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

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

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.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Paracetamol 1000 mg; Drug: Paracetamol 750 mg; Drug: Paracetamol 500 mg

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Tacoma, Washington, United States, 98481
      • Charles River Clinical Services Northwest, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Sustained Release (SR) Paracetamol (2000 mg); A single 2000 mg oral dose of SR paracetamol formulation (2 x 1000 mg) administered with 150 mL of water.	Drug: Paracetamol 1000 mg; Paracetamol Sustained Release formulation
Experimental: Test SR Paracetamol (1500 mg); A single 1500 mg oral dose of SR paracetamol formulation (2 x 750 mg) administered with 150 mL of water.	Drug: Paracetamol 750 mg; Paracetamol Sustained Release formulation
Active Comparator: Reference Paracetamol (2000 mg); 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; Standard Paracetamol formulation

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: February 23, 2012
• First Submitted That Met QC Criteria: March 8, 2012
• First Posted (Estimate): March 13, 2012

Study Record Updates

• Last Update Posted (Estimate): December 10, 2012
• Last Update Submitted That Met QC Criteria: December 6, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: A2750894