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

NCT05698095 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MEO101
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetics; Safety; Tolerability

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Plasma pharmacokinetic parameters of 5-MeO-DMT and bufotenine following a single-dose and multiple-doses of 5-MeO-DMT

  Up to 24 hours

• Urine pharmacokinetic parameters of 5-MeO-DMT and bufotenine following a single-dose and multiple-doses of 5-MeO-DMT

  Up to 24 hours

Study Arms (9)

Cohort 1 - 0.5 mg single-dose

EXPERIMENTAL

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; Drug: Placebo

Cohort 2 - 2.5 mg single-dose

EXPERIMENTAL

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; Drug: Placebo

Cohort 3 - 4.5 mg single-dose

EXPERIMENTAL

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; Drug: Placebo

Cohort 4 - 7 mg single-dose

EXPERIMENTAL

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; Drug: Placebo

Cohort 5 - 10 mg single-dose

EXPERIMENTAL

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; Drug: Placebo

Cohort 6 - 13 mg single-dose

EXPERIMENTAL

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; Drug: Placebo

Cohort 7 - multiple-dose, 3 hour interval

EXPERIMENTAL

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; Drug: Placebo

Cohort 8 - multiple-dose, 3 hour interval

EXPERIMENTAL

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; Drug: Placebo

Cohort 9 - multiple-dose, 3 hour interval

EXPERIMENTAL

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; Drug: Placebo

Interventions

5-methoxy-N,N-dimethyltryptamine succinate salt DRUG

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.

Also known as: 5-MeO-DMT succinate salt, 5-MeO-DMT

Cohort 1 - 0.5 mg single-dose; Cohort 2 - 2.5 mg single-dose; Cohort 3 - 4.5 mg single-dose; Cohort 4 - 7 mg single-dose; Cohort 5 - 10 mg single-dose; Cohort 6 - 13 mg single-dose; Cohort 7 - multiple-dose, 3 hour interval; Cohort 8 - multiple-dose, 3 hour interval; Cohort 9 - multiple-dose, 3 hour interval

Placebo DRUG

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.

Also known as: 0.9% sodium chloride solution (USP)

Cohort 1 - 0.5 mg single-dose; Cohort 2 - 2.5 mg single-dose; Cohort 3 - 4.5 mg single-dose; Cohort 4 - 7 mg single-dose; Cohort 5 - 10 mg single-dose; Cohort 6 - 13 mg single-dose; Cohort 7 - multiple-dose, 3 hour interval; Cohort 8 - multiple-dose, 3 hour interval; Cohort 9 - multiple-dose, 3 hour interval

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Usona Institute: lead

Study Sites (1)

Altasciences Clinical Kansas, Inc

Overland Park, Kansas, 66212, United States

Location

Related Publications (7)

• 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.

  PMID: 34912222 BACKGROUND

• 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.

  PMID: 20942780 BACKGROUND

• 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.

  PMID: 30574112 BACKGROUND

• 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.

  PMID: 29708042 BACKGROUND

• 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.

  PMID: 34666554 BACKGROUND

• 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.

  PMID: 30982127 BACKGROUND

• 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.

  PMID: 33344861 BACKGROUND

MeSH Terms

Interventions

Methoxydimethyltryptamines; Sodium Chloride

Intervention Hierarchy (Ancestors)

N,N-Dimethyltryptamine; Tryptamines; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Bufotenin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Serotonin; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: January 5, 2023
• First Posted: January 26, 2023
• Study Start: December 27, 2022
• Primary Completion: September 7, 2023
• Study Completion: September 7, 2023
• Last Updated: November 30, 2023

Record last verified: 2023-11

Locations

US (1)