Treatment-resistant depression (TRD). Study to be conducted in healthy volunteers Mental and Behavioural Disorders
Conditions
Interventions
This is a non-randomised, open-label study assessing the mass balance recovery, absorption, distribution, metabolism and excretion of a single dose of the test medicine. Participants will receive a si
Sponsors
Compass Pathfinder Limited
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Signed ICF. 2. Healthy Male aged 30 - 55 years at Screening. 3. Body mass index (BMI) of 18 - 32kg/m² at Screening. 4. Minimum weight of 50kg at Screening. 5. Regular bowel movements (average stool production of =1 and =3 stools per day). 6. Non-smoker (including e-cigarettes) for at least 12 months prior to Screening. 7. Willing to comply with fasting and food intake requirements. 8. Willing to comply with contraception requirements. 9. Participant is judged to have sufficient English language competence that under ordinary circumstances they are able to complete all protocol required assessments without any assistance or alteration to the copyrighted assessments, and agreement to comply with all study visits.
Exclusion criteria
Exclusion criteria: 1. Current or lifetime history of any psychotic disorder or bipolar disorder, as assessed by a structured clinical interview (Mini International Neuropsychiatric Interview, Version 7.0.2 [MINI 7.0.2] or documented via available medical records. 2. Borderline personality disorder as demonstrated by medical history or the Mini International Neuropsychiatric Interview Plus (MINI plus) – borderline personality disorder module. 3. Current or clinically relevant history of major depression, panic disorder, post-traumatic stress disorder, generalised anxiety disorder, obsessive-compulsive disorder, or eating disorder as assessed by the MINI 7.0.2 or documented via available medical records. 4. A history of suicide attempts, suicidal ideation or suicidal behaviour as determined by the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening, Day -1 or at Day 1; or clinical assessment of suicidal risk or risk of self-injury identified during other participant assessments. 5. Alcohol or substance use disorder within the 12 months prior to Screening as assessed by the MINI 7.0.2 or documented via available medical records. 6. Use of pharmacological compounds for psychiatric or neurological conditions acting on the central nervous system within the last 30 days or five half-lives (whichever is longer) prior to Screening. 7. In first-degree relatives, a history of psychotic disorders or bipolar disorder. 8. Other personal circumstances or behaviour judged by the investigator to be incompatible with the establishment of rapport or safe exposure to COMP360 [14C]-psilocybin. 9. Exposure to psilocybin, or any other classic psychedelics, such as ayahuasca, mescaline, lysergic acid diethylamide (LSD), dimethyltryptamine (DMT), 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), or peyote during the past three months prior to Screening, including microdosing. Additionally, the participant must agree not to use psychedelics for the duration of the study follow-up so as not to confound results. 10. Participants who are planning a pregnancy. 11. Participants with pregnant or lactating partners. 12. Participants who engage in sexual intercourse which could result in pregnancy, and who do not agree to use a highly effective contraceptive method throughout their participation in the study and for three months following COMP360 [14C]-psilocybin administration. 13. Participants who plan to donate sperm within the study period or within three months following COMP360 [14C]-psilocybin administration. 14. Presence of active gastrointestinal disease or other condition (eg gastrectomy, bariatric surgery, small bowel or large bowel resection) that may interfere significantly with the absorption of drugs. 15. Acute diarrhoea or constipation in the 7 days before administration of investigational medicinal product (IMP) in the study. If screening occurs >7 days before the day of administration, this criterion will be determined on the morning prior to administration. 16. Cardiovascular conditions: lifetime history of stroke, lifetime myocardial infarction, uncontrolled hypertension (resting blood pressure >140/90 mmHg), tachycardia (resting heart rate over 100 beats per minute), elongated QT interval corrected by Fridericia (QTcF; interval >450 ms) or clinically significant arrhythmia. 17. Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (defined by haemoglobin A1c [HbA1c] >8% at Screening) or a history of diabetic ketoacidosis, hyperglycaemic coma, o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluated from assessment of blood samples taken from Day 1 to Day 8: 1.Radioactivity in blood and plasma PK parameters: 1.1.Area under the concentration-time curve from zero to 24 hours (AUC0-24h) 1.2.Area under the concentration-time curve from zero to infinity (AUC0-inf) 1.3.Peak exposure (Cmax) 1.4.Time to reach peak exposure (tmax) 1.5.Time to the first measurable timepoint (tlag) 1.6.Elimination half-life (t1/2) 1.7.Last measurable concentration (Clast) The below endpoints will be evaluated through the assessment of blood samples taken from Day 1 to Day 8, and urine and faecal collections taken from Day 1 to Day 10: 2.Amount of radioactivity recovered in urine and faeces and all excreta (urine and faeces combined) as: For urine and faeces: 2.1.Ae (total radioactivity) 2.2.%Ae (total radioactivity expressed as a percentage of the dose) 2.3.Cum Ae (cumulative recovery of total radioactivity) 2.4.Cum %Ae (cumulative recovery expressed as a percentage of the dose) For all excreta combined: 2.5.Ae (total radioactivity) 2.6.% Ae (total radioactivity expressed as a percentage of the dose) 2.7.Cum Ae (total) (Cumulative recovery of total radioactivity) 2.8.Cum % Ae (total) (Cumulative recovery expressed as a percentage of the dose) 3.Metabolite profiling for plasma, urine, and faeces assessed as a single AUC pool per participant and pooled sample across all volunteers at 2 time-points. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The distribution of total radioactivity into red blood cells assessed as blood-to-plasma ratios for total radioactivity evaluated from assessment of blood samples taken from Day 1 to Day 8 The below endpoints will be evaluated through the assessment of blood samples taken from Day 1 to Day 8, and urine and faecal collections taken from Day 1 to Day 10: 2. Metabolites identified in plasma, urine and faeces samples will be structurally identified using radiochromatographic data where the metabolite represents: 2.1. Greater than 10% of the total radioactivity in plasma 2.2. Greater than 10% of the administered dose in excreta 3. Plasma PK parameters for psilocin, 4-hydroxyindoleacetic acid (4 HIAA) and psilocin-O-glucuronide: 3.1. Area under the concentration-time curve from zero to 24 hours (AUC0-24h) 3.2. Area under the concentration-time curve from zero to infinity (AUC0-inf) 3.3. Peak exposure (Cmax) 3.4. Time to reach peak exposure (tmax) 3.5. Time to the first measurable timepoint (tlag) 3.6. Elimination half-life (t1/2) 3.7. Last measurable concentration (Clast) 4. Urine PK Parameters for psilocin: 4.1. Cumulative urinary excretion in urine for eachtime interval (Ae0-t) 4.2. Fraction (% dose) excreted in urine (Fe0-t) 4.3. Maximum rate of urinary excretion (Rmax) 4.4. Time of maximal urinary excretion (TRmax) 4.5. Elimination half-life (t1/2Z) 5. Safety assessed based on adverse event, ECG, vital signs, laboratory results, C-SSRS results and BPRS+ results from Day 1 to up to Day 10. 6. Summary of the 5D-ASC scores post COMP360 [14C]-psilocybin administration on Day 1 7. Summary of the Psychedelic intensity ratings post COMP360 [14C]-psilocybin administration assessed using questionnaire results on Day 1 | — |
Countries
United Kingdom
Contacts
Public ContactZainab Alashe
Outcome results
None listed