A Dose Ranging Escalation Study of Tramadol Hydrochloride in Healthy Volunteers

A Randomized, Double-Blind, Placebo-Controlled Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics Following Multiple Ascending Doses of Tramadol Hydrochloride in Healthy Male and Female Subjects

The purpose of this study is to determine the safety and tolerability profile of tramadol hydrochloride (HCl) given as oral doses every 6 hours, within the range of dosages supported by currently available toxicology and clinical data (200 mg to 600 mg per day).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tramadol HCl, 50 mg; Drug: Placebo

Detailed Description

This is a randomized (study drug assigned by chance), sequential-cohort (time lagged), double-blind (neither the participant or the study doctor will know the name of the assigned treatment), parallel-group, placebo-controlled, 3-arm (participants will be assigned to 1 of 3 treatment groups), single-center, Phase 1 study of multiple ascending doses of tramadol HCl in healthy adult volunteers. Thirty participants (15 men and 15 women) will be sequentially assigned to 1 of 3 treatment groups of 10 subjects each (5 men and 5 women). Participants in each treatment group will receive a total of 9 oral doses (one every 6 hours) of tramadol HCl or placebo, in the ratio of 4:1. The study includes a screening phase and a double-blind treatment phase. The treatment phase will consist of 3 treatment periods separated by a 5-day safety review period before the next ascending dose of study drug is administered to the next group. Participants in each group will be confined to the study center for a total of 5 days, the total duration of each subject's participation will be up to 33 days, including the screening phase. The total duration of the study (completion of all 3 treatment cohorts) will be up-to-approximately 2 months.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• body mass index between 18 and 30 kg/m², inclusive
• body weight not less than 50 kg
• have a normal electroencephalogram under basic and stimulated conditions
• have a 12-lead ECG that is consistent with normal cardiac conduction and function
• have not used any tobacco products (eg, cigarettes, cigars, chewing tobacco, gum, or patch) for at least 6 months before first study drug administration

Exclusion Criteria:

• any personal or family history of epileptic seizures or convulsions
• have suffered from head trauma with loss of consciousness -have suffered from central nervous system infection
• have suffered from loss of consciousness of unknown origin
• drowning or sudden infant death syndrome in a first degree relative

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1: Tramadol HCl 200 mg daily or placebo; Participants will receive one capsule of Tramadol hydrochloride (HCl) every 6 hours. Participants assigned to placebo will receive matching placebo capsules. A total of 9 doses will be administered.	Drug: Tramadol HCl, 50 mg; 50-mg overencapsulated tablet for oral administration; Drug: Placebo; Size-matching capsules containing an appropriate inactive excipient
Experimental: 2: Tramadol HCl 400 mg daily or placebo; Participants will recieve two capsules of Tramadol HCl every 6 hours. Participants assigned to placebo will receive matching placebo capsules. A total of 9 doses will be administered.	Drug: Tramadol HCl, 50 mg; 50-mg overencapsulated tablet for oral administration; Drug: Placebo; Size-matching capsules containing an appropriate inactive excipient
Experimental: 3: Tramadol HCl 600 mg daily or placebo; Participants will receive three capsules of Tramadol HCl every 6 hours. Participants assigned to placebo will receive matching placebo capsules. A total of 9 doses will be administered.	Drug: Tramadol HCl, 50 mg; 50-mg overencapsulated tablet for oral administration; Drug: Placebo; Size-matching capsules containing an appropriate inactive excipient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in vital signs and other parameters as a measure of safety and tolerability of tramadol	Changes in clinical laboratory results, vital signs, psycopharmacologic status (Richmond Agitation-Sedation Scale (RASS), and physical examination.	Baseline, Days 1 through 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in time-matched electrocardiogram (ECG) measurements	ECG will detect abnormal changes from baseline in cardiac depolarization/repolarization.	Baseline, Day 1, Day 3 and Day 4
Change from baseline in pharmacokinetic parameters of tramadol and M1 metabolite	Determination of concentrations of tramadol and M1 metabolite pharmacokinetic parameters in venous plasma.	Baseline, up to 72 hours after the 1st dose
Incidence and type of adverse events		Baseline, till the end of study

Collaborators and Investigators

• Sponsor: Janssen Scientific Affairs, LLC
• Collaborators: Bausch Health Americas, Inc.; Cipher Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: August 13, 2013
• First Submitted That Met QC Criteria: September 18, 2013
• First Posted (Estimate): September 23, 2013

Study Record Updates

• Last Update Posted (Estimate): December 16, 2014
• Last Update Submitted That Met QC Criteria: December 15, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Pain; Healthy; Analgesic; QT prolongation; Tramadol hydrochloride; Tramadol HCl; RWJ-26898-002
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Tramadol
• Other Study ID Numbers: CR102458; TRAMPAI1002 (Other Identifier: Janssen Scientific Affairs, LLC); V01-TRAA-501 (Other Identifier: Valeant Pharmaceuticals International Inc); 2013-01-00 (Other Identifier: Cipher Pharmaceuticals Inc)