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

• Sponsor: Reckitt Benckiser Healthcare (UK) Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03167541
• Collaborator: Simbec Research (Industry)
• Enrollment: 18
• Arms: 2
• Actual Duration (Months): 1.7

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Test; Drug: Reference	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: Oct 12, 2016
• Actual Primary Completion Date: Dec 2, 2016
• Actual Study Completion Date: Dec 2, 2016

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

1. Area Under Plasma Concentration-time at Time t (AUC0-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]

   AUC0-t defines Area under the plasma concentration-time curve (AUC) from administration to the last quantifiable concentration at time t.

2. 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

1. Elimination Rate Constant (Kel) [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]

   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.

2. Area Under the Plasma Concentration Curve From Administration to Infinity (AUC0-inf) [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) was calculated as AUC0-t + (Ct/Kel) where Ct was the last quantifiable concentration at time t

3. Residual Area (AUC%Extrap) [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]

   AUC%extrap represents the percentage of the AUC0-inf obtained by extrapolation, calculated as (1 - [AUC0-last/AUC0-inf]) multiplied by 100.

4. 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]

5. 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]

6. 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]

7. Occurrence of Adverse Events (AEs) [Up to follow-up day 7]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Reckitt Benckiser Healthcare (UK) Limited
• Simbec Research

Investigators

• Principal Investigator: Robert Adams, MBBS, Simbec Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Reckitt Benckiser Healthcare (UK) Limited
• ClinicalTrials.gov Identifier: NCT03167541
• Other Study ID Numbers: RB9-UK-1514
• First Posted: May 30, 2017
• Last Update Posted: Feb 28, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

Participant Flow

Recruitment Details	This was a single-centre study conducted in United Kingdom.
Pre-assignment Detail	Total 32 subjects were screened. Of these, 6 subjects were screen failures, 2 were surplus to requirement, 6 were reserve subjects. Subjects randomized were 18.

Arm/Group Title	RB Naproxen (Test) First, Then Aleve Naproxen (Reference)	Aleve Naproxen (Reference) First, Then RB Naproxen (Test)
Arm/Group Description	Participants first received RB naproxen sodium 2 x 220 mg tablets single-oral dose in a fasting condition. After a washout period of 5-8 Days, they then received Aleve naproxen sodium 2 x 220 mg tablets single-oral dose in a fasting condition.	Participants first received Aleve naproxen sodium 2 x 220 mg tablets single-oral dose in a fasting condition. After a washout period of 5-8 Days, they then received RB naproxen sodium 2 x 220 mg tablets single-oral dose in a fasting condition.
Period Title: First Intervention
STARTED	9	9
COMPLETED	9	9
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	9	9
COMPLETED	9	9
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	9	9
COMPLETED	9	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	RB Naproxen Sodium 2 x 220 mg single dose by mouth under fasted condition. Aleve® Naproxen Sodium 2 x 220 mg single dose by mouth under fasted condition. There was a 5 to 8 days washout period between each administration.
Overall Participants	18
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	18 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.6 (9.55)
Sex: Female, Male (Count of Participants)
Female	7 38.9%
Male	11 61.1%
Race/Ethnicity, Customized (participants) [Number]
White	18 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	172 (11.77)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	74.69 (14.676)
Body Mass Index (BMI) (kg/m²) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m²]	25.025 (2.7857)

Outcome Measures

1. Primary Outcome

Title	Area Under Plasma Concentration-time at Time t (AUC0-t)
Description	AUC0-t defines Area under the plasma concentration-time curve (AUC) from administration to the last quantifiable concentration at time t.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Parameter Summary Set Population includes all subjects from the PK dataset with evaluable PK parameters for each treatment period.

Arm/Group Title	Test: RB Naproxen Sodium 2 x 220 mg	Reference: Aleve Naproxen Sodium 2x220 mg
Arm/Group Description	RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition	Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
Measure Participants	18	18
Mean (Standard Deviation) [h*μg/mL]	915 (207)	909 (186)

2. Primary Outcome

Title	Maximum Plasma Concentration (Cmax)
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Parameter Summary Set Population

Arm/Group Title	Test: RB Naproxen Sodium 2 x 220 mg	Reference: Aleve Naproxen Sodium 2x220 mg
Arm/Group Description	RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition	Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
Measure Participants	18	18
Mean (Standard Deviation) [μg/mL]	66.9 (11.9)	65.2 (9.65)

3. Secondary Outcome

Title	Elimination Rate Constant (Kel)
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Parameter Summary Set Population

Arm/Group Title	Test: RB Naproxen Sodium 2 x 220 mg	Reference: Aleve Naproxen Sodium 2x220 mg
Arm/Group Description	RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition	Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
Measure Participants	18	18
Mean (Standard Deviation) [1/h]	0.0413 (0.00858)	0.0414 (0.00673)

4. Secondary Outcome

Title	Area Under the Plasma Concentration Curve From Administration to Infinity (AUC0-inf)
Description	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
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Parameter Summary Set Population

Arm/Group Title	Test: RB Naproxen Sodium 2 x 220 mg	Reference: Aleve Naproxen Sodium 2x220 mg
Arm/Group Description	RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition	Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
Measure Participants	18	18
Mean (Standard Deviation) [h*μg/mL]	972 (232)	963 (203)

5. Secondary Outcome

Title	Residual Area (AUC%Extrap)
Description	AUC%extrap represents the percentage of the AUC0-inf obtained by extrapolation, calculated as (1 - [AUC0-last/AUC0-inf]) multiplied by 100.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Parameter Summary Set population

Arm/Group Title	Test: RB Naproxen Sodium 2 x 220 mg	Reference: Aleve Naproxen Sodium 2x220 mg
Arm/Group Description	RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition	Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
Measure Participants	18	18
Mean (Standard Deviation) [Percentage of AUC]	5.68 (2.03)	5.58 (1.72)

6. Secondary Outcome

Title	Time Until Cmax is First Achieved (Tmax)
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Parameter Summary Set population

Arm/Group Title	Test: RB Naproxen Sodium 2 x 220 mg	Reference: Aleve Naproxen Sodium 2x220 mg
Arm/Group Description	RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition	Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
Measure Participants	18	18
Mean (Standard Deviation) [hour]	1.38 (1.35)	1.31 (1.28)

7. Secondary Outcome

Title	Plasma Concentration (Elimination) Half-life (T1/2)
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Parameter Summary Set population

Arm/Group Title	Test: RB Naproxen Sodium 2 x 220 mg	Reference: Aleve Naproxen Sodium 2x220 mg
Arm/Group Description	RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition	Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
Measure Participants	18	18
Mean (Standard Deviation) [hour]	17.3 (2.92)	17.1 (2.48)

8. Secondary Outcome

Title	Plasma Concentration at Each Planned Nominal Time-point (Cn)
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Parameter Summary Set population

Arm/Group Title	Test: RB Naproxen Sodium 2 x 220 mg	Reference: Aleve Naproxen Sodium 2x220 mg
Arm/Group Description	RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition	Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
Measure Participants	18	18
Pre-dose	0 (0)	0 (0)
15 mins	15.6 (14.8)	16.1 (12)
30 mins	49 (22.7)	47.3 (23.3)
45 mins	58.4 (20)	54.1 (22.4)
1 hr	57 (13.1)	53.6 (18.7)
1 hr 15 mins	53.6 (10.4)	52.9 (15.8)
1 hr 30 mins	55.9 (10.1)	52.5 (14.2)
1 hr 45 mins	52.5 (8.54)	54 (10.2)
2 hrs	51.4 (8.05)	53.4 (9.13)
2 hrs 30 mins	48.3 (7.17)	50 (8.47)
3 hrs	45 (6.34)	47.1 (7.03)
4 hrs	40.8 (6)	41.8 (6.36)
6 hrs	34.1 (6.34)	34.6 (6.22)
9 hrs	6.34 (5.21)	27.7 (5.25)
15 hrs	4.42 (23.5)	18.9 (3.68)
24 hrs	3.61 (26.1)	13.3 (3.08)
36 hrs	2.8 (35)	7.9 (2.53)
48 hrs	1.98 (39)	4.98 (1.89)
72 hrs	0.938 (42.3)	2.15 (0.764)

9. Secondary Outcome

Title	Occurrence of Adverse Events (AEs)
Description	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.
Time Frame	Up to follow-up day 7

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Test: RB Naproxen Sodium 2 x 220 mg	Reference: Aleve® Naproxen Sodium 2 x 220 mg
Arm/Group Description	RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition	Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
Measure Participants	18	18
Treatment Emergent Adverse Event (TEAE)	1	0
Serious TEAE	0	0
TEAE Leading to Withdrawal	0	0
AE of mild intensity	1	0
AE of moderate intensity	0	0
AE of severe intensity	0	0
Certain related AE	0	0
Probable related AE	0	0
Possible related AE	0	0
Unlikely related AE	1	0
Unrelated related AE	0	0
Conditional/Unclassified related AE	0	0
Unassessable/Unclassifiable related AE	0	0

Adverse Events

Time Frame	Up to follow-up day 7
Adverse Event Reporting Description	Treatment-emergent adverse events (TEAEs), i.e., existing conditions that worsened or events that occurred during the course of the study after first administration of IMP and before the end of the study, are included.
Arm/Group Title	Test: RB Naproxen Sodium 2 x 220 mg		Reference: Aleve® Naproxen Sodium 2 x 220 mg
Arm/Group Description	RB Naproxen Sodium 2 x 220 mg single dose by mouth under fasted condition.		Aleve Naproxen Sodium 2 x 220 mg single dose by mouth under fasted condition.
All Cause Mortality
	Test: RB Naproxen Sodium 2 x 220 mg		Reference: Aleve® Naproxen Sodium 2 x 220 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)
Serious Adverse Events
	Test: RB Naproxen Sodium 2 x 220 mg		Reference: Aleve® Naproxen Sodium 2 x 220 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Test: RB Naproxen Sodium 2 x 220 mg		Reference: Aleve® Naproxen Sodium 2 x 220 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/18 (5.6%)		0/18 (0%)
Gastrointestinal disorders
Dyspepsia	1/18 (5.6%)	1	0/18 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.