A Dose Ranging Escalation Study of Tramadol Hydrochloride in Healthy Volunteers

Sponsor

Janssen Scientific Affairs, LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT01947920

Collaborator

Bausch Health Americas, Inc. (Industry), Cipher Pharmaceuticals Inc. (Industry)

Enrollment

Location

Arms

Duration (Months)

9.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Tramadol HCl, 50 mg Drug: Placebo	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2013

Actual Primary Completion Date :

Nov 1, 2013

Actual Study Completion Date :

Nov 1, 2013

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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