Ibuprofen Bioavailability Study

An Open Label, Randomised, Single Dose, Three-way Crossover Study to Compare the Bioavailability of 400 mg Ibuprofen From 2 x 200 mg Ibuprofen Acid Orodispersable Tablets, 2x 200 mg Ibuprofen Acid Tablets and 2 x 342 mg Ibuprofen Lysine Tablets in Fasted Healthy Volunteers

This project is the in-house development of a 200 mg ibuprofen acid orodispersable tablet (ODT; meltlet). It is designed to appeal to consumers who want a dosage form that may be taken without water and can be used 'on the go'. Vanquish has an improved organoleptic profile compared to the currently marketed meltet by the Sponsor. ODTs are also considered as a suitable dosage form for children who may be reluctant to swallow tablets. This product has the potential for application in both adults and children due to the convenience of the format and the ease of administration for both groups.

This will be the first pharmacokinetic (PK) assessment of the ibuprofen acid ODT formulation.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Test - RB ibuprofen acid orodispersible tablets; Drug: Reference - RB Nurofen ibuprofen acid tablets; Drug: Comparator - Dolormin ibuprofen lysine tablets

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Merthyr Tydfil, United Kingdom
    • Simbec Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects who have given written informed consent.
2. Age: ≥ 18 years ≤ 50 years.
3. Body Mass Index (BMI) of ≥ 18.0 and ≤ 30 kg/m2.
4. Healthy as determined by past medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory tests at screening.
5. Female subject of child bearing potential with a negative pregnancy test at the screening visit and willing to use an effective method of contraception unless of non-childbearing potential or where abstaining from sexual intercourse in line with the preferred and usual lifestyle of the subject from first dose until 3 months after the final dose of study medication.
6. Female subject of non-child bearing potential with negative pregnancy test at the screening visit.
7. Male subject willing to use an effective method of contraception unless anatomically sterile or where abstaining from sexual intercourse in line with the preferred and usual lifestyle of the subject from first dose until 3 months after the final dose of study medication.

Exclusion Criteria:

1. Pregnant or lactating females.
2. A history and/or presence of significant disease of any body system, including significant psychiatric disorders, parasuicide.
3. Any condition that may currently interfere with the absorption, distribution, metabolism or excretion of drugs.
4. A history of allergy or intolerance related to treatment with ibuprofen, aspirin or other non-steriodal anti-inflammatory drugs (NSAIDs), or the excipients of the formulations
5. A history of or active peptic or duodenal ulcers or gastrointestinal bleed or upper gastro-intestinal bleed, or other significant gastro-intestinal disorders.
6. A history of frequent dyspepsia, e.g. heartburn or indigestion.
7. A history of significant and frequent migraine.
8. Current smokers or ex-smokers who have smoked or used nicotine replacement products during the 6 months prior to the first dose of study medication.
9. A history of substance abuse (including alcohol).
10. Consumption of foods or beverages containing caffeine (e.g. coffee, tea, cola and chocolate) above 300 mg caffeine per day, prior to 48 hours of each treatment period. (One cup of coffee equals approximately 50 mg caffeine).
11. Those with positive test for drugs of abuse and alcohol.
12. Ingestion of a prescribed drug at any time in the 14 days before the first dose of study medication (excluding hormonal contraceptives and hormone replacement therapy), or consumption of enzyme inhibitors or inducers 30 days prior to the first dose of study medication (such as barbiturates, carbamazepine, erythromycin, phenytoin, etc.).
13. Ingestion of an over-the-counter preparation within 7 days before the first dose of study medication, including herbal medications, vitamins, fish oil supplements, ibuprofen and other NSAIDs.
14. Those who have consumed grapefruit or grapefruit juice, pumelo or Seville oranges in the 7 days before the first dose of study medication.
15. Donation of blood > 400 mL e.g. to the blood transfusion service in the 12 weeks prior to the first dose of study medication.
16. Known human immune deficiency virus (HIV) positive status, or a positive viral serology test.
17. Topical use of ibuprofen within 7 days before the first dose of study medication.
18. Strenuous physical exercise from 48 hours prior to first dose of study medication.
19. Those previously randomised into this study.
20. Those who are an employee at the study site.
21. Those who are a partner or first degree relative of the Investigator.
22. Participation in a New Chemical Entity clinical study within the previous 3 months or a marketed drug clinical study within the 30 days before the first dose of study medication.
23. 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: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Treatment Order: Test, Reference, Comparator	Drug: Test - RB ibuprofen acid orodispersible tablets; RB ibuprofen acid orodispersible tablets, 2 x 200 mg, single dose, oral.; Drug: Reference - RB Nurofen ibuprofen acid tablets; RB Nurofen ibuprofen acid tablets, 2 x 200 mg, single dose, oral.; Drug: Comparator - Dolormin ibuprofen lysine tablets; Dolormin ibuprofen lysine tablets 2 x 342 mg (each 342 mg tablet contains 200 mg ibuprofen), single dose, oral.
Experimental: 2; Treatment Order: Test, Comparator, Reference	Drug: Test - RB ibuprofen acid orodispersible tablets; RB ibuprofen acid orodispersible tablets, 2 x 200 mg, single dose, oral.; Drug: Reference - RB Nurofen ibuprofen acid tablets; RB Nurofen ibuprofen acid tablets, 2 x 200 mg, single dose, oral.; Drug: Comparator - Dolormin ibuprofen lysine tablets; Dolormin ibuprofen lysine tablets 2 x 342 mg (each 342 mg tablet contains 200 mg ibuprofen), single dose, oral.
Experimental: 3; Treatment Order: Reference, Test, Comparator	Drug: Test - RB ibuprofen acid orodispersible tablets; RB ibuprofen acid orodispersible tablets, 2 x 200 mg, single dose, oral.; Drug: Reference - RB Nurofen ibuprofen acid tablets; RB Nurofen ibuprofen acid tablets, 2 x 200 mg, single dose, oral.; Drug: Comparator - Dolormin ibuprofen lysine tablets; Dolormin ibuprofen lysine tablets 2 x 342 mg (each 342 mg tablet contains 200 mg ibuprofen), single dose, oral.
Experimental: 4; Treatment Order: Reference, Comparator, Test	Drug: Test - RB ibuprofen acid orodispersible tablets; RB ibuprofen acid orodispersible tablets, 2 x 200 mg, single dose, oral.; Drug: Reference - RB Nurofen ibuprofen acid tablets; RB Nurofen ibuprofen acid tablets, 2 x 200 mg, single dose, oral.; Drug: Comparator - Dolormin ibuprofen lysine tablets; Dolormin ibuprofen lysine tablets 2 x 342 mg (each 342 mg tablet contains 200 mg ibuprofen), single dose, oral.
Experimental: 5; Treatment Order: Comparator, Test, Reference	Drug: Test - RB ibuprofen acid orodispersible tablets; RB ibuprofen acid orodispersible tablets, 2 x 200 mg, single dose, oral.; Drug: Reference - RB Nurofen ibuprofen acid tablets; RB Nurofen ibuprofen acid tablets, 2 x 200 mg, single dose, oral.; Drug: Comparator - Dolormin ibuprofen lysine tablets; Dolormin ibuprofen lysine tablets 2 x 342 mg (each 342 mg tablet contains 200 mg ibuprofen), single dose, oral.
Experimental: 6; Treatment Order: Comparator, Reference, Test	Drug: Test - RB ibuprofen acid orodispersible tablets; RB ibuprofen acid orodispersible tablets, 2 x 200 mg, single dose, oral.; Drug: Reference - RB Nurofen ibuprofen acid tablets; RB Nurofen ibuprofen acid tablets, 2 x 200 mg, single dose, oral.; Drug: Comparator - Dolormin ibuprofen lysine tablets; Dolormin ibuprofen lysine tablets 2 x 342 mg (each 342 mg tablet contains 200 mg ibuprofen), single dose, oral.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-t - the area under plasma concentration curve from administration to last quantifiable concentration at time t.	The Test and Reference will be considered similar if for ibuprofen, for each corresponding PK parameter, the 90% confidence interval for the Test to Reference ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%:	PK Analysis 0-12hrs
Cmax - the maximum observed plasma concentration.	The Test and Reference will be considered similar if for ibuprofen, for each corresponding PK parameter, the 90% confidence interval for the Test to Reference ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%:	PK Analysis 0-12hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-t - the area under plasma concentration curve from administration to last quantifiable concentration at time t.	The Test and Comparator will be considered similar if for ibuprofen, for each corresponding PK parameter, the 90% confidence interval for the Test to Comparator ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%:	PK Analysis 0-12hrs
Cmax - the maximum observed plasma concentration.	The Test and Comparator will be considered similar if for ibuprofen, for each corresponding PK parameter, the 90% confidence interval for the Test to Comparator ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%:	PK Analysis 0-12hrs
Kel - Elimination rate constant	Secondary endpoint for Test, Reference and Comparator products	PK Analysis 0-12hrs
AUC0-inf - Area under the plasma concentration-time curve from administration to infinity	Secondary endpoint for Test, Reference and Comparator products	PK Analysis 0-12hrs
AUCR - Ratio AUC0-t/AUC0-inf	Secondary endpoint for Test, Reference and Comparator products	PK Analysis 0-12hrs
Tmax - Time until Cmax is first achieved	Secondary endpoint for Test, Reference and Comparator products	PK Analysis 0-12hrs
T1/2 - Plasma concentration (elimination) half-life	Secondary endpoint for Test, Reference and Comparator products	PK Analysis 0-12hrs
Cn - The plasma concentration at each planned nominal time point.	Secondary endpoint for Test, Reference and Comparator products	PK Analysis 0-12hrs

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall proportion of subjects with adverse events (AEs), i.e. the occurrence of one or more AEs per subject		Through study completion - Screening to study follow-up (approx 6 weeks)
Change from baseline in oral temperature.	Measured in degrees Celcius	Through study completion - Screening to study follow-up (approx 6 weeks)
Change from baseline in resting heart rate.	Measured in beats per minute	Through study completion - Screening to study follow-up (approx 6 weeks)
Change from baseline in resting blood pressure..	Measured in mmHg	Through study completion - Screening to study follow-up (approx 6 weeks)
Change from baseline in standard haematology testing.		Through study completion - Screening to study follow-up (approx 6 weeks)
Change from baseline in standard biochemistry testing.		Through study completion - Screening to study follow-up (approx 6 weeks)
Change from baseline in standard urinary testing.		Through study completion - Screening to study follow-up (approx 6 weeks)

Collaborators and Investigators

• Sponsor: Reckitt Benckiser Healthcare (UK) Limited
• Collaborators: Simbec Research
• Investigators: Principal Investigator: Annelize Koch, MBBS, Simbec Research

Publications and helpful links

General Publications

• Sugar D, Francombe D, da Silva T, Hanid S, Hutchings S. Comparative Bioavailability Study of a New Orodispersible Formulation of Ibuprofen Versus Two Existing Oral Tablet Formulations in Healthy Male and Female Volunteers. Clin Ther. 2019 Aug;41(8):1486-1498. doi: 10.1016/j.clinthera.2019.04.040. Epub 2019 Jun 12.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2017
• Primary Completion (Actual): June 13, 2017
• Study Completion (Actual): June 13, 2017

Study Registration Dates

• First Submitted: May 17, 2017
• First Submitted That Met QC Criteria: June 6, 2017
• First Posted (Actual): June 8, 2017

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: October 4, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• 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: RB7-UK-1604

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No