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

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 Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: 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)

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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 1YR
    • Guy's Drug Research Unit, Quintiles Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate and extent of exposure	0 to 36 hours post dose

Collaborators and Investigators

• Sponsor: Labopharm Inc.
• Investigators: Principal Investigator: Darren Wilbraham, Guy's Drug Research Unit, Quintiles Ltd

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: September 8, 2009
• First Submitted That Met QC Criteria: September 8, 2009
• First Posted (Estimate): September 9, 2009

Study Record Updates

• Last Update Posted (Estimate): April 25, 2012
• Last Update Submitted That Met QC Criteria: April 24, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Healthy volunteers; pharmacokinetics; volunteers; bioavailability; healthy; Acetaminophen; fed; fasted; combination; Tramadol; multiple-dose; single-dose; Zaldiar; Ultracet
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Analgesics, Opioid; Narcotics; Acetaminophen; Tramadol
• Other Study ID Numbers: 06CCL102