CLINICAL STUDY PROTOCOL

Psilocybin-assisted Psychotherapy in the Management of Anxiety Associated WithStage IV Melanoma.

Version

: Final

IND

: [79,321]SPONSOR

Multidisciplinary Association for Psychedelic

PRINCIPAL INVESTIGATOR

Sameet Kumar Ph.D.

MEDICAL MONITOR

Michael C. Mithoefer MD.

STUDY PERSONNEL

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

STUDY MONITOR [CRA]

Valerie Mojeiko

IRB

Study Site IRB

Sponsor Signatory

Rick Doblin Ph.D.

Study Period

2008

For trial related

emergencies

please contact:

Dr.

 

Michael Mithoefer

 

MAPS: S Kumar PI Clinical Study Protocol PCA1Final December 1, 2007 Confidential Page 2 of 83

Table of Contents

Introduction.........................................................................................................................4Background.....................................................................................................................4Disease History and Related Research...........................................................................5Rationale.........................................................................................................................7Summary.........................................................................................................................7Ethics...................................................................................................................................8Informed Consent of Subject..........................................................................................9Recruitment and Screening.............................................................................................9Study Objectives...............................................................................................................10Primary Efficacy and Safety Objectives.......................................................................10Secondary Objectives....................................................................................................10General Investigational Plan.............................................................................................11Drug Description and Doses.........................................................................................11Sample Population and Subjects...................................................................................12Inclusion Criteria......................................................................................................12Exclusion Criteria.....................................................................................................12Planned Duration of the Study......................................................................................13Method..........................................................................................................................13Time and Events...........................................................................................................15Assessments and Measures...........................................................................................18Visit Descriptions: Psychotherapy and Assessment.........................................................19Subject Numbering.......................................................................................................19Screening and Baseline evaluation (Visits #1 to #3)....................................................20Randomized blinded Study phase.................................................................................20Randomization..........................................................................................................20Introductory Psychotherapy Session (Visits #4 and #4.5)........................................20Psilocybin-Assisted Psychotherapy (Visit #5, Visit #8)...........................................21Integrative Non-Drug Psychotherapy (Visits #6, #7 and #9)...................................23Final Evaluation in Randomized Phase (Visit #10)..................................................23Unblinding and Opportunity to Enter the Open-Label Study Segment or Two-MonthFollow-up (Visit 10).....................................................................................................24Open-Label Study Phase (Visits #11-18).....................................................................24Two-Month Follow-up (Follow-up Screening and Follow Up 1)................................25Visit by Visit Description.............................................................................................26Removal of Subjects from Therapy or Assessment......................................................30Premature Discontinuation of the Study.......................................................................30Data Analysis................................................................................................................30Statistical Power............................................................................................................32Monitoring for Risks.........................................................................................................32Acute Psychological Distress........................................................................................33Medical Emergencies....................................................................................................34Serious Adverse Events................................................................................................35Adverse Event Collection.............................................................................................36Collection of Concomitant Medications.......................................................................37

 

MAPS: S Kumar PI Clinical Study Protocol PCA1Final December 1, 2007 Confidential Page 3 of 83

Laboratory Assessments...............................................................................................37Study Monitoring, Auditing and Documentation.........................................................37Risks to Participants..........................................................................................................37Risks and Discomforts Related to Screening and Baseline Examination.....................37Risks and Discomforts of Psychotherapy.....................................................................38Risk of the Experimental Drug (psilocybin).................................................................38Panic attacks, severe generalized anxiety, or persisting insomnia............................39Reckless or self-injurious behavior...........................................................................39Psychosis, suicidal thoughts or impulses..................................................................40Chronic neuropsychological effects..........................................................................40Reproductive and Developmental Risks.......................................................................41Potential for Drug/ Drug Interactions.......................................................................41Abuse Liability..........................................................................................................42Risks of Active Placebo dose of Psilocybin.................................................................42Alternative Treatments and Procedures............................................................................42Confidentiality..................................................................................................................43Costs to Participants..........................................................................................................43Risk/Benefits Analysis......................................................................................................43Patient’s Rights/Insurance................................................................................................44Record Retention..........................................................................................................45Chemistry, Manufacturing and Control Information........................................................45Pharmacokinetics and Pharmacodynamics.......................................................................45Primary Pharmacology..................................................................................................45Primary Pharmacodynamics.........................................................................................46Drug Activity Related to Proposed Action...............................................................46Secondary Pharmacology..............................................................................................47Safety Pharmacology................................................................................................47Common side effects.................................................................................................48Acute Adverse Effects..............................................................................................49Abuse Liability..........................................................................................................50Pharmacokinetics/Toxicokinetics.................................................................................51Absorption, Distribution, Metabolism, Excretion.....................................................51Toxicology....................................................................................................................51Acute toxicity............................................................................................................51Reproductive Toxicity..............................................................................................51Previous Human Experience.........................................................................................52Additional Information.................................................................................................54Facilities and Setting of Study..................................................................................54Drug Dependence and Abuse Potential....................................................................54References.........................................................................................................................55Appendix A Asssessments and Measures.........................................................................62Appendix B: Case Report Forms......................................................................................65