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
Overview
- Phase
- Phase 1
- Intervention
- Tramadol HCl, 50 mg
- Conditions
- Healthy
- Sponsor
- Janssen Scientific Affairs, LLC
- Enrollment
- 30
- Primary Endpoint
- Change from baseline in vital signs and other parameters as a measure of safety and tolerability of tramadol
- Status
- Completed
- Last Updated
- 11 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
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.
Intervention: Tramadol HCl, 50 mg
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.
Intervention: Placebo
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.
Intervention: Tramadol HCl, 50 mg
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.
Intervention: Placebo
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.
Intervention: Tramadol HCl, 50 mg
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Change from baseline in vital signs and other parameters as a measure of safety and tolerability of tramadol
Time Frame: Baseline, Days 1 through 4
Changes in clinical laboratory results, vital signs, psycopharmacologic status (Richmond Agitation-Sedation Scale (RASS), and physical examination.
Secondary Outcomes
- Change from baseline in pharmacokinetic parameters of tramadol and M1 metabolite(Baseline, up to 72 hours after the 1st dose)
- Change from baseline in time-matched electrocardiogram (ECG) measurements(Baseline, Day 1, Day 3 and Day 4)
- Incidence and type of adverse events(Baseline, till the end of study)