62.5 mg supplement (7 subjects) • Web-based randomization • detailed instructions in Study Reference Manual • Participants are randomized at least 24 hours before first experimental session • Stage 2: open-label full dose condition • 125mg (full dose) + optional 62.5 mg supplement (8 subjects)

  20. MP-7 Flowchart- Exp Session 1 Preparatory Sessions Experimental Session 1 Visit 1 Enroll Screening 5 Randomize 2 3 4 Approximately 1 week apart 3-5 weeks after V1 and 3 prep sessions Baseline Evaluation Ind. Rater

  21. MP-7 Flowchart- Exp Session 2 Experimental Session 1 Experimental Session 2 Integrative Sessions Integrative session 1 day after 9 5 7 8 6 7 day phone follow up 3-5 weeks after Exp session 1 and 3 integrative sessions Approximately 1 week apart

  22. MP-7 Flowchart- Exp Session 3 Experimental Session 2 Experimental Session 3 Integrative Sessions Integrative session 1 day post 13 9 10 11 12 7 day phone follow up 3-5 weeks after Exp session 2 and 3 integrative sessions Approximately 1 week apart

  23. MP-7 Flowchart- End of Stage 1 Outcome, unblinding and possible enrollment in Stage 2 Integrativesessions Experimental Session 3 Integrative session 1 day post 13 17 14 15 16 7 day phone follow up Approximately 1 week apart Outcome Ind. Rater 2 months after Exp session 3

  24. Stage 2 – Open Label Crossover • Only Active Placebo subjects eligible • Course and schedule is similar to Stage 1 & lead-in • Confirm informed consent & willingness to continue • Confirm eligibility criteria • 1 preparatorypsychotherapysession – V18 • All Stage 2 subjectswillreceive full dose MDMA • Dropoutswillnotbereplaced, max 3 subjects

  25. MP-7 Flowchart- Long Term Follow Up Final Experimental Session (Stage 1 or Stage 2) Long Term Follow-up Evaluation 1 year Memory aids Psychiatric medications Outcome Ind. Rater 2 months after Exp session 3 (Stage 1 or Stage 2) Outcome Ind. Rater 12 months after final Exp session

  26. Screening • Screening Visits • Completed during 1 month prior to Visit 1 • Collect psychiatric & medical history • Complete physical exams, clinical labs • Review previous medical records or talk with treating physician if needed to clarify medical history • Review Inclusion Exclusion • Schedule Independent Rater Baseline Screening Discussion: What is the best way to communicate and provide information about subjects between the Rater and the Investigator? How to complete and share source records Video recording

  27. Study Procedures and Source records • Preprinted Source Records for visits are provided • Source cover sheets and checklists are provided to the Independent Rater • Independent Rater Checklist • Checklists and outcome measure results will be sent over in packets at the time each subject is enrolled or progresses to Stage 2 and/or Follow-up • Completed Outcome Measures are the source for independent rater assessments • The source will be used to complete CRFs. The CRFs will be monitored and entered into the MAPS database

  28. Memory Aid Card • Tool for subject to record adverse events and safety information during the 10 months after the final Independent Rater assessment • Memory Aids will not be collected • Info may be collected by phone or in person • The Memory Aids are designed to help the subject recall • any AEs/SAEs and medications associated with these • If and when they started psychiatric medications

  29. Long Term Follow-up and Study Termination • Subjects complete the 2 month outcome measures following the final experimental session and enter long term follow up. • Complete RRPQ right before follow-up period • Give a memory aid card to help with safety collection during the 10 month period until termination • At 12 months after the final experimental session they will be contacted to have final outcome measures completed and a final visit with the therapists

  30. Early Termination • Subjects can withdraw consent at any time • Investigators can withdraw a subject in his/her clinical judgment if: • The safety of the study subject is impacted • The subject cannot comply with the protocol • Due to contraindications • Withdrawn subjects in Stage 1 will be replaced

  31. Withdrawal of Subjects from Trial and Replacement Procedures • If a subject terminates from treatment and does not withdraw consent they should be followed for safety and proceed to follow up visits as applicable • Complete the next integrative session(s) and complete final outcome measure as appropriate • Inform Randomization Monitor of withdrawal via email • Replacement subjects will receive new Enrollment Code

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