Omnitram Pharmacokinetic and Analgesic Study Following CY2D6 Inhibition With Paroxetine In Healthy Volunteers

NCT03312777 | Completed Phase 1 FDA Drug

• 1 other identifier: Omni-Pain-102
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the analgesic effect of Omnitram and tramadol during concurrent administration of paroxetine. Paroxetine administration is expected to diminish the analgesic effect of tramadol, but not Omnitram. Each participant will receive paroxetine before and during treatment with Omnitram, tramadol, and placebo.

Conditions

Pain

Keywords

analgesia, Cytochrome P450 2D6

Outcome Measures

Primary Outcomes (1)

• Cold Pressor Test - Cold Water Induced-Pain

  The participant immerses a hand in cold water for a maximum of 3 minutes and reports the pain they experience using a "0 (no pain) to 10 (worst pain)" scale. Immersion of hand in ice cold water

  The test is performed on Day 3, shortly after the ninth (final) dose of study drug.

Secondary Outcomes (2)

• Adverse Events

  Participant report adverse events throughout study enrolment; investigators observe adverse events during all three 3 day inpatient treatment segments; laboratory safety labs are obtained on Day 3 of treatment segment 3 (the final treatment segment).

• Steady State Pharmacokinetics

  8 hours

Study Arms (3)

Omnitram

EXPERIMENTAL

Oral Omnitram 20 mg (overencapsulated 10 mg tablets) administered every 6 hours for nine doses, coadministered with paroxetine.

Drug: Omnitram

Tramadol

ACTIVE COMPARATOR

Oral tramadol 50 mg (overencapsulated 50 mg tablet) administered every 6 hours for nine doses, coadministered with paroxetine.

Drug: Tramadol

Placebo

PLACEBO COMPARATOR

Oral placebo (overencapsulated microcrystalline) administered every 6 hours for nine doses, coadministered with paroxetine.

Drug: Placebo

Interventions

Omnitram DRUG

Omnitram tablets overencapsulated

Omnitram

Tramadol DRUG

Tramadol tablet overencapsulated

Tramadol

Placebo DRUG

Microcrystalline powder overencapsulated

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males and females with normal vital signs: systolic blood pressure \> 90 mm Hg and \< 140 mm Hg; diastolic blood pressure \> 45 mm Hg and \< 90 mm Hg; pulse 40 to 100 beats per minute; respiratory rate 10 to 20 breathes per minute.
• Between the ages of 18 and 50 years of age.
• 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 during screening and for 30 days following study drug administration: hormonal (e.g., oral, transdermal, intravaginal, implant or injection); double barrier (i.e., condom, diaphragm with spermicide); intrauterine device (IUD) or system (IUS); vasectomized partner (6 months minimum); abstinence; or bilateral tubal ligation.
• Have adequate hematologic function as evidenced by the following screening results:
• WBC \>3,500/mm3 and \< 12,000/mm3 Platelet Count \> 150,000/mm3 and \< 540,000/mm3 Hemoglobin \> 12.0 gm/dL and \< 20.5 gm/dL
• Have adequate liver function as evidenced by the following screening results:
• AST (SGOT) ≤ 60 IU/L ALT (SGPT) men ≤ 83 IU/L women \< 60 IU/L Alkaline Phosphatase ≤ 200 IU/L Total Bilirubin ≤ 1.2 mg/dL PT and PTT \< 1.2 ULN
• Electrocardiogram (ECG) without clinically significant findings as determined by the PI.
• Have adequate renal function as evidenced by the following screening result:
• Glomerular filtration rate (GFR) calculated by Cockcroft-Gault formula \>60 ml/min.
• Urinalysis demonstrating \< +1 glucose, +1 ketones, and +1 protein.
• Negative pregnancy test within 1 week of study day 1 (women of childbearing potential only).
• Negative urine test for substances of abuse, including opiates, per CRU standards.

You may not qualify if:

• Oral temperature \> 38°C or history of 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.
• 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, or other medication, within 7 days of study drug administration and until the end of the study.
• History of previous anaphylaxis, severe allergic reaction to paroxetine, tramadol, codeine, or other opioid drugs.
• Use of MAO Inhibitors (including linezolid), Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and prescription or over-the counter (OTC) medications known to induce or inhibit drug metabolism, including CYP2D6, and other drugs that may affect the serotonergic neurotransmitter systems including, but not limited to, triptans, dextromethorphan, tricyclic antidepressants, bupropion, lithium, tramadol, dietary supplements such as tryptophan and St. John's Wort, and antipsychotics or other dopamine antagonists. These restrictions are to be maintained from 14 days before study day -1, until the subject completes the study.
• 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.
• 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 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
• PRA Health Sciences: collaborator
• DF/Net Rearch: collaborator
• ITT Research Institute: collaborator

Study Sites (1)

PRA Health Sciences

Salt Lake City, Utah, 84124, 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 DERIVED

MeSH Terms

Conditions

Pain; Agnosia

Interventions

Tramadol

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Dimethylamines; Methylamines; Amines; Lipids

Study Officials

• Shawn L Searle, MD

  PRA Health Sciences

  PRINCIPAL INVESTIGATOR

• Stuart Kahn, MD

  Syntrix Biosystems

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Overencapsulation
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2017
• First Posted: October 18, 2017
• Study Start: October 31, 2017
• Primary Completion: December 15, 2017
• Study Completion: December 22, 2017
• Last Updated: December 28, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)