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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Labopharm Inc.
ClinicalTrials.gov Identifier:
NCT00973232
First received: September 8, 2009
Last updated: April 24, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: DDS-06C (650 mg acetaminophen and 75 mg tramadol HCl)
Drug: DDS-06C (650 mg acetaminophen and 75 mg tramadol)
Drug: Zaldiar®
Drug: Ultracet®
Drug: Two tablets of DDS-06C (650 mg acetaminophen and 75 mg tramadol HCl), multiple doses, under both fed and fasting conditions
Drug: Zaldiar®, multiple doses,(fed & fasting):
Drug: Ultracet®, multiple doses, (fed & fasting)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
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®

Resource links provided by NLM:


Further study details as provided by Labopharm Inc.:

Primary Outcome Measures:
  • Rate and extent of exposure [ Time Frame: 0 to 36 hours post dose ] [ Designated as safety issue: No ]

Enrollment: 58
Study Start Date: May 2008
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A, Arm A Drug: DDS-06C (650 mg acetaminophen and 75 mg tramadol HCl)
DDS-06C (650 mg acetaminophen and 75 mg tramadol HCl: two tablets, single dose, total administered of 1300 mg acetaminophen/150 mg tramadol HCl under fasting conditions
Experimental: Part A, Arm B Drug: DDS-06C (650 mg acetaminophen and 75 mg tramadol)
DDS-06C (650 mg acetaminophen and 75 mg tramadol HCl: two tablets, single dose, total administered of 1300 mg acetaminophen/150 mg tramadol HCl under fed conditions
Active Comparator: Part A, Arm C Drug: Zaldiar®
Zaldiar® (325 mg acetaminophen and 37.5 mg tramadol HCl): two tablets; dose of 650 mg acetaminophen/75 mg tramadol HCl administered at Time = 0 hr (fasting)and second dose at Time = 6 hr (fed) Ultracet® (325 mg acetaminophen and 37.5 mg tramadol HCl)
Active Comparator: Part A, Arm D Drug: Ultracet®
Ultracet® (325 mg acetaminophen and 37.5 mg tramadol HCl)two tablets; dose of 650 mg acetaminophen/75 mg tramadol HCl administered at Time = 0 hr (fasting)and second dose at Time = 6 hr (fed) Ultracet® (325 mg acetaminophen and 37.5 mg tramadol HCl)
Experimental: Part B, Arm E Drug: Two tablets of DDS-06C (650 mg acetaminophen and 75 mg tramadol HCl), multiple doses, under both fed and fasting conditions
Two tablets of DDS-06C, twice daily at 12-hour intervals under fed conditions for the first 4 days, then under fasting conditions for the 5th day. The total daily dose administered was 2600 mg Acetaminophen/300 mg tramadol HCl
Active Comparator: Part B, Arm F Drug: Zaldiar®, multiple doses,(fed & fasting):
Two tablets of Zaldiar®, 4 times daily at 6-hour intervals under fed conditions for the first 4 days, then under fasting conditions for the 5th day. The total daily dose administered was 2600 mg Acetaminophen/300 mg tramadol HCl
Active Comparator: Part B, Arm G Drug: Ultracet®, multiple doses, (fed & fasting)
Two tablets of Ultracet®, 4 times daily at 6-hour intervals under fed conditions for the first 4 days, then under fasting conditions for the 5th day. The total daily dose administered was 2600 mg Acetaminophen/300 mg tramadol HCl

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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00973232

Locations
United Kingdom
Guy's Drug Research Unit, Quintiles Ltd
London, United Kingdom, SE1 1YR
Sponsors and Collaborators
Labopharm Inc.
Investigators
Principal Investigator: Darren Wilbraham Guy's Drug Research Unit, Quintiles Ltd
  More Information

No publications provided

Responsible Party: Labopharm Inc.
ClinicalTrials.gov Identifier: NCT00973232     History of Changes
Other Study ID Numbers: 06CCL102
Study First Received: September 8, 2009
Last Updated: April 24, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Labopharm Inc.:
Tramadol
Acetaminophen
combination
pharmacokinetics
bioavailability
Zaldiar
Ultracet
fed
fasted
single-dose
multiple-dose
healthy
volunteers
Healthy volunteers

Additional relevant MeSH terms:
Acetaminophen
Tramadol
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Narcotics
Central Nervous System Depressants
Analgesics, Opioid

ClinicalTrials.gov processed this record on April 21, 2014