A Pharmacokinetic Study to Compare Sustained Release and Standard Paracetamol Formulations. - Full Text View

Purpose

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.

Condition	Intervention	Phase
Pain	Drug: Paracetamol 500 mg Drug: Paracetamol 1000 mg Drug: Paracetamol 750 mg	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Proof of Principal Study to Investigate the Pharmacokinetic Profiles of Sustained Release and Standard Paracetamol Formulations

Resource links provided by NLM:

Drug Information available for: Acetaminophen

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Median time to reach therapeutic plasma concentration of paracetamol [ Time Frame: 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 ] [ Designated as safety issue: No ]
Time period in hours over which plasma paracetamol concentration is elevated at or above 4 micrograms (μg)/milliliter (mL).

Secondary Outcome Measures:

Area under the plasma concentration-time curve (AUC) [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
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.
Time to maximum plasma concentration (Tmax) [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
Tmax for paracetamol to be determined.
Half-life of elimination (T 1/2) [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
T 1/2 of paracetamol to be determined.
Elimination rate (Kel) [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
Kel of paracetamol to be determined.
Maximum plasma concentration (Cmax) [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
Cmax of paracetamol to be determined.
Number of participants with Adverse Events (AEs) and Serious AEs [ Time Frame: Day 1 through Day 14 (follow-up visit) ] [ Designated as safety issue: Yes ]
Safety evaluation

Enrollment:	14
Study Start Date:	May 2010
Study Completion Date:	October 2010
Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01551797

Locations

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

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01551797 History of Changes
Other Study ID Numbers:	A2750894
Study First Received:	February 23, 2012
Last Updated:	December 6, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Acetaminophen
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic

Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013