Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of REL-1017 (d-Methadone)

• Status: Completed
• Trial end date: 2015-11-16
• Target enrollment: 0
• Participant gender: All

Summary

This study evaluated the safety, tolerance, and pharmacokinetics (PK) of d-methadone in a limited dose range, in multiple administrations in humans.

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

Details

• Lead Sponsor: Relmada Therapeutics, Inc.
• Treatments: D-methadone; Methadone

Criteria

Inclusion Criteria:

1. healthy male or female subjects, 18 to 55 years of age, inclusive

2. body mass index (BMI) within the range of 18.0 to 30.0 kg/m2, inclusive, and a minimum weight of 50.0 kg

3. non-smoker for at least 3 months and tested negative on a breath carbon monoxide (CO) test

4. male subjects of reproductive potential must have been using and willing to continue using medically acceptable contraception from screening and for at least 2 months after the last study drug administration

5. female subjects of childbearing potential must have been using and willing to continue using medically acceptable contraception for at least 1 month prior to screening (at least 3 months for oral, transdermal, vaginal ring contraceptives) and for at least 2 months after last study drug administration

6. female subjects of non-childbearing potential must have met the criteria defined in the clinical protocol

7. able to speak, read, and understand English sufficiently to allow completion of all study assessments

8. must have understood and provided written informed consent, prior to the initiation of any protocol-specific procedures

Exclusion Criteria:

1. self-reported substance or alcohol dependence (excluding nicotine and caffeine) within the past 2 years, and/or subjects who had ever been in a substance or alcohol rehabilitation program to treat their substance or alcohol dependence

2. subject-reported family history of substance abuse in an immediate family member (i.e., parent, sibling, or child)

3. history or presence of clinically significant abnormality as assessed by physical examination, medical history, 12-lead ECG, vital signs, or laboratory values, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results

4. chronic use of prescribed opioids (i.e., >120 days in a 6-month period) or any recreational use of opioids

5. evidence of clinically significant hepatic or renal impairment, including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5× upper limit of normal (ULN) or bilirubin >1× ULN

6. history or family history of sudden unexplained death or long QT syndrome

7. QT interval corrected using Fridericia's formula (QTcF) >450 ms in females or >430 ms in males

8. history of hypotension

9. history or presence of any condition in which an opioid was contraindicated (e.g., significant respiratory depression, acute or severe bronchial asthma or hypercarbia, bronchitis, or had/was suspected of having paralytic ileus)

10. history of status asthmaticus, chronic pulmonary disease, or severe allergic reaction (including anaphylaxis) to any substance

11. use of an opioid within the 6 months prior to screening

12. use of a prohibited medication

13. positive urine drug screen

14. positive breath alcohol test; subjects with a positive result may have been rescheduled at the investigator's discretion

15. female subjects who were currently pregnant (had a positive pregnancy test)

16. history of allergy or hypersensitivity to methadone or related drugs (e.g., opioids)

17. positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)

18. donation or loss of more than 500 mL of whole blood within 30 days prior to first drug administration

19. difficulty with venous access or unsuitable or unwilling to undergo catheter insertion

20. treatment with an investigational drug within 5 times the elimination half-life, if known (e.g., a marketed product) or within 30 days (if the elimination half-life is unknown) prior to first drug administration or was concurrently enrolled in any research judged not to be scientifically or medically compatible with this study

21. an employee of the sponsor or research site personnel directly affiliated with this study or their immediate family member, defined as a spouse, parent, sibling, or child, whether biological or legally adopted

22. a subject who, in the opinion of the investigator or designee, was considered unsuitable or unlikely to comply with the study protocol for any reason