Assessment of the Pharmacokinetics of a Sustained Release Formulation of a Tramadol/Acetaminophen Combination

Study Overview
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Brief Summary
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Objective: To evaluate the pharmacokinetic profiles of an SR 75 mg tramadol/650 mg acetaminophen formulation compared with an immediate release (IR) 37.5 mg tramadol/325 mg acetaminophen formulation after a single dose and at steady state Subjects: Healthy subject Methods: A phase I study to evaluate the pharmacokinetic sustained release and immediate release treatment profiles at steady state.

Detailed Description
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This study was open, randomized, 2-period, 2-treatment multiple-dose crossover study of immediate release treatment and sustained release treatment was designed to assess the pharmacokinetics after a 2-day repeated administration in which the steady state was achieved.

Official Title
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Clinical Trial to Compare the Pharmacokinetics Profile of YJAT Sustained Release Tablet and ULTRACET® Immediate Release Tablet After Oral Administration to Healthy Male Subjects

Conditions
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Pain

Intervention / Treatment
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* Drug: Tramadol HCI/Acetaminophen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects between the ages of 20 and 45 years Subjects weighed ≥ 45 kg and were within 20% of their ideal body weight No clinically relevant abnormalities identified by vital sign measurement, 12-lead electrocardiography and routine laboratory test Exclusion Criteria: Hypersensitivity or histories of sensitivity to either tramadol or acetaminophen Evidence or histories of clinically significant renal, digestive, respiratory, musculoskeletal, endocrine, psychiatric, neurological, hematological or cardiovascular diseases Taking any prescription or herbal medicines within 2 weeks before the study or any over-the-counter medication within 1 week before the study Systolic blood pressure (SBP) ≥ 160 mmHg or ≤ 100 mmHg or diastolic blood pressure (DBP) ≥ 95 mmHg or ≤ 60 mmHg Any surgical or medical conditions that could affect drug absorption

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group A<br>Period 1: Tramadol HCI/Acetaminophen 37.5/325mg PO once with water 240ml at fasted state Period 2: Tramadol HCI/Acetaminophen 75/650mg PO once once with water 240ml at fasted state | Drug: Tramadol HCI/Acetaminophen<br>* Test drug: Tramadol HCI/Acetaminophen 75/650mg, two times daily. Reference drug: Tramadol HCI/Acetaminophen 37.5/325 mg, four times daily.<br>* Other names: YJAT sustained release tablet;|
| Other: Group B<br>Period 1: Tramadol HCI/Acetaminophen 75/650mg PO once once with water 240ml at fasted state Period 2: Tramadol HCI/Acetaminophen 37.5/325mg PO once with water 240ml at fasted state | Drug: Tramadol HCI/Acetaminophen<br>* Test drug: Tramadol HCI/Acetaminophen 75/650mg, two times daily. Reference drug: Tramadol HCI/Acetaminophen 37.5/325 mg, four times daily.<br>* Other names: YJAT sustained release tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the pharmacokinetic profiles of tramadol and acetaminophen at steady state | Bio-equivalence of Cmax at steady state of tramadol and acetaminophen | 0 to 36 hour | 
| Evaluate the pharmacokinetic profiles of tramadol and acetaminophen at steady state | Bio-equivalence of AUC at steady state of tramadol and acetaminophen | 0 to 36 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the pharmacokinetics profiles of tramadol, acetaminophen and O-desmethyltramadol at steady state | Tmax of tramadol and acetaminophen at steady state. | 0 to 36 hour | 
| Evaluate the pharmacokinetics profiles of tramadol, acetaminophen and O-desmethyltramadol at steady state | Half-life of tramadol and acetaminophen at steady state. | 0 to 36 hour | 
| Evaluate the pharmacokinetics profiles of tramadol, acetaminophen and O-desmethyltramadol at steady state | Accumulation index of tramadol and acetaminophen at steady state. | 0 to 36 hour | 
| Evaluate the pharmacokinetics profiles of tramadol, acetaminophen and O-desmethyltramadol at steady state | Cmax of O-desmethyltramadol at steady state | 0 to 36 hour | 
| Evaluate the pharmacokinetics profiles of tramadol, acetaminophen and O-desmethyltramadol at steady state | AUC of O-desmethyltramadol at steady state | 0 to 36 hour | 
| Evaluate the pharmacokinetics profiles of tramadol, acetaminophen and O-desmethyltramadol at steady state | Tmax of O-desmethyltramadol at steady state | 0 to 36 hour | 
| Evaluate the pharmacokinetics profiles of tramadol, acetaminophen and O-desmethyltramadol at steady state | Half-life of O-desmethyltramadol at steady state | 0 to 36 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tramadol, Acetaminophen, Pharmacokinetics, Sustained release, Immediate release