At What Time Therapeutic Plasma Concentrations of Paracetamol Are Achieved in Two Marketed Formulations

A Randomised, Two Way Crossover Study to Determine the Time at Which Therapeutic Plasma Concentrations of Paracetamol Are Achieved in Two Marketed Formulations

This will be a single centre, open label, randomised, two-way crossover study in healthy volunteers under semi-fed conditions. Two formulations of paracetamol, are being tested in this study to establish at what time point a therapeutic concentration of paracetamol in the blood is reached. Subjects will attend a screening visit to check if they are eligible for study participation then within 15 days they will check-in to the unit for a stay of approximately 48 hours (hrs). They will be given a single dose of one of the preparations on the first day and then the other preparation on the next day. Regular blood samples will be taken along with other assessments for safety.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: Paracetamol formulation 1; Drug: Paracetamol formulation 2

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • N Ireland
    • Belfast, N Ireland, United Kingdom, BT9 6AD
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Males in good general heatlh and Body Mass Index between 19-28 kg/m2

Exclusion Criteria:

• Disease

  1. Current liver impairment, renal impairment, history of or active gastrointestinal ulcers, uncontrolled hypertension, haemophilia or other bleeding disorders.
  2. Current or recurrent disease, within 12 months of the screening, that could affect the action, absorption or disposition of the study formulations or clinical or laboratory assessments (e.g. hepatic disorders, renal insufficiency, congestive heart failure).
  3. Current or relevant previous history, within 12 months of the screening visit, of serious, severe or unstable physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the study treatments or procedures.

• Medications

  1. Current or regular use at screening of any prescription, herbal or Over the Counter (OTC) medication including paracetamol, aspirin, metaclopramide, domperidone, cholestyramine, angiotensin -converting enzyme (ACE) inhibitors, acetazolamide, anticonvulsants, diuretics, methotrexate, non-steroidal anti-inflammatory drugs (NSAIDs) and oral hypoglycemics within the past 48 hrs and monoamine oxidase inhibitors, tricyclic antidepressants, beta blockers and anticoagulants such as warfarin and heparin within the past 2 weeks.
  2. Subjects who have taken any drug known to induce or inhibit hepatic drug metabolism in the 30 days prior to the screening visit (some examples of inducers: barbiturates, theophylline; inhibitors: cimetidine, erythromycin).
  3. Subjects for whom the use of any of the study drugs is contraindicated.
• Virology Screening Positive screening for serum Hepatitis B surface antigen, Hepatitis C antibodies or human immunodeficiency virus (HIV).

• Drug Screen

  1. Positive urine screen for drugs of abuse at screening and/or Day-1.
  2. Positive alcohol breath test on Day-1.

• Smoking

  1. Smoking more than five cigarettes a day.
  2. Prior (within 7 days of dosing on Day 1) or current use of any other nicotine containing products, other than cigarettes/pipes/cigars.
• Blood donation Has donated blood or plasma or any other blood product within 3 months of the screening visit. Subjects for whom participation in this study would result in having donated more than 1500 ml of blood within the previous 12 months.

• Nutrition

  1. Is a vegetarian or is under a sodium restricted diet.
  2. Has consumed poppy seed containing foods within 3 days prior to the screening visit and admission on Day -1.
  3. Has consumed food and beverages containing grapefruit, Seville oranges or marmalade within 24 hrs prior to admission on Day -1.
  4. Has consumed caffeine containing drinks or food (e.g. tea, coffee, chocolate and cola) 24 hrs prior to admission on Day -1.
  5. Has consumed alcohol 36 hrs prior to admission on Day -1.
• Has undertaken any unusually strenuous physical activity 24 hrs prior to the screening visit or check-in on Day 1.
• Weight Weight below 50 kg.
• Haemoglobin Subjects with haemoglobin level below 12.0 gram /decilitre (dl).

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Paracetamol formulation 1; Higher dose level of marketed paracetamol (compared to the other dosage arm)	Drug: Paracetamol formulation 1; formulation 1
Other: Paracetamol formulation 2; Lower paracetamol concentrations	Drug: Paracetamol formulation 2; Formulation 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean time to therapeutic levels of plasma concentration	within a single day

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean plasma concentrations	within a single day

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: June 23, 2011
• First Submitted That Met QC Criteria: March 8, 2012
• First Posted (Estimate): March 13, 2012

Study Record Updates

• Last Update Posted (Estimate): March 13, 2012
• Last Update Submitted That Met QC Criteria: March 8, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: pharmacokinetics; paracetamol
• 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: E3870651