A Double-blind, Placebo-controlled, Randomized, Single Ascending, and Multiple Dose Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral Dose Isomyosamine Capsules in Healthy Adult Subjects.
Journal
Drug research
ISSN: 2194-9387
Titre abrégé: Drug Res (Stuttg)
Pays: Germany
ID NLM: 101602406
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
pubmed:
12
11
2022
medline:
9
2
2023
entrez:
11
11
2022
Statut:
ppublish
Résumé
Aging is tightly linked to chronic disease, frailty, and death. Multi-morbidity, defined as the presence in the same patient of three or more conditions such as neoplastic, cardiovascular, neurodegenerative, metabolic, or autoimmune diseases, becomes more common with age. The study was performed in a double-blind fashion. Subjects within each dose cohort (Cohorts 1, 2, 3, and 4) were randomly assigned to receive Isomyosamine doses (between 150 mg to 600 mg or placebo) or placebo in a 3:1 ratio (6 active: 2 placebo). Isomyosamine single daily doses each of 150 mg, 300 mg, and 450 mg for 3 days and multiple daily doses of 600 mg for 6 days were safe and well tolerated in healthy subjects. In one dose group, there was a decrease in TNF-α levels found in Isomyosamine treated subjects, but no change in the levels in subjects given placebo. The increase in Isomyosamine exposure was proportional to dose across the dose range of 300 mg to 600 mg when administered as a single dose. There was minimal accumulation of Isomyosamine following 5 days of once daily dosing of Isomyosamine 600 mg. Isomyosamine half-life ranged from approximately 15 minutes to 45 minutes across all doses in the single ascending dose and multiple ascending dose portion of the study. Elimination of Isomyosamine included the renal pathway as a minor route. Isomyosamine will continue to be investigated in phase 2 clinical trials for the treatment of sarcopenia/frailty, hashimoto's thyroiditis and rheumatoid arthritis.
Sections du résumé
BACKGROUND
BACKGROUND
Aging is tightly linked to chronic disease, frailty, and death. Multi-morbidity, defined as the presence in the same patient of three or more conditions such as neoplastic, cardiovascular, neurodegenerative, metabolic, or autoimmune diseases, becomes more common with age.
METHODS
METHODS
The study was performed in a double-blind fashion. Subjects within each dose cohort (Cohorts 1, 2, 3, and 4) were randomly assigned to receive Isomyosamine doses (between 150 mg to 600 mg or placebo) or placebo in a 3:1 ratio (6 active: 2 placebo).
RESULTS
RESULTS
Isomyosamine single daily doses each of 150 mg, 300 mg, and 450 mg for 3 days and multiple daily doses of 600 mg for 6 days were safe and well tolerated in healthy subjects. In one dose group, there was a decrease in TNF-α levels found in Isomyosamine treated subjects, but no change in the levels in subjects given placebo. The increase in Isomyosamine exposure was proportional to dose across the dose range of 300 mg to 600 mg when administered as a single dose. There was minimal accumulation of Isomyosamine following 5 days of once daily dosing of Isomyosamine 600 mg. Isomyosamine half-life ranged from approximately 15 minutes to 45 minutes across all doses in the single ascending dose and multiple ascending dose portion of the study. Elimination of Isomyosamine included the renal pathway as a minor route.
CONCLUSION
CONCLUSIONS
Isomyosamine will continue to be investigated in phase 2 clinical trials for the treatment of sarcopenia/frailty, hashimoto's thyroiditis and rheumatoid arthritis.
Identifiants
pubmed: 36368677
doi: 10.1055/a-1962-6834
pmc: PMC9902179
doi:
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
95-104Informations de copyright
The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Déclaration de conflit d'intérêts
Drs. Brager, Chapman, and Kaplin are employees of MyMD Pharmaceuticals, Inc.
Références
Nat Aging. 2021 Jan;1(1):73-86
pubmed: 33796866
J Neuroimmunol. 2020 Feb 15;339:577115
pubmed: 31778849
Biochim Biophys Acta Mol Basis Dis. 2020 Mar 1;1866(3):165612
pubmed: 31816437
Cell Tissue Res. 2017 Mar;367(3):469-480
pubmed: 27743206
J Immunol. 2019 Mar 1;202(5):1350-1362
pubmed: 30674573
BMJ Open. 2015 Feb 03;5(2):e006413
pubmed: 25649210
J Gerontol A Biol Sci Med Sci. 2022 Aug 02;:
pubmed: 35914953