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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Analgesics
Analgesics, Non-Narcotic
Analgesics, Opioid
Antipyretics
Central Nervous System Agents
Central Nervous System Depressants
Narcotics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014