A Dose Ranging Escalation Study of Tramadol Hydrochloride in Healthy Volunteers
- Registration Number
- NCT01947920
- Lead Sponsor
- Janssen Scientific Affairs, LLC
- 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).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2: Tramadol HCl 400 mg daily or placebo Tramadol HCl, 50 mg 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. 3: Tramadol HCl 600 mg daily or placebo 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. 1: Tramadol HCl 200 mg daily or placebo Tramadol HCl, 50 mg 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. 1: Tramadol HCl 200 mg daily or placebo 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. 2: Tramadol HCl 400 mg daily or placebo 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. 3: Tramadol HCl 600 mg daily or placebo Tramadol HCl, 50 mg 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
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.
Incidence and type of adverse events Baseline, till the end of study