Ibuprofen and Pseudoephedrine Comparative Pharmacokinetic Study

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Test Nurofen Cold and Flu®, Ibuprofen and pseudoephedrine liquid capsules; Drug: Comparator 1 Nurofen Cold and Flu®, ibuprofen and pseudoephedrine tablets; Drug: Comparator 2 Nurofen Immedia 200 mg Weichkapseln, ibuprofen liquid capsules

• Registration Number: NCT03184766
• Lead Sponsor: Reckitt Benckiser Healthcare (UK) Limited

Brief Summary

This comparative pharmacokinetic study is being conducted to provide supporting evidence for inclusion in dossiers to regulatory authorities for an Article 8(3) of Directive 2001/83/EC abridged application for ibuprofen and pseudoephedrine liquid capsules (200 mg ibuprofen \& 30 mg pseudoephedrine).

Detailed Description

Not available

Study Timeline

• Study Start: 2016-08-10
• Primary Completion: 2017-01-30
• Study Completion: 2017-01-30
• Status Verified: 2017-04
• Study First Submitted: 2017-05-17
• Study First Submitted QC: 2017-06-08
• Last Update Submitted: 2017-06-08
• Study First Posted: 2017-06-14
• Last Update Posted: 2017-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 55

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 ≥ 20 and ≤ 30 kg/m2.
4. Healthy as determined by past medical history, physical examination, vital signs, electrocardiogram, 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 psychiatric disorders.
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, other NSAIDs, pseudoephedrine, other sympathomimetic or catecholamine derivative decongestant drugs or the excipients of the formulations.
5. A history of or active peptic or duodenal ulcers or gastro-intestinal bleed or upper gastro-intestinal bleed, or other significant gastro-intestinal disorders.
6. A history of hypertension or hypertension that is currently treated with antihypertensive medication.
7. A history of frequent dyspepsia, e.g. heartburn or indigestion.
8. A history of migraine.
9. Current smokers and ex-smokers who have smoked or used nicotine replacement products during the previous 6 months prior to first dosing.
10. A history of substance abuse (including alcohol).
11. High consumption of stimulating drinks (coffee, tea, cola, energy drinks etc.; total caffeine intake per day above 300 mg).
12. Those with positive screen/test for drugs of abuse and alcohol.
13. Those with a positive screen for ibuprofen.
14. 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.
15. Ingestion of an over-the-counter preparation within 7 days before the first dose of study medication, including herbal medications, vitamin/fish oil supplements, ibuprofen, other NSAIDs or decongestants.
16. Donation of blood in quantity > 400 ml e.g. to the blood transfusion service in the 12 weeks prior to the first dose of study medication
17. Known human immune deficiency virus (HIV) positive status, or a positive viral serology screen.
18. Topical use of ibuprofen within 7 days before the 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. Those who have participated in a clinical trial in the 12 weeks prior to the first dose of study medication.
23. Those unable in the opinion of the Investigator to comply fully with the study requirements.
24. Those who have consumed grapefruit or grapefruit juice, pummelo or Seville oranges in the 7 days prior to randomisation.
25. Those who are unwilling to consume gelatine of animal origin.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
5	Comparator 1 Nurofen Cold and Flu®, ibuprofen and pseudoephedrine tablets	Treatment Order: Comparator 2, Test, Comparator 1
5	Test Nurofen Cold and Flu®, Ibuprofen and pseudoephedrine liquid capsules	Treatment Order: Comparator 2, Test, Comparator 1
6	Comparator 1 Nurofen Cold and Flu®, ibuprofen and pseudoephedrine tablets	Treatment Order: Comparator 2, Comparator 1, Test
3	Comparator 1 Nurofen Cold and Flu®, ibuprofen and pseudoephedrine tablets	Treatment Order: Comparator 1, Test, Comparator 2
1	Test Nurofen Cold and Flu®, Ibuprofen and pseudoephedrine liquid capsules	Treatment Order: Test, Comparator 1, Comparator 2
2	Comparator 2 Nurofen Immedia 200 mg Weichkapseln, ibuprofen liquid capsules	Treatment Order: Test, Comparator 2, Comparator 1
2	Test Nurofen Cold and Flu®, Ibuprofen and pseudoephedrine liquid capsules	Treatment Order: Test, Comparator 2, Comparator 1
4	Comparator 1 Nurofen Cold and Flu®, ibuprofen and pseudoephedrine tablets	Treatment Order: Comparator 1, Comparator 2, Test
1	Comparator 2 Nurofen Immedia 200 mg Weichkapseln, ibuprofen liquid capsules	Treatment Order: Test, Comparator 1, Comparator 2
2	Comparator 1 Nurofen Cold and Flu®, ibuprofen and pseudoephedrine tablets	Treatment Order: Test, Comparator 2, Comparator 1
1	Comparator 1 Nurofen Cold and Flu®, ibuprofen and pseudoephedrine tablets	Treatment Order: Test, Comparator 1, Comparator 2
4	Comparator 2 Nurofen Immedia 200 mg Weichkapseln, ibuprofen liquid capsules	Treatment Order: Comparator 1, Comparator 2, Test
6	Comparator 2 Nurofen Immedia 200 mg Weichkapseln, ibuprofen liquid capsules	Treatment Order: Comparator 2, Comparator 1, Test
3	Test Nurofen Cold and Flu®, Ibuprofen and pseudoephedrine liquid capsules	Treatment Order: Comparator 1, Test, Comparator 2
4	Test Nurofen Cold and Flu®, Ibuprofen and pseudoephedrine liquid capsules	Treatment Order: Comparator 1, Comparator 2, Test
5	Comparator 2 Nurofen Immedia 200 mg Weichkapseln, ibuprofen liquid capsules	Treatment Order: Comparator 2, Test, Comparator 1
3	Comparator 2 Nurofen Immedia 200 mg Weichkapseln, ibuprofen liquid capsules	Treatment Order: Comparator 1, Test, Comparator 2
6	Test Nurofen Cold and Flu®, Ibuprofen and pseudoephedrine liquid capsules	Treatment Order: Comparator 2, Comparator 1, Test

Primary Outcome Measures

Name	Time	Method
Pseudoephedrine AUC0-t for Test vs. Comparator 1.	PK Analysis: 0-48hrs	The Test and Comparator 1 will be considered similar if for pseudoephedrine, for each corresponding PK parameter, the 90% confidence interval for the Test to Comparator 1 ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%:
Pseudoephedrine Cmax for Test vs. Comparator 1.	PK Analysis: 0-48hrs	The Test and Comparator 2 will be considered similar if for ibuprofen, for each corresponding PK parameter, the 90% confidence interval for the Test to Comparator 2 ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%:
Ibuprofen AUC0-t for Test vs. Comparator 2.	PK Analysis: 0-48hrs	The Test and Comparator 2 will be considered similar if for ibuprofen, for each corresponding PK parameter, the 90% confidence interval for the Test to Comparator 2 ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%:
Ibuprofen Cmax for Test vs. Comparator 2.	PK Analysis: 0-48hrs	The Test and Comparator 2 will be considered similar if for ibuprofen, for each corresponding PK parameter, the 90% confidence interval for the Test to Comparator 2 ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%:

Secondary Outcome Measures

Name	Time	Method
Ibuprofen AUC0-t for Test vs. Comparator 1.	PK Analysis: 0-48hrs	The Test and Comparator 1 will be considered similar if for ibuprofen, for each corresponding PK parameter, the 90% confidence interval for the Test to Comparator 1 ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%: • Cmax for ibuprofen (in the context of the Test vs. Comparator 1 comparison)
Ibuprofen Cmax for Test vs. Comparator 1.	PK Analysis: 0-48hrs	The Test and Comparator 1 will be considered similar if for ibuprofen, for each corresponding PK parameter, the 90% confidence interval for the Test to Comparator 1 ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%:
Assessment of how fast the ibuprofen from the Test product starts to be absorbed and how quickly it reaches the therapeutic level.	PK Analysis: 0-48hrs	T8.4 - time to reach the therapeutic level (8.4 µg/ml) for ibuprofen.
Pharmacokinetic parameters will be assessed as secondary endpoints.	PK Analysis: 0-48hrs	Tlag - time between administration and the beginning of absorption of ibuprofen. This will be calculated only for the Test.