Clinical trial NCT06643637: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of MLS101 in Healthy Participants
Official title: A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of MLS101 (Psilocybin) in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: MycoMedica Life Sciences PBC
Sponsor class: INDUSTRY
First posted: 2024-10-16
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, double-blind, placebo-controlled multiple dose study to assess the safety, tolerability, and pharmacokinetics of MLS101 in healthy participants.

Multiple Dose (MD): 16 participants will be enrolled in two dose cohorts and will be randomized to receive multiple doses of MLS101 or placebo. An additional cohort (8 participants) may enrolled to explore more doses.
Primary purpose: TREATMENT

Brief summary: MLS101 is being developed as a low dose psilocybin, that can be administered to treat neurological and psychiatric conditions.

The purpose of this clinical trial is to assess how safe and tolerated MLS101 is; to see how MLS101 is distributed and cleared by the body (pharmacokinetics); and to assess the psychedelic effects of MLS101 in healthy, adult participants.

Detailed description: In recent years, high-dose psilocybin has gained attention for it potential therapeutic benefit in many psychiatric conditions, however existing clinical data for low psilocybin doses are limited.

Microdoses are generally considered to be those absent of profound sensory and cognitive effects that would interfere with normal everyday functioning, but only a small number of prospective studies have evaluated microdoses and/or low doses in a controlled manner.

As a foundational study of the therapeutic use of psilocybin microdoses, this study will assess the safety, tolerability, pharmacokinetics and sensorial effects using a prospective, controlled, multiple dose regimen in healthy volunteers.

Eligibility criteria: Inclusion Criteria:

1. Males or females aged 18 to 65 years old (inclusive) at the time of signing the informed consent form. Standard contraception measures are required for this clinical trial.
2. Healthy, in the opinion of the Investigator, based on prior (history of) or current (ongoing) medical and psychiatric screening assessments.
3. Participants with no clinically significant findings on physical examination, laboratory tests, and cardiac assessment.
4. Body mass index (BMI) within the range 18-32 kg/m2, inclusive.
5. Normal blood pressure.
6. Capable of giving signed informed consent which includes the requirements and restrictions as per the approved study protocol.

Exclusion Criteria:

1. Prior known exposure to psilocybin within the past 5 years.
2. Prior (history of) or current (ongoing) diagnosis, or first-degree relatives with clinically significant medical or psychiatric condition or disease.
3. History of or presence of cardiovascular disease.
4. Abnormal and clinically significant ECG.
5. History or presence of a neurodegenerative disorder such Alzheimer's disease or Parkinson's disease.
6. Use of medications that have CNS effects or affect performance.
7. Use of medications with serotonergic activity.
8. History or presence of hypersensitivity or idiosyncratic reaction to psilocybin or related compounds.
9. History of substance or alcohol abuse disorder in the last 1 year.
10. Participant who, for any reason, is deemed by the Investigator to be inappropriate for this study; or has any condition which would confound or interfere with the evaluation of the safety, tolerability, or PK of the investigational drug; or is unable to comply with the study protocol.

Primary outcomes:
measure: Incidence, severity and seriousness of treatment-emergent adverse events (TEAEs)
timeFrame: Screening (Day -28) to end of study visit (Cohort 1: Day 15; Cohort 2: Day 23)
measure: Occurrence of clinically significant changes in physical examination, vital signs, ECGs, clinical laboratory tests, the Columbia-Suicide Severity Rating Scale (C-SSRS).
timeFrame: Screening (Day -28) to end of study visit (Cohort 1: Day 15; Cohort 2: Day 23)
Secondary outcomes:
measure: Pharmacokinetics of MLS101: maximum observed serum concentration (Cmax)
timeFrame: Day 1 to Day 8 pre-dose, Day 1 to Day 9 post-dose (Cohort 1); Day 1 to Day 16 pre-dose, Day 1 to Day 17 post-dose (Cohort 2)
measure: Pharmacokinetics of MLS101: area under the plasma concentration-time curve (AUC)
timeFrame: Day 1 to Day 8 pre-dose, Day 1 to Day 9 post-dose (Cohort 1); Day 1 to Day 16 pre-dose, Day 1 to Day 17 post-dose (Cohort 2)
measure: Pharmacokinetics of MLS101: time corresponding to the occurrence of Cmax (Tmax)
timeFrame: Day 1 to Day 8 pre-dose, Day 1 to Day 9 post-dose (Cohort 1); Day 1 to Day 16 pre-dose, Day 1 to Day 17 post-dose (Cohort 2)
measure: Pharmacokinetics of MLS101: apparent terminal elimination half-life (t½)
timeFrame: Day 1 to Day 8 pre-dose, Day 1 to Day 9 post-dose (Cohort 1); Day 1 to Day 16 pre-dose, Day 1 to Day 17 post-dose (Cohort 2)
measure: Pharmacokinetics of MLS101: apparent total systemic clearance after oral administration (CL/F)
timeFrame: Day 1 to Day 8 pre-dose, Day 1 to Day 9 post-dose (Cohort 1); Day 1 to Day 16 pre-dose, Day 1 to Day 17 post-dose (Cohort 2)
measure: Pharmacokinetics of MLS101: apparent volume of distribution during the terminal phase (Vz/F)
timeFrame: Day 1 to Day 8 pre-dose, Day 1 to Day 9 post-dose (Cohort 1); Day 1 to Day 16 pre-dose, Day 1 to Day 17 post-dose (Cohort 2)
measure: Sensorial effects of MLS101
timeFrame: Day 1 to Day 8 pre- and post-dose (Cohort 1); Day 1 to Day 16 pre- and post-dose (Cohort 2)
measure: Cognitive function: Digit Symbol Substitution Test (DSST)
timeFrame: Pre-dose (Day -1), Day 1, Day 4 and Day 8 (Cohort 1); Pre-dose (Day -1), Day 1, Day 4 and Day 16 (Cohort 2)
measure: Cognitive Function: Stroop Color and Word Test (SCWT)
timeFrame: Pre-dose (Day -1), Day 1, Day 4 and Day 8 (Cohort 1); Pre-dose (Day -1), Day 1, Day 4 and Day 16 (Cohort 2)
measure: Cognitive function: Trail Making Test A (TMT-A)
timeFrame: Pre-dose (Day -1), Day 1, Day 4 and Day 8 (Cohort 1); Pre-dose (Day -1), Day 1, Day 4 and Day 16 (Cohort 2)
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: CMAX Clinical Research
state: South Australia
Study officials:
References: