Evaluation of the Safety and Pharmacokinetics of MSI-195 to a Commercial S-Adenosylmethionine

NCT04623034 | Completed Phase 1 FDA Drug

• 1 other identifier: MSI-CP.001.02
• Study Type: interventional
• Target: 34
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study was a pharmacokinetic and safety evaluation of the S-adenosylmethionine formulation MSI-195, and a commercial comparator. The study was broken into two stages. The first stage was an exploratory single ascending dose design of MSI-195 in 8 healthy normal male volunteers. The second stage was a single dose evaluation, targeting 26 male and female volunteers at set doses of MSI-195 and commercial comparator in a cross-over design followed by a food effect study on MSI-195. Plasma samples were collected and assayed for S-adenosylmethionine. Pharmacokinetic parameters were calculated using that data.

Conditions

Major Depressive Disorder

Keywords

depression

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of treatment-related adverse events (safety and tolerability) as measured by vital signs, ECG, laboratory tests, neurological function tests, and the occurance of adverse events

  Incidence and severity of treatment-related adverse events determined by changes from screening (baseline) of findings from physical examination, vital signs, ECG, laboratory tests, neurological function tests, and the occurance of adverse events.

  for 24 hours after dosing

• Pharmacokinetics was evaluated by measuring the systemic plasma concentration of ademetionine

  plasma concentrations of ademetionine were measured as a function of time using a validated bioanalytical assay

  for 24 hours after dosing

Study Arms (6)

400 mg MSI-195 - SAD

EXPERIMENTAL

400 mg MSI-195 (within Stage 1, single ascending dose)

Drug: Ademetionine

800 mg MSI-195 - SAD

EXPERIMENTAL

800 mg MSI-195 (within Stage 1, single ascending dose)

Drug: Ademetionine

1600 mg MSI-195 -SAD

EXPERIMENTAL

1600 mg MSI-195 (within Stage 1, single ascending dose)

Drug: Ademetionine

800 mg MSI-195 - fasted

EXPERIMENTAL

800 mg MSI-195 fed (within Stage 2, cross-over comparison)

Drug: Ademetionine

1600 mg SAM-e Complete TM - fasted

EXPERIMENTAL

1600 mg SAM-e Complete (within Stage 2, cross-over comparison)

Drug: Ademetionine

800 mg MSI-195 - fed

EXPERIMENTAL

800 mg MSI-195- fed (within Stage 2, fed arm)

Drug: Ademetionine

Interventions

Ademetionine DRUG

1600 mg MSI-195 -SAD; 1600 mg SAM-e Complete TM - fasted; 400 mg MSI-195 - SAD; 800 mg MSI-195 - SAD; 800 mg MSI-195 - fasted; 800 mg MSI-195 - fed

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Volunteers meeting all of the following criteria will be considered for enrollment in the study:
• Availability for the entire study period
• Motivated volunteer and absence of intellectual problems likely to limit the validity of consent to participate in the study or the compliance with protocol requirements; ability to cooperate adequately; ability to understand and observe the instructions of the physician or designee
• Male or female volunteer (Male only for Stage 1 - Cohort 1)
• A female volunteer must meet one of the following criteria:
• Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens throughout her entire participation in the study. An acceptable method of contraception includes one of the following:
• Abstinence from heterosexual intercourse
• Systemic contraceptives (birth control pills, injectable/implantable /insertable hormonal birth control products, transdermal patch)
• Intrauterine device
• Condom with spermicide or
• Participant is of non-childbearing potential, defined as a female who had had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses)
• Volunteer aged of at least 21 years but not older than 55 years
• Volunteer with a body mass index (BMI) greater than or equal to 18.50 and below 30.00 kg/m2
• Non- or ex smokers; an ex-smoker being defined as someone who completely stopped smoking for at least 6 months before day 1 of this study.
• Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance

You may not qualify if:

• Volunteers presenting any of the following will not be included in the study:
• Females who are pregnant or are lactating
• History of significant hypersensitivity to S-Adenosylmethionine or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
• Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects
• History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability
• Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
• Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
• Presence of out-of-range cardiac interval (PR \< 110 msec, PR \> 220 msec, QRS \< 60 msec, QRS \>119 msec, QTc \> 450 msec for males and \> 460 msec for females) on the screening ECG or other clinically significant ECG abnormalities
• Presence or history of bipolar disorder
• Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
• Any clinically significant illness in the previous 28 days before day 1 of this study
• Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort), in the previous 28 days before day 1 of this study
• Any history of tuberculosis and/or prophylaxis for tuberculosis
• Positive urine screening of alcohol and/or drugs of abuse
• Positive results to HIV Ag/Ac Combo, HBsAg (B) (hepatitis B) or anti-HCV (C) tests

Sponsors & Collaborators

• MSI Methylation Sciences, Inc.: lead
• Algorithme Pharma Inc: collaborator

Related Publications (1)

• Cameron BR, Ferreira L, MacDonald ID. Pharmacokinetic study of a novel oral formulation of S-adenosylmethionine (MSI-195) in healthy subjects: dose escalation, food effect and comparison to a commercial nutritional supplement product. BMC Pharmacol Toxicol. 2020 Dec 14;21(1):88. doi: 10.1186/s40360-020-00466-7.

  PMID: 33317621 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

S-Adenosylmethionine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Methionine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Amino Acids; Amino Acids, Peptides, and Proteins; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Eric Sicard, M.D.

  Algorithme Pharma Inc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Stage 1 - single ascending dose, Stage 2 - crossover and food effect study

Study Record Dates

• First Submitted: October 30, 2020
• First Posted: November 10, 2020
• Study Start: April 17, 2013
• Primary Completion: June 8, 2013
• Study Completion: June 8, 2013
• Last Updated: November 10, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share