A Pharmacokinetic Study to Compare Sustained Release and Standard Paracetamol Formulations.

Study Overview
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Brief Summary
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This proof of principle study will evaluate an experimental formulation of paracetamol that is being developed for eventual long lasting use. This study is also used for drug safety evaluation.

Official Title
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A Proof of Principal Study to Investigate the Pharmacokinetic Profiles of Sustained Release and Standard Paracetamol Formulations

Conditions
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Pain

Intervention / Treatment
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* Drug: Paracetamol 500 mg
* Drug: Paracetamol 1000 mg
* Drug: Paracetamol 750 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI): Body Mass Index must be in the range 19-28 kg/m2. Exclusion Criteria: Disease: Current or recurrent disease that could affect the action, absorption, elimination or disposition of the study medication or clinical or laboratory assessments (e.g. hepatic disorders evidenced by abnormal liver function test, hepatitis serology test and liver image studies, renal insufficiency, congestive heart failure). Current or relevant previous history of serious, severe or unstable physical or psychiatric illness, any medical disorder that may require treatment or make the participant unlikely to fully complete the study, or any condition that presents undue risk from the study medication or procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Sustained Release (SR) Paracetamol (2000 mg)<br>A single 2000 mg oral dose of SR paracetamol formulation (2 x 1000 mg) administered with 150 mL of water. | Drug: Paracetamol 1000 mg<br>* Paracetamol Sustained Release formulation<br>|
| Experimental: Test SR Paracetamol (1500 mg)<br>A single 1500 mg oral dose of SR paracetamol formulation (2 x 750 mg) administered with 150 mL of water. | Drug: Paracetamol 750 mg<br>* Paracetamol Sustained Release formulation<br>|
| Active Comparator: Reference Paracetamol (2000 mg)<br>Two single 1000 mg doses of paracetamol (2 x 500 mg/dose) administered orally 6 hours apart, administered with 150 mL of water. | Drug: Paracetamol 500 mg<br>* Standard Paracetamol formulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median time to reach therapeutic plasma concentration of paracetamol | Time period in hours over which plasma paracetamol concentration is elevated at or above 4 micrograms (μg)/milliliter (mL). | Baseline, 15 min, 30 min, 45 min, 1, 1.5 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 14, 15, 16, and 18 hours post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve (AUC) | Area under the plasma concentration-time curve from zero to 6 hours (AUC 0-6 hours), 12 hours (AUC 0-12 hours) to be determined. AUC0-t : the area under the plasma concentration-time curve from zero to time t when paracetamol remains detectable. AUC0-∞: the area under the plasma concentration time curve from zero and extrapolated to infinity time. | Baseline, 15 min, 30 min, 45 min, 1, 1.5 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 14, 15, 16, and 18 hours post-treatment | 
| Time to maximum plasma concentration (Tmax) | Tmax for paracetamol to be determined. | Baseline, 15 min, 30 min, 45 min, 1, 1.5 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 14, 15, 16, and 18 hours post-treatment | 
| Half-life of elimination (T 1/2) | T 1/2 of paracetamol to be determined. | Baseline, 15 min, 30 min, 45 min, 1, 1.5 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 14, 15, 16, and 18 hours post-treatment | 
| Elimination rate (Kel) | Kel of paracetamol to be determined. | Baseline, 15 min, 30 min, 45 min, 1, 1.5 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 14, 15, 16, and 18 hours post-treatment | 
| Maximum plasma concentration (Cmax) | Cmax of paracetamol to be determined. | Baseline, 15 min, 30 min, 45 min, 1, 1.5 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 14, 15, 16, and 18 hours post-treatment | 
| Number of participants with Adverse Events (AEs) and Serious AEs | Safety evaluation | Day 1 through Day 14 (follow-up visit) |