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

• Status: Completed
• Trial end date: 2013-06-08
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: MSI Methylation Sciences, Inc.
• Collaborator: Algorithme Pharma Inc

Criteria

Inclusion Criteria:

• Volunteers meeting all of the following criteria will be considered for enrollment in the study:

1. Availability for the entire study period

2. 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

3. Male or female volunteer (Male only for Stage 1 - Cohort 1)

4. A female volunteer must meet one of the following criteria:

1. 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

2. 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)

5. Volunteer aged of at least 21 years but not older than 55 years

6. Volunteer with a body mass index (BMI) greater than or equal to 18.50 and below 30.00 kg/m2

7. 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.

8. Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance

9. Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations (hematology, general biochemistry, ECG and urines)

10. Willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer

The informed consent form must be signed by all volunteers, prior to their participation in the study.

Exclusion Criteria:

• Volunteers presenting any of the following will not be included in the study:

1. Females who are pregnant or are lactating

2. 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

3. 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

4. History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability

5. Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease

6. Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases

7. 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

8. Presence or history of bipolar disorder

9. 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)

10. Any clinically significant illness in the previous 28 days before day 1 of this study

11. 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

12. Any history of tuberculosis and/or prophylaxis for tuberculosis

13. Positive urine screening of alcohol and/or drugs of abuse

14. Positive results to HIV Ag/Ac Combo, HBsAg (B) (hepatitis B) or anti-HCV (C) tests

15. Females who are pregnant according to a positive serum pregnancy test

16. Volunteers who took an Investigational Product (in another clinical trial) or donated 50 mL or more of blood in the previous 28 days before day 1 of this study

17. Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before day 1 of this study

No subjects will be allowed to enroll in this study more than once (i.e. if the study is conducted with more than 1 group).