Healthy
Conditions
Keywords
Healthy, Pain, Tramadol hydrochloride, Tramadol HCl, Analgesic, QT prolongation, RWJ-26898-002
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.
Interventions
DRUGTramadol HCl, 50 mg
50-mg overencapsulated tablet for oral administration
DRUGPlacebo
Size-matching capsules containing an appropriate inactive excipient
Sponsors
Bausch Health Americas, Inc.
Cipher Pharmaceuticals Inc.
Janssen Scientific Affairs, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
United States
Outcome results
None listed