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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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®

Conditions
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Healthy

Intervention / Treatment
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* 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)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A, Arm A<br> | Drug: DDS-06C (650 mg acetaminophen and 75 mg tramadol HCl)<br>* 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<br>|
| Experimental: Part A, Arm B<br> | Drug: DDS-06C (650 mg acetaminophen and 75 mg tramadol)<br>* 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<br>|
| Active Comparator: Part A, Arm C<br> | Drug: Zaldiar®<br>* 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)<br>|
| Active Comparator: Part A, Arm D<br> | Drug: Ultracet®<br>* 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)<br>|
| Experimental: Part B, Arm E<br> | Drug: Two tablets of DDS-06C (650 mg acetaminophen and 75 mg tramadol HCl), multiple doses, under both fed and fasting conditions<br>* 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<br>|
| Active Comparator: Part B, Arm F<br> | Drug: Zaldiar®, multiple doses,(fed & fasting):<br>* 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<br>|
| Active Comparator: Part B, Arm G<br> | Drug: Ultracet®, multiple doses, (fed & fasting)<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fed, Tramadol, Acetaminophen, combination, pharmacokinetics, bioavailability, Zaldiar, Ultracet, fasted, single-dose, multiple-dose, healthy, volunteers, Healthy volunteers