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

Labopharm

Status and phase: Completed; Phase 1

Conditions: Healthy

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT00973232

06CCL102

Details and patient eligibility

About

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.

Full 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.

Enrollment: 58 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

58 participants in 7 patient groups

Part A, Arm A

Experimental group

Treatment:

Drug: DDS-06C (650 mg acetaminophen and 75 mg tramadol HCl)

Part A, Arm B

Experimental group

Treatment:

Drug: DDS-06C (650 mg acetaminophen and 75 mg tramadol)

Part A, Arm C

Active Comparator group

Treatment:

Drug: Zaldiar®

Part A, Arm D

Active Comparator group

Treatment:

Drug: Ultracet®

Part B, Arm E

Experimental group

Treatment:

Drug: Two tablets of DDS-06C (650 mg acetaminophen and 75 mg tramadol HCl), multiple doses, under both fed and fasting conditions

Part B, Arm F

Active Comparator group

Treatment:

Drug: Zaldiar®, multiple doses,(fed & fasting):

Part B, Arm G

Active Comparator group

Treatment:

Drug: Ultracet®, multiple doses, (fed & fasting)