E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alcohol use disorder (AUD) |
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E.1.1.1 | Medical condition in easily understood language |
Alcohol use disorder (AUD) |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10080021 |
E.1.2 | Term | Alcohol use disorder |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the trial is to evaluate the efficacy of 25 mg Psilocybin vs Placebo in subjects with alcohol use disorder (AUD) with number of heavy drinking days (HDD) over the 8-week treatment period, measured on a monthly basis relative to baseline (Visit 1 - 5). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this trial are to assess the effects of 25 mg psilocybin vs placebo on the following endpoints: • Monthly number of HDD at V5(baseline), Week 4, 8, 12, 16, 20, and 24. • Monthly total alcohol consumption (TAC), defined as the mean daily alcohol consumption expressed in g/day at V5 (baseline), Week 4, 8, 12, 16, 20 and 24. • Proportion of subjects with no HDD per month at Week 8, 12, 16, 20, and 24. • Proportion of subjects with one- or two-level reductions in the WHO Risk Drinking Levels per month at Week 8 and 12. • DSM-5 score at V1 vs V13 (Week 24) Safety as measured by • The incidence and severity of adverse events (AEs) treatment emergent adverse events (TEAEs), serious adverse events (SAEs) and the number of subjects withdrawn from the trial due to a TEAE. • Clinical safety parameters including physical examination, body weight, vital signs, and clinical laboratory investigations. • Psychedelic experience during the psychotherapy sessions. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Moderate to severe diagnosis of AUD as measured by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria using Structured Clinical Interview for DSM-5 by the investigator.
• A subject is eligible for participation in the trial if he/she/they (sex at birth) had: a. ≥6 HDDs (defined as a day with alcohol consumption of 60 g or more for males and 40 g or more for females) in a 4-week period prior to V1 (TLFB) OR an average alcohol consumption of >40 g of ethanol/day for males and >20 g of alcohol/day for females for a 4-week period prior to V1 (TLFB), [minimum of the medium risk level as defined by the WHO "International therapist for monitoring alcohol consumption and related harm."] AND b. ≥6 HDDs (defined as a day with alcohol consumption of 60 g or more for males and 40 g or more for females) in a 4-week period prior to V5 (e-diary),
• Expressed a wish to reduce or stop alcohol consumption.
• Able to provide alcohol consumption information for the 4-week period prior to V1.
• Willingness to participate in behavioural and medicinal treatments for AUD.
• Subjects of childbearing potential must be using a highly effective, established method of contraception for the entire trial duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices. Note: Subjects identified female-at-birth who are surgically sterilised (bilateral salpingectomy, or bilateral oophorectomy)/hysterectomised at least 3 months before V1 or post-menopausal for longer than 2 years are not considered as being of childbearing potential. Male subjects who engage in sex that could result in pregnancy should use condom with spermicide throughout their trial participation in addition to the use of a highly effective contraceptive method by any partner of childbearing potential.
• Generally healthy with no unstable medical conditions, as determined by medical history, physical examination, routine blood labs, electrocardiogram, urine analysis, and urine toxicology.
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E.4 | Principal exclusion criteria |
• Withdrawal symptoms requiring additional medication defined as a score higher than 8 on the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar).
• Diagnosed with or having a family history of any of the following concomitant psychiatric disorders: schizophrenia or prodromal symptoms, any bipolar disorder, obsessive compulsive disorder, or other psychotic disorder. Recent (within last 12 months) diagnosis of a major depressive episode (MDD) (as according to Hamilton Depression Scale, HAM-D, score >19), treatment resistant depression (TRD), post-traumatic stress disorder (PTSD), panic disorder or eating disorders. Note: Subjects with nicotine use disorder, phobic, or other anxiety disorders (other than post-traumatic stress disorder or panic disorder) can be included.
• Current or recent (within 6 weeks prior to V1) treatment with antipsychotic or antidepressant medications, which can influence serotonin receptor or transporter actions.
• History of hallucinogen use disorder, or any use in the past 1 year, or >25 lifetime uses.
• Currently participating or has recently (4 weeks prior to V1) participated in a treatment program for AUD.
• Clinically significant untreated or unstable illness as defined by a. Hepatic function: • Aspartate aminotransferase (AST) >3x the upper limit of normal (ULN) or •Alanine aminotransferase (ALT) >3x the upper limit of normal (ULN) or • Total bilirubin >2x ULN • Prolonged prothrombin time (PTT) INR ≥1.7 b. Renal function: • Reduced estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m2. c. Cardiovascular functions: • History or current evidence of a clinically significant cardiovascular disease, including myocardial infarction, cerebrovascular accident, unstable angina, New York Heart Association Class II or greater heart failure, severe cardiac arrhythmia requiring medication or implanted defibrillator or pacemaker, syncope. •Uncontrolled hypertension, defined by systolic blood pressure >150 mmHg and/or diastolic blood pressure >90 mmHg (measured while subject is lying supine over a 5-minute duration. If necessary, these assessments will involve three readings separated by 5 minutes) with or without antihypertensive medications; or clinically significant hypotension. • Finding of any of the following on the V1 ECG: QT interval corrected using Fridericia’s formula (QTcF) >450 msec (males) and >470 msec (females), frequent supraventricular or ventricular ectopy, complete right and left bundle branch block (QRS >110 ms), or any other ECG findings that, in the opinion of the Investigator is regarded as abnormal.
• Allergy, hypersensitivity, or other adverse reaction to previous use of psilocybin, other hallucinogens, rescue medications and their excipients or microcrystalline cellulose.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for analysis of efficacy is defined as • Mean number of HDD from V5 (baseline) measured monthly (4 weeks) over the treatment period (Week 8), where heavy drinking is defined as the consumption of ≥60 g alcohol/day (if male) or ≥40 g alcohol/day (if female).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From V5 (baseline) measured monthly (4 weeks) over the treatment period (Week 8) |
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E.5.2 | Secondary end point(s) |
The secondary endpoints of this trial are the following: • Change from V5 in the monthly (4 weeks) number of HDD at Week 4, 8, 12, 16, 20, and 24. • Change from V5 in monthly TAC up to Week 24. • Proportion of subjects with no HDD per month at Week 8, 12, 16, 20, and 24. • Proportion of subjects with one- or two-level reductions in the WHO Risk Drinking Levels up to Week 24. • Proportion of subjects whose DSM-5 score has improved between V1 and V13 (Week 24).
Safety endpoints: • The incidence and severity of AEs, TEAEs, SAEs, and the number of subjects withdrawn from the trial due to a TEAE. • Clinical safety parameters based on physical examination, body weight, vital signs, and clinical laboratory. • Psychedelic experience during the psychotherapy sessions as measured by the 5-Dimensional Altered States of Consciousness Scale (5D-ASCS), Mystical Experience Questionnaire (MEQ), and Therapy Evaluation Form.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• HDD: at V5, week 4, 8, 12, 16, 20, and 24. • TAC: at V5, Week 4, 8, 12, 16, 20, and 24. • HDD per month: at Week 8, 12, 16, 20, and 24 • WHO Risk Drinking Levels per month: up to Week 24 • DSM-5 score: V1, V13 (Week 24) • Physical examination: V1, V5, V10. • Body weight: V1, V10. • Vital signs: V1, V5-V10. • Clinical laboratory: V1, V5, V10. • 5D-ASCS, Mystical Experience Questionnaire, and Therapy Evaluation Form: V6, V8.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |