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Berra Yazar-Klosinski Kamila Novak. Site  Principal Investigator: Nasser Shuriquie MD  Co-therapists: Tayseer Shawash MD, Mona Al-Nsour PhD, Malak Talep.

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Presentation on theme: "Berra Yazar-Klosinski Kamila Novak. Site  Principal Investigator: Nasser Shuriquie MD  Co-therapists: Tayseer Shawash MD, Mona Al-Nsour PhD, Malak Talep."— Presentation transcript:

1 Berra Yazar-Klosinski Kamila Novak

2 Site  Principal Investigator: Nasser Shuriquie MD  Co-therapists: Tayseer Shawash MD, Mona Al-Nsour PhD, Malak Talep abu Hdaib 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  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  Assess: o Before and after Stage 1 in all dose conditions  Quality of life by GAF*  Symptoms of depression by BDI-II** scores o After open-label lead-in (CAPS, GAF, BDI-II) o After Stage 2 cross over (CAPS, GAF, BDI-II) o At the the 12 month follow-up (CAPS, GAF, BDI-II) * GAF = Global Assessment of Functioning ** BDI-II = Beck Depression Inventory - II

5  Primary efficacy measure: CAPS ◦ Measures overall PTSD severity ◦ Covers 4 symptom clusters ◦ Evaluates frequency and intensity dimensions of each symptom cluster ◦ Measures impact of symptoms on 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  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  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 Reported Reactions * SUD = Subjective Units of Distress ** C-SSRS = Columbia Suicide Severity Rating Scale

8  Subjective Units of Distress Scale (SUD) ◦ Current degree of distress according to subject ◦ Single item ◦ Self-report: completed by subject ◦ Measured every 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 minutes during experimental session

9  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  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  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  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  Agree not to change type or frequency of current psychotherapy or outside therapist until after 3 rd experimental session  For one week preceding experimental session, refrain from: ◦ Any herbal supplement ◦ Any nonprescription medications (exept NSAIDs 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  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  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  Hypertension, peripheral vascular disease  Hepatic disease (with or without abnormal liver enzymes)  History of hyponatremia or hyperthermia  Weigh less than 48 kg  Have used “Ecstasy” (illicit drug preparations that may contain MDMA) ◦ > 5 times total, or ◦ Within last 6 months  Serious suicide risk, or likely to require hospitalization during study

17  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  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) ◦ 1 st subject: 3 experimental sessions complete with video ◦ 2 nd 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  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 Screening Experimental Session 1 Preparatory Sessions Approximately 1 week apart Randomize Visit 1 Enroll Baseline Evaluation Ind. Rater 3-5 weeks after V1 and 3 prep sessions

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

22 9 7 day phone follow up Experimental Session 2 Experimental Session 3 Integrative session 1 day post Integrative Sessions Approximately 1 week apart 3-5 weeks after Exp session 2 and 3 integrative sessions

23 13 7 day phone follow up Integrative sessions Outcome Ind. Rater 2 months after Exp session 3 17 Outcome, unblinding and possible enrollment in Stage 2 Experimental Session 3 Approximately 1 week apart Integrative session 1 day post

24  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 preparatory psychotherapy session – V18  All Stage 2 subjects will receive full dose MDMA  Dropouts will not be replaced, max 3 subjects

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

26  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  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  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  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 Long Term Follow-up and Study Termination

30 ◦ 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  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  Replacement subjects will receive new Enrollment Code


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