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®”

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.

Study Type: Interventional

Study Design: Allocation: Randomized, Control: Active Control, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Study Primary Completion Date: August 2008

- 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.

Intervention(s) in this Clinical Trial

• 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
• 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
• 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)
• 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)
• 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
• 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
• 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

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Part A, Arm A
• Experimental: Part A, Arm B
• Active Comparator: Part A, Arm C
• Active Comparator: Part A, Arm D
• Experimental: Part B, Arm E
• Active Comparator: Part B, Arm F
• Active Comparator: Part B, Arm G

Primary Measures

• Rate and extent of exposure
  • Time Frame: 0 to 36 hours post dose
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Labopharm Inc.

Overall Clinical Trial Officials and Contacts

Darren Wilbraham Principal Investigator Guy's Drug Research Unit, Quintiles Ltd  

Information obtained from ClinicalTrials.gov on September 07, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00973232

Study ID Number: 06CCL102

ClinicalTrials.gov Identifier: NCT00973232

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency