A Randomized Study Investigating Oral Desmetramadol Dose Proportionality and Food Effect In Normal Human Subjects

NCT04683926 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: Omni-Pain-103R44DA046316
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to investigate in healthy human subjects how much desmetramadol (Omnitram) gets in the blood after different oral doses are taken with or without food.

Conditions

Pain

Keywords

Pharmacokinetics; Food effect

Outcome Measures

Primary Outcomes (2)

• (-/+)-M1, AUC(0-32) and AUC(Inf)

  The AUC(0-32) and AUC(inf) of (-/+)-M1 after each treatment (i.e., 10, 20 and 30 mg desmetramadol fasted, and 30 mg desmetramadol fed)

  Pre-dose (0 h), and post-dose 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 ,3.5, 4, 6, 8, 12, 16, 24, and 32 h.

• (-/+)-M1, Cmax

  The Cmax of (-/+)-M1 after each treatment (i.e., 10, 20 and 30 mg desmetramadol fasted, and 30 mg desmetramadol fed)

  Pre-dose (0 h), and post-dose 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 ,3.5, 4, 6, 8, 12, 16, 24, and 32 h.

Secondary Outcomes (1)

• Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment.

  Participant report adverse events throughout study enrolment; investigators observe adverse events during all 11 days of inpatient treatment; laboratory safety labs are obtained on Day 11 (the final study day).

Study Arms (4)

Desmetramadol 10 mg, fasted

EXPERIMENTAL

While fasting a single oral dose of 10 mg desmetramadol under.

Drug: Desmetramadol

Desmetramadol 20 mg, fasted

EXPERIMENTAL

While fasting a single oral dose of 20 mg desmetramadol.

Drug: Desmetramadol

Desmetramadol 30 mg , fasted

EXPERIMENTAL

While fasting a single oral dose of 30 mg desmetramadol.

Drug: Desmetramadol

Desmetramadol 30 mg , fed

EXPERIMENTAL

After feeding a single oral dose of 30 mg desmetramadol.

Drug: Desmetramadol

Interventions

Desmetramadol DRUG

Analgesic

Also known as: Omnitram

Desmetramadol 10 mg, fasted; Desmetramadol 20 mg, fasted; Desmetramadol 30 mg , fasted; Desmetramadol 30 mg , fed

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males and females with vital signs as follows at screening: systolic blood pressure \> 90 mm Hg and \< 140 mm Hg; diastolic blood pressure \> 40 mm Hg and \< 90 mm Hg; pulse 40 to 99 beats per minute; respiratory rate 12 to 24 breathes per minute.
• Age 19 to 55 years.
• Able and willing to give informed consent
• Able to comply with all study procedures.
• If female, must not be of childbearing potential or must agree to use one or more of the following forms of contraception from screening, throughout the study and for 30 days following study drug administration: hormonal (e.g., oral, transdermal, intravaginal, implant or injection for 3 months); double barrier (e.g., condom or diaphragm with spermicide); intrauterine device (IUD) or system (IUS) (for 3 months); vasectomized partner (6 months minimum); or abstinence.
• Screening laboratory results must be within normal range per clinical research unit: serum sodium, potassium, calcium, BUN, creatinine, ALT, AST, total bilirubin, alkaline phosphatase, glucose (random), albumin, total protein, WBC and differential, hemoglobin, and platelets. In addition PT and PTT must be \< 1.2 ULN.
• Electrocardiogram (ECG) without clinically significant abnormalities.
• Urinalysis demonstrating \< +1 glucose, and +1 protein.
• If female, must have a negative pregnancy test at screening
• Negative urine test for substances of abuse, including opiates, per clinical pharmacology unit standards at screening and clinic check-in.
• Negative serology tests for HIV, hepatitis B surface antigen, and hepatitis C virus antibody.
• Weight \> 50 Kg and a body mass index (BMI) of 18.0 to 32.0 kg/m (inclusive).
• Non-smoker of tobacco for a minimum of the past 3 months, and negative urine continine test.

You may not qualify if:

• Oral temperature \> 38°C or current illness.
• History of seizures, epilepsy, or recognized increase risk of seizure (e.g., head trauma, metabolic disorders, alcohol or drug withdrawal).
• History of cirrhosis or laboratory evidence of liver disease.
• Having undergone gall bladder removal.
• Use of alcohol within 24 hours of day -1 until the end of the study; and grapefruit, grapefruit-related citrus fruits (e.g., Seville oranges, pomelos), or grapefruit juice or grapefruit-related juices within 7 days of study drug administration and until the end of the study.
• History of previous anaphylaxis, severe allergic reaction to tramadol, codeine, or other opioid drugs.
• Any other unstable acute or chronic disease that could interfere with the evaluation of the safety of the study drug as determined by the principal Investigator in dialogue with the Sponsor Medical Monitor.
• Females must not be currently pregnant or breast feeding.
• Unlikely to comply with the study protocol.
• Known or suspected alcohol or drug abuse within the past 6 months.
• Received another investigational agent within 4 weeks of Day -1, or within five half-lives of Day -1, whichever is longer; or receiving any other investigational agent during this study.
• Any concurrent disease or condition that in the opinion of the investigator impairs the subject's ability to complete the trial. Psychological, familial, sociological, geographical or medical conditions which, in the Investigator's opinion, could compromise compliance with the objectives and procedures of this protocol, or obscure interpretation of the trial data.

Sponsors & Collaborators

• Syntrix Biosystems, Inc.: lead
• Celerion: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Celerion

Lincoln, Nebraska, 68502, United States

Location

Related Publications (1)

• Zebala JA, Searle SL, Webster LR, Johnson MS, Schuler AD, Maeda DY, Kahn SJ. Desmetramadol Has the Safety and Analgesic Profile of Tramadol Without Its Metabolic Liabilities: Consecutive Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Trials. J Pain. 2019 Oct;20(10):1218-1235. doi: 10.1016/j.jpain.2019.04.005. Epub 2019 Apr 18.

  PMID: 31005596 BACKGROUND

MeSH Terms

Conditions

Pain

Interventions

O-demethyltramadol

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Aaron Schuler
• Organization: Syntrix Pharmaceuticals

aschuler@syntrixbio.com

253-833-8009

Study Officials

• Robert Schwab, MD

  Celerion

  PRINCIPAL INVESTIGATOR

• Stuart Kahn, MD

  Syntrix Biosystems

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Model Details: An open-label, randomized, balanced, single-dose, four-treatment, four-period, four-sequence (using a Williams' square design) cross-over study.

Study Record Dates

• First Submitted: December 21, 2020
• First Posted: December 24, 2020
• Study Start: January 8, 2021
• Primary Completion: January 18, 2021
• Study Completion: January 18, 2021
• Last Updated: April 4, 2023
• Results First Posted: April 4, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)