Healthy
Conditions
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).
Interventions
DRUGTest
RB naproxen sodium tablets (2x220mg)
DRUGReference
Aleve naproxen sodium tablets (2x220mg)
Sponsors
Simbec Research
Reckitt Benckiser Healthcare (UK) Limited
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 | — |
| 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. |
| 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) | 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. |
| 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 | — |
| 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 |
Participant flow
Recruitment details
This was a single-centre study conducted in United Kingdom.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants 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. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 33.6 years STANDARD_DEVIATION 9.55 |
| Body Mass Index (BMI) | 25.025 kg/m² STANDARD_DEVIATION 2.7857 |
| Height | 172 cm STANDARD_DEVIATION 11.77 |
| Race/Ethnicity, Customized White | 18 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 11 Participants |
| Weight | 74.69 kg STANDARD_DEVIATION 14.676 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 1 / 18 | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
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.
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
Population: Pharmacokinetic (PK) Parameter Summary Set Population includes all subjects from the PK dataset with evaluable PK parameters for each treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test: RB Naproxen Sodium 2 x 220 mg | Area Under Plasma Concentration-time at Time t (AUC0-t) | 915 h*μg/mL | Standard Deviation 207 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Area Under Plasma Concentration-time at Time t (AUC0-t) | 909 h*μg/mL | Standard Deviation 186 |
Primary
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
Population: PK Parameter Summary Set Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test: RB Naproxen Sodium 2 x 220 mg | Maximum Plasma Concentration (Cmax) | 66.9 μg/mL | Standard Deviation 11.9 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Maximum Plasma Concentration (Cmax) | 65.2 μg/mL | Standard Deviation 9.65 |
Secondary
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
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
Population: PK Parameter Summary Set Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test: RB Naproxen Sodium 2 x 220 mg | Area Under the Plasma Concentration Curve From Administration to Infinity (AUC0-inf) | 972 h*μg/mL | Standard Deviation 232 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Area Under the Plasma Concentration Curve From Administration to Infinity (AUC0-inf) | 963 h*μg/mL | Standard Deviation 203 |
Secondary
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.
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
Population: PK Parameter Summary Set Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test: RB Naproxen Sodium 2 x 220 mg | Elimination Rate Constant (Kel) | 0.0413 1/h | Standard Deviation 0.00858 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Elimination Rate Constant (Kel) | 0.0414 1/h | Standard Deviation 0.00673 |
Secondary
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.
Time frame: Up to follow-up day 7
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Test: RB Naproxen Sodium 2 x 220 mg | Occurrence of Adverse Events (AEs) | AE of severe intensity | 0 Number of events |
| Test: RB Naproxen Sodium 2 x 220 mg | Occurrence of Adverse Events (AEs) | Serious TEAE | 0 Number of events |
| Test: RB Naproxen Sodium 2 x 220 mg | Occurrence of Adverse Events (AEs) | TEAE Leading to Withdrawal | 0 Number of events |
| Test: RB Naproxen Sodium 2 x 220 mg | Occurrence of Adverse Events (AEs) | AE of mild intensity | 1 Number of events |
| Test: RB Naproxen Sodium 2 x 220 mg | Occurrence of Adverse Events (AEs) | AE of moderate intensity | 0 Number of events |
| Test: RB Naproxen Sodium 2 x 220 mg | Occurrence of Adverse Events (AEs) | Certain related AE | 0 Number of events |
| Test: RB Naproxen Sodium 2 x 220 mg | Occurrence of Adverse Events (AEs) | Probable related AE | 0 Number of events |
| Test: RB Naproxen Sodium 2 x 220 mg | Occurrence of Adverse Events (AEs) | Possible related AE | 0 Number of events |
| Test: RB Naproxen Sodium 2 x 220 mg | Occurrence of Adverse Events (AEs) | Unlikely related AE | 1 Number of events |
| Test: RB Naproxen Sodium 2 x 220 mg | Occurrence of Adverse Events (AEs) | Unrelated related AE | 0 Number of events |
| Test: RB Naproxen Sodium 2 x 220 mg | Occurrence of Adverse Events (AEs) | Conditional/Unclassified related AE | 0 Number of events |
| Test: RB Naproxen Sodium 2 x 220 mg | Occurrence of Adverse Events (AEs) | Unassessable/Unclassifiable related AE | 0 Number of events |
| Test: RB Naproxen Sodium 2 x 220 mg | Occurrence of Adverse Events (AEs) | Treatment Emergent Adverse Event (TEAE) | 1 Number of events |
| Reference: Aleve Naproxen Sodium 2x220 mg | Occurrence of Adverse Events (AEs) | Conditional/Unclassified related AE | 0 Number of events |
| Reference: Aleve Naproxen Sodium 2x220 mg | Occurrence of Adverse Events (AEs) | Treatment Emergent Adverse Event (TEAE) | 0 Number of events |
| Reference: Aleve Naproxen Sodium 2x220 mg | Occurrence of Adverse Events (AEs) | Probable related AE | 0 Number of events |
| Reference: Aleve Naproxen Sodium 2x220 mg | Occurrence of Adverse Events (AEs) | Serious TEAE | 0 Number of events |
| Reference: Aleve Naproxen Sodium 2x220 mg | Occurrence of Adverse Events (AEs) | Unrelated related AE | 0 Number of events |
| Reference: Aleve Naproxen Sodium 2x220 mg | Occurrence of Adverse Events (AEs) | TEAE Leading to Withdrawal | 0 Number of events |
| Reference: Aleve Naproxen Sodium 2x220 mg | Occurrence of Adverse Events (AEs) | Possible related AE | 0 Number of events |
| Reference: Aleve Naproxen Sodium 2x220 mg | Occurrence of Adverse Events (AEs) | AE of mild intensity | 0 Number of events |
| Reference: Aleve Naproxen Sodium 2x220 mg | Occurrence of Adverse Events (AEs) | Unassessable/Unclassifiable related AE | 0 Number of events |
| Reference: Aleve Naproxen Sodium 2x220 mg | Occurrence of Adverse Events (AEs) | AE of moderate intensity | 0 Number of events |
| Reference: Aleve Naproxen Sodium 2x220 mg | Occurrence of Adverse Events (AEs) | AE of severe intensity | 0 Number of events |
| Reference: Aleve Naproxen Sodium 2x220 mg | Occurrence of Adverse Events (AEs) | Unlikely related AE | 0 Number of events |
| Reference: Aleve Naproxen Sodium 2x220 mg | Occurrence of Adverse Events (AEs) | Certain related AE | 0 Number of events |
Secondary
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
Population: PK Parameter Summary Set population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 1 hr 15 mins | 53.6 μg/mL | Standard Deviation 10.4 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 3 hrs | 45 μg/mL | Standard Deviation 6.34 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 45 mins | 58.4 μg/mL | Standard Deviation 20 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 4 hrs | 40.8 μg/mL | Standard Deviation 6 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 1 hr 30 mins | 55.9 μg/mL | Standard Deviation 10.1 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 6 hrs | 34.1 μg/mL | Standard Deviation 6.34 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 30 mins | 49 μg/mL | Standard Deviation 22.7 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 9 hrs | 6.34 μg/mL | Standard Deviation 5.21 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 1 hr 45 mins | 52.5 μg/mL | Standard Deviation 8.54 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 15 hrs | 4.42 μg/mL | Standard Deviation 23.5 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 1 hr | 57 μg/mL | Standard Deviation 13.1 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 24 hrs | 3.61 μg/mL | Standard Deviation 26.1 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 2 hrs | 51.4 μg/mL | Standard Deviation 8.05 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 36 hrs | 2.8 μg/mL | Standard Deviation 35 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 48 hrs | 1.98 μg/mL | Standard Deviation 39 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 15 mins | 15.6 μg/mL | Standard Deviation 14.8 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 72 hrs | 0.938 μg/mL | Standard Deviation 42.3 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 2 hrs 30 mins | 48.3 μg/mL | Standard Deviation 7.17 |
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Pre-dose | 0 μg/mL | Standard Deviation 0 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 36 hrs | 7.9 μg/mL | Standard Deviation 2.53 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Pre-dose | 0 μg/mL | Standard Deviation 0 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 15 mins | 16.1 μg/mL | Standard Deviation 12 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 30 mins | 47.3 μg/mL | Standard Deviation 23.3 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 45 mins | 54.1 μg/mL | Standard Deviation 22.4 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 1 hr | 53.6 μg/mL | Standard Deviation 18.7 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 1 hr 15 mins | 52.9 μg/mL | Standard Deviation 15.8 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 1 hr 30 mins | 52.5 μg/mL | Standard Deviation 14.2 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 1 hr 45 mins | 54 μg/mL | Standard Deviation 10.2 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 2 hrs | 53.4 μg/mL | Standard Deviation 9.13 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 2 hrs 30 mins | 50 μg/mL | Standard Deviation 8.47 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 3 hrs | 47.1 μg/mL | Standard Deviation 7.03 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 4 hrs | 41.8 μg/mL | Standard Deviation 6.36 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 6 hrs | 34.6 μg/mL | Standard Deviation 6.22 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 9 hrs | 27.7 μg/mL | Standard Deviation 5.25 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 15 hrs | 18.9 μg/mL | Standard Deviation 3.68 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 24 hrs | 13.3 μg/mL | Standard Deviation 3.08 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 48 hrs | 4.98 μg/mL | Standard Deviation 1.89 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration at Each Planned Nominal Time-point (Cn) | 72 hrs | 2.15 μg/mL | Standard Deviation 0.764 |
Secondary
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
Population: PK Parameter Summary Set population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test: RB Naproxen Sodium 2 x 220 mg | Plasma Concentration (Elimination) Half-life (T1/2) | 17.3 hour | Standard Deviation 2.92 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Plasma Concentration (Elimination) Half-life (T1/2) | 17.1 hour | Standard Deviation 2.48 |
Secondary
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.
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
Population: PK Parameter Summary Set population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test: RB Naproxen Sodium 2 x 220 mg | Residual Area (AUC%Extrap) | 5.68 Percentage of AUC | Standard Deviation 2.03 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Residual Area (AUC%Extrap) | 5.58 Percentage of AUC | Standard Deviation 1.72 |
Secondary
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
Population: PK Parameter Summary Set population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test: RB Naproxen Sodium 2 x 220 mg | Time Until Cmax is First Achieved (Tmax) | 1.38 hour | Standard Deviation 1.35 |
| Reference: Aleve Naproxen Sodium 2x220 mg | Time Until Cmax is First Achieved (Tmax) | 1.31 hour | Standard Deviation 1.28 |