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

• ClinicalTrials.gov Identifier: NCT05698095
• Recruitment Status: Recruiting
• First Posted: January 26, 2023
• Last Update Posted: January 26, 2023
• Sponsor: Usona Institute
• Information provided by (Responsible Party): Usona Institute

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pharmacokinetics; Safety; Tolerability	Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt; Drug: Placebo	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment

Intervention 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 (Participant, Care Provider, Investigator)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: December 27, 2022
• Estimated Primary Completion Date: September 7, 2023
• Estimated Study Completion Date: March 11, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1 - 0.5 mg single-dose; 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; 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.; Other Names: 5-MeO-DMT succinate salt; 5-MeO-DMT; Drug: Placebo; 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.; Other Name: 0.9% sodium chloride solution (USP)
Experimental: Cohort 2 - 2.5 mg single-dose; 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; 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.; Other Names: 5-MeO-DMT succinate salt; 5-MeO-DMT; Drug: Placebo; 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.; Other Name: 0.9% sodium chloride solution (USP)
Experimental: Cohort 3 - 4.5 mg single-dose; 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; 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.; Other Names: 5-MeO-DMT succinate salt; 5-MeO-DMT; Drug: Placebo; 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.; Other Name: 0.9% sodium chloride solution (USP)
Experimental: Cohort 4 - 7 mg single-dose; 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; 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.; Other Names: 5-MeO-DMT succinate salt; 5-MeO-DMT; Drug: Placebo; 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.; Other Name: 0.9% sodium chloride solution (USP)
Experimental: Cohort 5 - 10 mg single-dose; 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; 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.; Other Names: 5-MeO-DMT succinate salt; 5-MeO-DMT; Drug: Placebo; 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.; Other Name: 0.9% sodium chloride solution (USP)
Experimental: Cohort 6 - 16 mg single-dose; A single 5-MeO-DMT 16 mg or placebo dose administered intramuscularly (randomized as 5 active and 1 placebo subject).	Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt; 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.; Other Names: 5-MeO-DMT succinate salt; 5-MeO-DMT; Drug: Placebo; 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.; Other Name: 0.9% sodium chloride solution (USP)
Experimental: Cohort 7 - multiple-dose, 3 hour interval; 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; 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.; Other Names: 5-MeO-DMT succinate salt; 5-MeO-DMT; Drug: Placebo; 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.; Other Name: 0.9% sodium chloride solution (USP)
Experimental: Cohort 8 - multiple-dose, 3 hour interval; 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; 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.; Other Names: 5-MeO-DMT succinate salt; 5-MeO-DMT; Drug: Placebo; 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.; Other Name: 0.9% sodium chloride solution (USP)
Experimental: Cohort 9 - multiple-dose, 3 hour interval; Administration of up to two 5-MeO-DMT (4.5 mg followed by 11.5 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; 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.; Other Names: 5-MeO-DMT succinate salt; 5-MeO-DMT; Drug: Placebo; 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.; Other Name: 0.9% sodium chloride solution (USP)

Outcome Measures

Primary Outcome Measures :

1. Number of participants with Treatment Emergent Adverse Events as coded by MedDRA and assessed by CTCAE v4.0 [ Time Frame: Up to 30 Days ]
   Number of participants with TEAEs following administration of 5-MeO-DMT.

Secondary Outcome Measures :

1. Plasma pharmacokinetic parameters of 5-MeO-DMT and bufotenine following a single-dose and multiple-doses of 5-MeO-DMT [ Time Frame: Up to 24 hours ]
   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.
2. Urine pharmacokinetic parameters of 5-MeO-DMT and bufotenine following a single-dose and multiple-doses of 5-MeO-DMT [ Time Frame: Up to 24 hours ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Contacts

Contact: Theraysa Gapasin; 608-210-5889; ClinicalTrials@usonainstitute.org

Locations

United States, Kansas

Altasciences Clinical Kansas, Inc; Recruiting

Overland Park, Kansas, United States, 66212

Contact: Recruitment Manager 913-696-1601 volunteersinfo@altasciences.com

Sponsors and Collaborators

Usona Institute

More Information

Publications:

Reckweg J, Mason NL, van Leeuwen C, Toennes SW, Terwey TH, Ramaekers JG. A Phase 1, Dose-Ranging Study to Assess Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N, N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers. Front Pharmacol. 2021 Nov 25;12:760671. doi: 10.3389/fphar.2021.760671. eCollection 2021.

Shen HW, Jiang XL, Winter JC, Yu AM. Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Curr Drug Metab. 2010 Oct;11(8):659-66. doi: 10.2174/138920010794233495.

Barsuglia J, Davis AK, Palmer R, Lancelotta R, Windham-Herman AM, Peterson K, Polanco M, Grant R, Griffiths RR. Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study. Front Psychol. 2018 Dec 6;9:2459. doi: 10.3389/fpsyg.2018.02459. eCollection 2018.

Davis AK, Barsuglia JP, Lancelotta R, Grant RM, Renn E. The epidemiology of 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption. J Psychopharmacol. 2018 Jul;32(7):779-792. doi: 10.1177/0269881118769063. Epub 2018 Apr 30.

Ermakova AO, Dunbar F, Rucker J, Johnson MW. A narrative synthesis of research with 5-MeO-DMT. J Psychopharmacol. 2022 Mar;36(3):273-294. doi: 10.1177/02698811211050543. Epub 2021 Oct 19.

Uthaug MV, Lancelotta R, van Oorsouw K, Kuypers KPC, Mason N, Rak J, Sulakova A, Jurok R, Maryska M, Kuchar M, Palenicek T, Riba J, Ramaekers JG. A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology (Berl). 2019 Sep;236(9):2653-2666. doi: 10.1007/s00213-019-05236-w. Epub 2019 Apr 13.

Sherwood AM, Claveau R, Lancelotta R, Kaylo KW, Lenoch K. Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use. ACS Omega. 2020 Dec 2;5(49):32067-32075. doi: 10.1021/acsomega.0c05099. eCollection 2020 Dec 15.

• Responsible Party: Usona Institute
• ClinicalTrials.gov Identifier: NCT05698095
• Other Study ID Numbers: MEO101
• First Posted: January 26, 2023
• Last Update Posted: January 26, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Usona Institute:

5-MeO-DMT; Psychedelics; Safety; Pharmacokinetics; First-in-human; 5-methoxy-N,N-dimethyltryptamine

Additional relevant MeSH terms:

N,N-Dimethyltryptamine; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Receptor Agonists