Clinical trial NCT00973232: A Comparative Bioavailability/Food Effect Study of Immediate-Release and Extended-Release Tramadol HCl/Acetaminophen Combination Products Following Single-Dose and Multiple-Dose Administration in Healthy Adult Volunteers
Official title: A Single-Centre, Open-Label, Randomised Study to Compare the Single Dose (Including the Effect of Food) and Multiple Dose Pharmacokinetic Profiles of Acetram Contramid® BID Tablets vs the Immediate-Release Tablet Reference Products Zaldiar® and Ultracet®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Tramadol
Acetaminophen
combination
pharmacokinetics
bioavailability
Zaldiar
Ultracet
fed
fasted
single-dose
multiple-dose
healthy
volunteers
Healthy volunteers
Lead sponsor: Labopharm Inc.
Sponsor class: INDUSTRY
First posted: 2009-09-09
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: The objectives of this two-part study were to compare the single-dose and multiple-dose pharmacokinetics of extended release and immediate-release fixed combination formulations containing tramadol-HCl/acetaminophen and to evaluate the effect of food on the extended-release formulation.

Detailed description: * To compare the single (Part A) and multiple dose (Part B) pharmacokinetic profiles and bioavailability of DDS-06C tablets with the immediate-release tablet reference products Zaldiar® and Ultracet®.
* To assess the effect of food on the pharmacokinetic profile of DDS-06C tablets following administration of a single oral dose.
* To monitor and record all adverse events.

Eligibility criteria: Inclusion Criteria:

* Adult males or females aged 18-55 years inclusive with body mass index (BMI) between 18-30 kg/m2
* Healthy as determined by pre-study medical history, physical examination and 12-lead ECG
* Clinical laboratory tests within the reference ranges or clinically acceptable to the Investigator
* Negative for hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) I and II tests at screening
* Negative for drugs of abuse and alcohol at screening and admission
* Non-smokers for at least 3 months preceding screening
* If female, were not currently pregnant or breast feeding and were using medically acceptable methods of contraception and if male, were themselves and their female partners using medically acceptable methods of contraception
* Able and willing to give written informed consent.

Exclusion Criteria:

* Subjects who did not conform to the above inclusion criteria
* Female subjects who were pregnant, trying to become pregnant, lactating or not using acceptable methods of contraception
* Clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders
* Clinically relevant surgical history
* Clinically relevant family history
* History of relevant atopy
* History of relevant drug hypersensitivity
* History of alcoholism
* History of drug abuse
* Male subjects who consumed more than 21 units of alcohol a week and female subjects who consumed more than 14 units of alcohol a week
* Significant infection or known inflammatory process on screening
* Acute gastrointestinal symptoms at the time of screening and/or admission (e.g. nausea, vomiting, diarrhoea, heartburn)
* Acute infection such as influenza at the time of screening or admission
* Use of prescription drugs within 7 days of first dosing, unless agreed as non clinically relevant by the Principal Investigator and Sponsor
* Use of over-the-counter medication excluding routine vitamins but including mega dose vitamin therapy within 14 days of first dosing, unless agreed as non clinically relevant by the Principal Investigator and Sponsor
* Use of any investigational drug or participation in any clinical trial within 3 months of their first dosing
* Donation or receipt of any blood or blood products within the previous 3 months prior to first dosing
* Vegetarians, vegans or having medical or cultural dietary restrictions.
* Inability to communicate reliably with the Investigator.
* Subjects who were unlikely to co-operate with the requirements of the study

Primary outcomes:
measure: Rate and extent of exposure
timeFrame: 0 to 36 hours post dose
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guy's Drug Research Unit, Quintiles Ltd
Study officials:
affiliation: Guy's Drug Research Unit, Quintiles Ltd
name: Darren Wilbraham
role: PRINCIPAL_INVESTIGATOR
References: