Pharmacokinetics, Safety, and Tolerability of Intramuscular 5-MeO-DMT in Healthy Volunteers

Study Overview
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Brief Summary
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The primary objective of the study is to assess the pharmacokinetics, safety, and tolerability of a single-dose and multiple-doses of 5-MeO-DMT administered by intramuscular (IM) injections in healthy subjects.

Detailed Description
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This study is a phase 1, first-in-human, double-blind, placebo-controlled, randomized, single-dose and multiple-ascending-dose study of 5-MeO-DMT administered by intramuscular injection in 54 healthy subjects (adult male and/or females, 18-65 years of age). Subjects will be randomized 6:1 to receive 5-MeO-DMT or placebo.

Official Title
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A Phase 1, First-in-human, Double-blind, Placebo-controlled, Randomized, Single- and Multiple-ascending-dose Study to Determine the Safety, Tolerability, and Pharmacokinetics of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) Administered by Intramuscular Injection in Healthy Subjects

Conditions
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Pharmacokinetics, Safety, Tolerability

Intervention / Treatment
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* Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult male or female. Aged at least 18 years but not older than 65 years, inclusive. Body mass index (BMI) within 18.0 kg/m2 to 32.0 kg/m2, inclusive. Exclusion Criteria: History of significant hypersensitivity to the IP or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, or endocrine disorders, as determined by the investigator (or designee). Participants who, in the opinion of the investigator (or designee), should not participate in this study. Participant is participating in another study with a medical device or IP within the last 30 days prior to first study drug administration.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This study will include separate single- and multiple-dose parts. Single-dose part: A double-blind, placebo-controlled, randomized, sequential-group design with 5-MeO-DMT administered by intramuscular injection in 6 cohorts of 6 subjects (randomized as 5 active and 1 placebo subject(s) per group). Multiple-dose part: A double-blind, placebo-controlled, randomized, sequential-group design with 5-MeO-DMT administered by intramuscular injection in up to two doses within a single day (3-hour interval) with two different dose levels (6 subjects per group).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - 0.5 mg single-dose<br>A single 0.5 mg 5-MeO-DMT or placebo dose administered intramuscularly (randomized as 5 active and 1 placebo subject). | Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt<br>* The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.<br>* Other names: 5-MeO-DMT;Drug: Placebo<br>* The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.<br>* Other names: 0.9% sodium chloride solution (USP);|
| Experimental: Cohort 2 - 2.5 mg single-dose<br>A single 2.5 mg 5-MeO-DMT or placebo dose administered intramuscularly (randomized as 5 active and 1 placebo subject). | Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt<br>* The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.<br>* Other names: 5-MeO-DMT;Drug: Placebo<br>* The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.<br>* Other names: 0.9% sodium chloride solution (USP);|
| Experimental: Cohort 3 - 4.5 mg single-dose<br>A single 4.5 mg 5-MeO-DMT or placebo dose administered intramuscularly (randomized as 5 active and 1 placebo subject). | Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt<br>* The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.<br>* Other names: 5-MeO-DMT;Drug: Placebo<br>* The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.<br>* Other names: 0.9% sodium chloride solution (USP);|
| Experimental: Cohort 4 - 7 mg single-dose<br>A single 7 mg 5-MeO-DMT or placebo dose administered intramuscularly (randomized as 5 active and 1 placebo subject). | Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt<br>* The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.<br>* Other names: 5-MeO-DMT;Drug: Placebo<br>* The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.<br>* Other names: 0.9% sodium chloride solution (USP);|
| Experimental: Cohort 5 - 10 mg single-dose<br>A single 10 mg 5-MeO-DMT or placebo dose administered intramuscularly (randomized as 5 active and 1 placebo subject). | Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt<br>* The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.<br>* Other names: 5-MeO-DMT;Drug: Placebo<br>* The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.<br>* Other names: 0.9% sodium chloride solution (USP);|
| Experimental: Cohort 6 - 13 mg single-dose<br>A single 5-MeO-DMT 13 mg or placebo dose administered intramuscularly (randomized as 5 active and 1 placebo subject). | Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt<br>* The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.<br>* Other names: 5-MeO-DMT;Drug: Placebo<br>* The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.<br>* Other names: 0.9% sodium chloride solution (USP);|
| Experimental: Cohort 7 - multiple-dose, 3 hour interval<br>Administration of up to two 5-MeO-DMT (2.5 mg followed by 4.5 mg) or placebo doses administered intramuscularly within a single day with a 3 hour dose interval (randomized as 5 active and 1 placebo subject). | Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt<br>* The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.<br>* Other names: 5-MeO-DMT;Drug: Placebo<br>* The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.<br>* Other names: 0.9% sodium chloride solution (USP);|
| Experimental: Cohort 8 - multiple-dose, 3 hour interval<br>Administration of up to two 5-MeO-DMT (2.5 mg followed by 7 mg) or placebo doses administered intramuscularly within a single day with a 3 hour dose interval (randomized as 5 active and 1 placebo subject). | Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt<br>* The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.<br>* Other names: 5-MeO-DMT;Drug: Placebo<br>* The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.<br>* Other names: 0.9% sodium chloride solution (USP);|
| Experimental: Cohort 9 - multiple-dose, 3 hour interval<br>Administration of up to two 5-MeO-DMT (2.5 mg followed by 10.5 mg) or placebo doses administered intramuscularly within a single day with a 3 hour dose interval (randomized as 5 active and 1 placebo subject). | Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt<br>* The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.<br>* Other names: 5-MeO-DMT;Drug: Placebo<br>* The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.<br>* Other names: 0.9% sodium chloride solution (USP);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Treatment Emergent Adverse Events as coded by MedDRA and assessed by CTCAE v4.0 | Number of participants with TEAEs following administration of 5-MeO-DMT. | Up to 30 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetic parameters of 5-MeO-DMT and bufotenine following a single-dose and multiple-doses of 5-MeO-DMT | For PK analysis, blood samples will be collected before and up to 24 hours after the intramuscular administration of 5-MeO-DMT to determine 5-MeO-DMT and bufotenine serum concentrations. | Up to 24 hours | 
| Urine pharmacokinetic parameters of 5-MeO-DMT and bufotenine following a single-dose and multiple-doses of 5-MeO-DMT | For PK analysis, urine samples will be collected before and up to 24 hours after the intramuscular administration of 5-MeO-DMT to determine 5-MeO-DMT and bufotenine urine concentrations. | Up to 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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5-MeO-DMT, Psychedelics, Safety, Pharmacokinetics, First-in-human, 5-methoxy-N,N-dimethyltryptamine