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).

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.

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