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

NCT03638869 | Completed Phase 1

• 1 other identifier: REL-1017-112
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Neuropathic Pain

Outcome Measures

Primary Outcomes (1)

• Adverse Events (AEs)

  Spontaneously reported and observed AEs were recorded throughout the study, and AEs were elicited using a non-leading question at designated time points. Regardless of seriousness, intensity, or presumed relationship to study drug, all AEs were recorded in the source documentation from the time of first contact with the subject (e.g., screening) until the end of the follow-up period of the study. AEs that occurred after medical screening and prior to administration of the first dose of study drug were recorded in the source documentation as baseline signs and symptoms.

  Change from pre-dose, Days 1 through 13, and Days 14, 16±1, and 18±1

Secondary Outcomes (1)

• Plasma levels

  Days 1 through 13, and Days 14, 16±1, and 18±1

Other Outcomes (3)

• Clinical Opiate Withdrawal Scale (COWS)

  Days 11 through 13

• Bond-Lader visual analog scale (VAS) assessment

  Pre-dose and 3 hours post-dose on Day 1 to Day 10 and 72 hours post last dose

• Pupillometry

  Pre-dose and 2, 4, 6, and 8 hours post-dose from Day 2 to Day 9, and from Day 10 to Day 13

Study Arms (4)

Arm 1

PLACEBO COMPARATOR

100 mL Ocean Spray® Diet Cranberry Juice

Drug: Placebo

Arm 2

EXPERIMENTAL

REL-1017 25 mg in 100 mL of Ocean Spray® Diet Cranberry Juice

Drug: REL-1017

Arm 3

EXPERIMENTAL

REL-1017 50 mg in 100 mL of Ocean Spray® Diet Cranberry Juice

Drug: REL-1017

Arm 4

EXPERIMENTAL

REL-1017 75 mg in 100 mL of Ocean Spray® Diet Cranberry Juice

Drug: REL-1017

Interventions

REL-1017 DRUG

The investigational product, REL-1017 is prepared as a solution with Ocean Spray® Diet Cranberry Juice on site to obtain a final volume of 100 mL for dosing. The study drug will be administered as a solution of 25 mg, 50 or 75 mg REL-1017 for 10 days, based on randomization prepared in Ocean Spray® Diet Cranberry Juice with a final volume of 100 mL.

Also known as: (d-Methadone)

Arm 2; Arm 3; Arm 4

Placebo DRUG

Arm 1

Eligibility Criteria

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

You may qualify if:

• healthy male or female subjects, 18 to 55 years of age, inclusive
• body mass index (BMI) within the range of 18.0 to 30.0 kg/m2, inclusive, and a minimum weight of 50.0 kg
• non-smoker for at least 3 months and tested negative on a breath carbon monoxide (CO) test
• 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
• 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
• female subjects of non-childbearing potential must have met the criteria defined in the clinical protocol
• able to speak, read, and understand English sufficiently to allow completion of all study assessments
• must have understood and provided written informed consent, prior to the initiation of any protocol-specific procedures

You may not qualify if:

• 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
• subject-reported family history of substance abuse in an immediate family member (i.e., parent, sibling, or child)
• 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
• chronic use of prescribed opioids (i.e., \>120 days in a 6-month period) or any recreational use of opioids
• 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
• history or family history of sudden unexplained death or long QT syndrome
• QT interval corrected using Fridericia's formula (QTcF) \>450 ms in females or \>430 ms in males
• history of hypotension
• 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)
• history of status asthmaticus, chronic pulmonary disease, or severe allergic reaction (including anaphylaxis) to any substance
• use of an opioid within the 6 months prior to screening
• use of a prohibited medication
• positive urine drug screen
• positive breath alcohol test; subjects with a positive result may have been rescheduled at the investigator's discretion
• female subjects who were currently pregnant (had a positive pregnancy test)

Sponsors & Collaborators

• Relmada Therapeutics, Inc.: lead

MeSH Terms

Conditions

Neuralgia

Interventions

D-methadone

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2018
• First Posted: August 20, 2018
• Study Start: August 31, 2015
• Primary Completion: November 16, 2015
• Study Completion: November 16, 2015
• Last Updated: August 20, 2018

Record last verified: 2018-08