HealthyPhase 1NCT03167541

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

A Phase 1 study testing Test and Reference in people with Healthy, run by Reckitt Benckiser Healthcare (UK) Limited.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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… Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Test and Reference
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: No sites listed yet
Study dates: 12 Oct 2016to 2 Dec 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Male or female subjects who have given written informed consent.
Age: ≥ 18 years ≤ 50 years.
Body Mass Index (BMI) of ≥ 20 and ≤ 30 kg/m2.
Healthy as determined by past medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory tests at screening.
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.
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 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.

Who cannot join

Pregnant or lactating females.
Intention to become pregnant during the course of the study
Lack of safe contraception.
A history and/or presence of significant disease of any body system, including psychiatric disorders.
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 naproxen or other NSAIDs, or the excipients of the formulations.

Show all 25Show fewer

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 or used nicotine replacement products during the previous 6 months prior to first dosing.
A history of substance abuse (including alcohol).
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]).
Those with positive screen/test for drugs of abuse and alcohol.
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.).
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.
Those who have consumed grapefruit or grapefruit juice, pummelo or Seville oranges in the 7 days prior to randomisation.
Strenuous physical exercise from 48 hours prior to randomisation to the post study Follow-Up Visit.
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.
Known human immunodeficiency virus (HIV) positive status, or a positive viral serology screen.
Topical use of naproxen within 7 days before the first dose of study medication.
Those previously randomised into this study.
Those who are an employee at the study site.
Those who are a partner or first degree relative of the Investigator.
Receipt of an investigational product, or participation in another trial involving a marketed or investigational drug in the 12 weeks prior to screening.
Those unable in the opinion of the Investigator to comply fully with the study requirements.

About this study

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

Conditions: Healthy
Being tested: Test, Reference

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TestDrug
RB naproxen sodium tablets (2x220mg)
ReferenceDrug
Aleve naproxen sodium tablets (2x220mg)

Study groups in NCT03167541
Study group	Role	What they receive
1	Experimental	Treatment Order: Test, Reference Receives: Drug: Test; Drug: Reference
2	Experimental	Treatment Order: Reference, Test Receives: Drug: Test; Drug: Reference

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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)
Measured: 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 outcomes (7)

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.
Measured: 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
Measured: 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.
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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.
Measured: Up to follow-up day 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Oct 20162 Dec 2016

First posted30 May 2017
Study start12 Oct 2016
Primary completion2 Dec 2016
Study completion2 Dec 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HealthyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03167541
Sponsor's protocol ID: RB9-UK-1514
Status last verified: Feb 2019
First submitted: 17 May 2017
Last updated: 28 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 28 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03167541
Acronym / sponsor ID: RB9-UK-1514
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Reckitt Benckiser Healthcare (UK) LimitedIndustry (pharma, biotech, devices)
Collaborators: Simbec Research
Study start: 12 Oct 2016 (actual)
Primary completion: 2 Dec 2016 (actual)
Study completion: 2 Dec 2016 (actual)
First posted: 30 May 2017 (actual)
Results: Posted 28 Feb 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: Test, Drug: ReferenceTreatment Order: Test, Reference
2	Experimental	Drug: Test, Drug: ReferenceTreatment Order: Reference, Test

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Male or female subjects who have given written informed consent.
Age: ≥ 18 years ≤ 50 years.
Body Mass Index (BMI) of ≥ 20 and ≤ 30 kg/m2.
Healthy as determined by past medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory tests at screening.
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.

Key exclusion criteria (25 listed)

Pregnant or lactating females.
Intention to become pregnant during the course of the study
Lack of safe contraception.
A history and/or presence of significant disease of any body system, including psychiatric disorders.
Any condition that may currently interfere with the absorption, distribution, metabolism or excretion of drugs.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TestRB naproxen sodium tablets (2x220mg)	Drug	1, 2
ReferenceAleve naproxen sodium tablets (2x220mg)	Drug	1, 2

Primary outcome

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

7 secondary outcomes

Elimination Rate Constant (Kel)
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
Area Under the Plasma Concentration Curve From Administration to Infinity (AUC0-inf)
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
Residual Area (AUC%Extrap)
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
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
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
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
Occurrence of Adverse Events (AEs)
Time frame: Up to follow-up day 7

Results and safety

Results posted to the registry on 28 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
RB Naproxen (Test) First, Then Aleve Naproxen (Reference)	9	9
Aleve Naproxen (Reference) First, Then RB Naproxen (Test)	9	9

Primary outcome: Area Under Plasma Concentration-time at Time t (AUC0-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. Mean (Standard Deviation). Unit: h*μg/mL

Measure	Test: RB Naproxen Sodium 2 x 220 mg n = 18	Reference: Aleve Naproxen Sodium 2x220 mg n = 18
Value	915 (207)	909 (186)

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

Primary outcome: Maximum Plasma Concentration (Cmax)

Measure	Test: RB Naproxen Sodium 2 x 220 mg n = 18	Reference: Aleve Naproxen Sodium 2x220 mg n = 18
Value	66.9 (11.9)	65.2 (9.65)

Population analysed: PK Parameter Summary Set Population

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to follow-up day 7. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Test: RB Naproxen Sodium 2 x 220 mg	0 of 18 (0%)	1 of 18 (5.6%)	0 of 18
Reference: Aleve® Naproxen Sodium 2 x 220 mg	0 of 18 (0%)	0 of 18 (0%)	0 of 18

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Robert Adams, MBBS principal investigator

Simbec Research

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Test and Reference in people with Healthy, run by Reckitt Benckiser Healthcare (UK) Limited.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under Plasma Concentration-time at Time t (AUC0-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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03167541.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2019.