Clinical trial NCT01947920: A Dose Ranging Escalation Study of Tramadol Hydrochloride in Healthy Volunteers
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Pain
Tramadol hydrochloride
Tramadol HCl
Analgesic
QT prolongation
RWJ-26898-002
Lead sponsor: Janssen Scientific Affairs, LLC
Sponsor class: INDUSTRY
Collaborators: name: Bausch Health Americas, Inc.
name: Cipher Pharmaceuticals Inc.
First posted: 2013-09-23
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change from baseline in vital signs and other parameters as a measure of safety and tolerability of tramadol
timeFrame: Baseline, Days 1 through 4
Secondary outcomes:
measure: Change from baseline in time-matched electrocardiogram (ECG) measurements
timeFrame: Baseline, Day 1, Day 3 and Day 4
measure: Change from baseline in pharmacokinetic parameters of tramadol and M1 metabolite
timeFrame: Baseline, up to 72 hours after the 1st dose
measure: Incidence and type of adverse events
timeFrame: Baseline, till the end of study
Other outcomes:
Locations:
city: Overland Park
country: United States
state: Kansas
Study officials:
affiliation: Janssen Scientific Affairs, LLC
name: Janssen Scientific Affairs, LLC Clinical trial
role: STUDY_DIRECTOR
References: