Ibuprofen Suspension Bioequivalence Study

A Randomized, Single-dose, 4-way Crossover, Open-label, Pharmacokinetic (PK) Study Comparing a 2% (w/v) Suspension of Ibuprofen (400 mg/20 mL Nurofen for Children®) With a Swiss Reference 2% (w/v) Suspension of Ibuprofen (400 mg/20 mL Algifor Dolo Junior®) in the Fed and Fasted States

The purpose of this study was to determine the rate and extent of absorption of Ibuprofen suspension formulations.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer Study
• Intervention / Treatment: Drug: Nurofen for Children®; Drug: Algifor Dolo Junior®

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Hull, United Kingdom
    • Reckit Benckiser

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who have given written informed consent.
• Age: ≥18 years ≤50 years.
• Sex: Male or female subjects are eligible for entry.
• Female subject of child bearing potential with a negative pregnancy test at the screening visit and willing to use an effective method of contraception,
• Female subject of non-child bearing potential with negative pregnancy test at the screening visit
• Male subject willing to use an effective method of contraception, unless anatomically sterile
• Status: Healthy subjects as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
• Healthy Subjects with a Body Mass Index (BMI) of ≥20 and ≤27 kg/m2

Exclusion Criteria:

• Pregnancy or lactating female subjects.
• A history of significant disease of any body system.
• Any condition that may currently interfere with the absorption, distribution, metabolism or excretion of drugs.
• A history of allergy or intolerance related to treatment with ibuprofen, aspirin or other Non-Steroidal Anti-inflammatory Drug,or the excipients of the formulations.
• A history of or active peptic or duodenal ulcers or gastro-intestinal bleed or upper gastro-intestinal bleed, or other significant gastro-intestinal disorders.
• A history of frequent dyspepsia, e.g. heartburn or indigestion.
• A history of migraine.
• Current smokers and ex-smokers who have smoked within 6 months.
• A history of drug abuse (including alcohol).
• High consumption of stimulating drinks (caffeine intake per day above 300 mg).
• Those with positive drugs of abuse screen including alcohol on any occasion throughout the study.
• Ingestion of a prescribed drug at any time in the 14 days before dosing with study medication (excluding hormonal contraceptives and hormone replacement therapy), or consumption of enzyme inhibitors or inducers during the previous month (such as barbiturates, carbamazepine, erythromycin, phenytoin, etc.).
• Ingestion of an over-the-counter preparation within 7 days before dosing with study medication.
• Donation of blood in quantity in the previous 12 weeks before enrolment into the study.
• Known human immune deficiency virus (HIV) positive status, or a positive viral serology screen.
• Topical use of ibuprofen within 7 days before dosing with study medication.
• Those previously randomised into this study.
• Employee at study site.
• Partner or first degree relative of the Investigator.
• Those who have participated in a clinical trial in the previous 12 weeks.
• Those unable in the opinion of the Investigator to comply fully with the study requirements.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nurofen for Children® (fasted); Nurofen for Children® suspension 400 mg/20 mL single-oral dose under fasted condition	Drug: Nurofen for Children®; Other Names: Ibuprofen orange oral suspension
Experimental: Nurofen for Children® (fed); Nurofen for Children® suspension 400 mg/20 mL single-oral dose under fed condition	Drug: Nurofen for Children®; Other Names: Ibuprofen orange oral suspension
Active Comparator: Algifor Dolo Junior® (fasted); Algifor Dolo Junior® suspension 400 mg/20 mL single-oral dose under fasted condition	Drug: Algifor Dolo Junior®; Other Names: Ibuprofen oral suspension
Active Comparator: Algifor Dolo Junior® (fed); Algifor Dolo Junior® suspension 400 mg/20 mL single-oral dose under fed condition	Drug: Algifor Dolo Junior®; Other Names: Ibuprofen oral suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Plasma Concentration (Cmax)	Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Area Under the Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t)	Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Elimination Rate Constant (Kel)		Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
AUC From Administration to Infinity (AUC0-inf)	AUC0-inf = AUC0-t + (Ct/Kel), where Ct was the last quantifiable concentration at time t.	Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Ratio of AUC0-t/AUC0-inf (AUCR)		Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Time to Cmax (Tmax)		Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Plasma Concentration Half-life (T1/2)	Terminal elimination half-life (T1/2) = ln(2)/Kel	Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Plasma Concentration at Each Planned Nominal Time-point (Cn)	Cn was derived using linear interpolation from the 2 samples taken either side of the nominal time where there was a sampling time deviation. For concentrations that were missing due to blood samples not being taken Cn was not derived.	Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Number of Subjects With Adverse Events (AEs).	Intensity was determined by the Investigator. For symptomatic AEs the following definitions were applied. Mild = AE did not limit usual activities; subject may have experienced slight discomfort. Moderate = AE resulted in some limitation of usual activities; subject may have experienced significant discomfort. Severe = AE resulted in an inability to carry out usual activities; subject may have experienced intolerable discomfort/pain. Relationship to Investigational Medicinal Products (IMP) Unassessable/Unclassified = Insufficient information to be able to make an assessment. Conditional/ Unclassified = Insufficient information to make an assessment at present. Unrelated = No possibility that AE was caused by IMP. Unlikely = Slight, but remote, chance that AE was caused by IMP. Possible = Reasonable suspicion that the AE was caused by IMP. Probable = Most likely that AE was caused by IMP. Certain = AE was definitely caused by IMP.	Up to follow-up day 7

Collaborators and Investigators

• Sponsor: Reckitt Benckiser Healthcare (UK) Limited

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2015
• Primary Completion (Actual): August 25, 2015
• Study Completion (Actual): August 25, 2015

Study Registration Dates

• First Submitted: July 13, 2015
• First Submitted That Met QC Criteria: July 16, 2015
• First Posted (Estimate): July 20, 2015

Study Record Updates

• Last Update Posted (Actual): April 13, 2018
• Last Update Submitted That Met QC Criteria: April 11, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Ibuprofen
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: NL1304; 2013-003366-14 (EudraCT Number)