Naproxen Sodium (2 x 220 mg) Fasted Comparative Bioavailability Study

A Randomised, Single-dose, 2-way Crossover, Open-label, Comparative Bioavailability Study Comparing Test Naproxen Sodium Tablets (2 x 220 mg) With Commercially Available Reference Naproxen Sodium Tablets (2 x 220 mg) in the Fasted State

This study is being conducted to investigate the rate and extent of naproxen absorption from the Test naproxen sodium formulation is bioequivalent to Aleve® naproxen sodium, a Reference product currently marketed in The Netherlands in order to support the registration of the Reckitt Benckiser (RB) naproxen sodium (220 mg tablets).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Test; Drug: Reference

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• 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 ≥ 20 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. Intention to become pregnant during the course of the study
3. Lack of safe contraception.
4. A history and/or presence of significant disease of any body system, including psychiatric disorders.
5. Any condition that may currently interfere with the absorption, distribution, metabolism or excretion of drugs.
6. A history of allergy or intolerance related to treatment with naproxen or other NSAIDs, or the excipients of the formulations.
7. A history of or active peptic or duodenal ulcers or gastro-intestinal bleed or upper gastro-intestinal bleed, or other significant gastro-intestinal disorders.
8. A history of frequent dyspepsia, e.g. heartburn or indigestion.
9. A history of migraine.
10. Current smokers and ex-smokers who have smoked or used nicotine replacement products during the previous 6 months prior to first dosing.
11. A history of substance abuse (including alcohol).
12. High consumption of stimulating drinks (coffee, tea, cola, energy drinks etc; total caffeine intake per day above 300 mg [1 cup of coffee equates to approximately 50 mg caffeine]).
13. Those with positive screen/test for drugs of abuse and alcohol.
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 (drug, food or herb) 30 days prior to the first dose of study medication (such as barbiturates, carbamazepine, erythromycin, phenytoin, etc.).
15. Ingestion of an over-the-counter (OTC) preparation within 7 days before the first dose of study medication, including herbal medications, vitamin/fish oil supplements, naproxen and other NSAIDs.
16. Those who have consumed grapefruit or grapefruit juice, pummelo or Seville oranges in the 7 days prior to randomisation.
17. Strenuous physical exercise from 48 hours prior to randomisation to the post study Follow-Up Visit.
18. Donation of blood in quantity > 400 ml or other blood products e.g. to the blood transfusion service or significant loss of blood in the 12 weeks prior to screening.
19. Known human immunodeficiency virus (HIV) positive status, or a positive viral serology screen.
20. Topical use of naproxen within 7 days before the first dose of study medication.
21. Those previously randomised into this study.
22. Those who are an employee at the study site.
23. Those who are a partner or first degree relative of the Investigator.
24. Receipt of an investigational product, or participation in another trial involving a marketed or investigational drug in the 12 weeks prior to screening.
25. 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
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; Treatment Order: Test, Reference	Drug: Test; RB naproxen sodium tablets (2x220mg); Drug: Reference; Aleve naproxen sodium tablets (2x220mg)
EXPERIMENTAL: 2; Treatment Order: Reference, Test	Drug: Test; RB naproxen sodium tablets (2x220mg); Drug: Reference; Aleve naproxen sodium tablets (2x220mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under Plasma Concentration-time at Time t (AUC0-t)	AUC0-t defines Area under the plasma concentration-time curve (AUC) from administration to the last quantifiable concentration at time t.	Pre-dose and at 15 mins, 30 mins, 45 mins, 1 hour, 1 hour 15 mins, 1 hour 30 mins, 1 hour 45 mins, 2 hours, 2 hours 30 mins, 3, 4, 6, 9, 15 (Day 1), 24, 36 (Day 2), 48 (Day 3) and 72 (Day 4) hours post-dose
Maximum Plasma Concentration (Cmax)		Pre-dose and at 15 mins, 30 mins, 45 mins, 1 hour, 1 hour 15 mins, 1 hour 30 mins, 1 hour 45 mins, 2 hours, 2 hours 30 mins, 3, 4, 6, 9, 15 (Day 1), 24, 36 (Day 2), 48 (Day 3) and 72 (Day 4) hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Elimination Rate Constant (Kel)	Elimination Rate Constant (Kel) was calculated as the absolute value of the log-linear regression slope of the elimination phase (logged) over time (linear) using the post Cmax concentrations [at least 3 non-below the limit of quantification (BLQ)] that maximised the adjusted R2.	Pre-dose and at 15 mins, 30 mins, 45 mins, 1 hour, 1 hour 15 mins, 1 hour 30 mins, 1 hour 45 mins, 2 hours, 2 hours 30 mins, 3, 4, 6, 9, 15 (Day 1), 24, 36 (Day 2), 48 (Day 3) and 72 (Day 4) hours post-dose
Area Under the Plasma Concentration Curve From Administration to Infinity (AUC0-inf)	Area under the plasma concentration curve from administration to infinity (AUC0-inf) was calculated as AUC0-t + (Ct/Kel) where Ct was the last quantifiable concentration at time t	Pre-dose and at 15 mins, 30 mins, 45 mins, 1 hour, 1 hour 15 mins, 1 hour 30 mins, 1 hour 45 mins, 2 hours, 2 hours 30 mins, 3, 4, 6, 9, 15 (Day 1), 24, 36 (Day 2), 48 (Day 3) and 72 (Day 4) hours post-dose
Residual Area (AUC%Extrap)	AUC%extrap represents the percentage of the AUC0-inf obtained by extrapolation, calculated as (1 - [AUC0-last/AUC0-inf]) multiplied by 100.	Pre-dose and at 15 mins, 30 mins, 45 mins, 1 hour, 1 hour 15 mins, 1 hour 30 mins, 1 hour 45 mins, 2 hours, 2 hours 30 mins, 3, 4, 6, 9, 15 (Day 1), 24, 36 (Day 2), 48 (Day 3) and 72 (Day 4) hours post-dose
Time Until Cmax is First Achieved (Tmax)		Pre-dose and at 15 mins, 30 mins, 45 mins, 1 hour, 1 hour 15 mins, 1 hour 30 mins, 1 hour 45 mins, 2 hours, 2 hours 30 mins, 3, 4, 6, 9, 15 (Day 1), 24, 36 (Day 2), 48 (Day 3) and 72 (Day 4) hours post-dose
Plasma Concentration (Elimination) Half-life (T1/2)		Pre-dose and at 15 mins, 30 mins, 45 mins, 1 hour, 1 hour 15 mins, 1 hour 30 mins, 1 hour 45 mins, 2 hours, 2 hours 30 mins, 3, 4, 6, 9, 15 (Day 1), 24, 36 (Day 2), 48 (Day 3) and 72 (Day 4) hours post-dose
Plasma Concentration at Each Planned Nominal Time-point (Cn)		Pre-dose and at 15 mins, 30 mins, 45 mins, 1 hour, 1 hour 15 mins, 1 hour 30 mins, 1 hour 45 mins, 2 hours, 2 hours 30 mins, 3, 4, 6, 9, 15 (Day 1), 24, 36 (Day 2), 48 (Day 3) and 72 (Day 4) hours post-dose
Occurrence of Adverse Events (AEs)	Intensity was determined by the Investigator Mild = AE does not limit usual activities; subject may experience slight discomfort. Moderate = AE results in some limitation of usual activities; subject may experience significant discomfort. Severe = AE results in an inability to carry out usual activities; subject may experience intolerable discomfort or pain. Relationship to Investigational Medicinal Products (IMP) Certain = AE was definitely caused by IMP. Probable = Most likely that the AE was caused by IMP. Possible = Reasonable suspicion that the AE was caused by IMP Unlikely = Slight, but remote, chance that the AE was caused by IMP but the balance of judgment is that it was most likely not due to the IMP. Unrelated = No possibility that the AE was caused by IMP Un-assessable/Unclassified = Insufficient information to be able to make an assessment. Conditional/Unclassified = Insufficient information to make an assessment at present.	Up to follow-up day 7

Collaborators and Investigators

• Sponsor: Reckitt Benckiser Healthcare (UK) Limited
• Collaborators: Simbec Research

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 12, 2016
• Primary Completion (ACTUAL): December 2, 2016
• Study Completion (ACTUAL): December 2, 2016

Study Registration Dates

• First Submitted: May 17, 2017
• First Submitted That Met QC Criteria: May 23, 2017
• First Posted (ACTUAL): May 30, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 28, 2019
• Last Update Submitted That Met QC Criteria: February 26, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: RB9-UK-1514

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