Trial Outcomes & Findings for Naproxen Sodium (2 x 220 mg) Fasted Comparative Bioavailability Study (NCT NCT03167541)
NCT ID: NCT03167541
Last Updated: 2019-02-28
Results Overview
AUC0-t defines Area under the plasma concentration-time curve (AUC) from administration to the last quantifiable concentration at time t.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
18 participants
Primary outcome timeframe
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
Results posted on
2019-02-28
Participant Flow
This was a single-centre study conducted in United Kingdom.
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.
Participant milestones
| Measure |
RB Naproxen (Test) First, Then Aleve Naproxen (Reference)
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.
|
Aleve Naproxen (Reference) First, Then RB Naproxen (Test)
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.
|
|---|---|---|
|
First Intervention
STARTED
|
9
|
9
|
|
First Intervention
COMPLETED
|
9
|
9
|
|
First Intervention
NOT COMPLETED
|
0
|
0
|
|
Washout: 5-8 Days
STARTED
|
9
|
9
|
|
Washout: 5-8 Days
COMPLETED
|
9
|
9
|
|
Washout: 5-8 Days
NOT COMPLETED
|
0
|
0
|
|
Second Intervention
STARTED
|
9
|
9
|
|
Second Intervention
COMPLETED
|
9
|
9
|
|
Second Intervention
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Naproxen Sodium (2 x 220 mg) Fasted Comparative Bioavailability Study
Baseline characteristics by cohort
| Measure |
All Study Participants
n=18 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.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
18 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
33.6 years
STANDARD_DEVIATION 9.55 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
18 participants
n=5 Participants
|
|
Height
|
172 cm
STANDARD_DEVIATION 11.77 • n=5 Participants
|
|
Weight
|
74.69 kg
STANDARD_DEVIATION 14.676 • n=5 Participants
|
|
Body Mass Index (BMI)
|
25.025 kg/m²
STANDARD_DEVIATION 2.7857 • n=5 Participants
|
PRIMARY outcome
Timeframe: 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-dosePopulation: Pharmacokinetic (PK) Parameter Summary Set Population includes all subjects from the PK dataset with evaluable PK parameters for each treatment period.
AUC0-t defines Area under the plasma concentration-time curve (AUC) from administration to the last quantifiable concentration at time t.
Outcome measures
| Measure |
Test: RB Naproxen Sodium 2 x 220 mg
n=18 Participants
RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition
|
Reference: Aleve Naproxen Sodium 2x220 mg
n=18 Participants
Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
|
|---|---|---|
|
Area Under Plasma Concentration-time at Time t (AUC0-t)
|
915 h*μg/mL
Standard Deviation 207
|
909 h*μg/mL
Standard Deviation 186
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Parameter Summary Set Population
Outcome measures
| Measure |
Test: RB Naproxen Sodium 2 x 220 mg
n=18 Participants
RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition
|
Reference: Aleve Naproxen Sodium 2x220 mg
n=18 Participants
Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
66.9 μg/mL
Standard Deviation 11.9
|
65.2 μg/mL
Standard Deviation 9.65
|
SECONDARY outcome
Timeframe: 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-dosePopulation: PK Parameter Summary Set Population
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.
Outcome measures
| Measure |
Test: RB Naproxen Sodium 2 x 220 mg
n=18 Participants
RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition
|
Reference: Aleve Naproxen Sodium 2x220 mg
n=18 Participants
Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
|
|---|---|---|
|
Elimination Rate Constant (Kel)
|
0.0413 1/h
Standard Deviation 0.00858
|
0.0414 1/h
Standard Deviation 0.00673
|
SECONDARY outcome
Timeframe: 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-dosePopulation: PK Parameter Summary Set Population
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
Outcome measures
| Measure |
Test: RB Naproxen Sodium 2 x 220 mg
n=18 Participants
RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition
|
Reference: Aleve Naproxen Sodium 2x220 mg
n=18 Participants
Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
|
|---|---|---|
|
Area Under the Plasma Concentration Curve From Administration to Infinity (AUC0-inf)
|
972 h*μg/mL
Standard Deviation 232
|
963 h*μg/mL
Standard Deviation 203
|
SECONDARY outcome
Timeframe: 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-dosePopulation: PK Parameter Summary Set population
AUC%extrap represents the percentage of the AUC0-inf obtained by extrapolation, calculated as (1 - \[AUC0-last/AUC0-inf\]) multiplied by 100.
Outcome measures
| Measure |
Test: RB Naproxen Sodium 2 x 220 mg
n=18 Participants
RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition
|
Reference: Aleve Naproxen Sodium 2x220 mg
n=18 Participants
Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
|
|---|---|---|
|
Residual Area (AUC%Extrap)
|
5.68 Percentage of AUC
Standard Deviation 2.03
|
5.58 Percentage of AUC
Standard Deviation 1.72
|
SECONDARY outcome
Timeframe: 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-dosePopulation: PK Parameter Summary Set population
Outcome measures
| Measure |
Test: RB Naproxen Sodium 2 x 220 mg
n=18 Participants
RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition
|
Reference: Aleve Naproxen Sodium 2x220 mg
n=18 Participants
Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
|
|---|---|---|
|
Time Until Cmax is First Achieved (Tmax)
|
1.38 hour
Standard Deviation 1.35
|
1.31 hour
Standard Deviation 1.28
|
SECONDARY outcome
Timeframe: 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-dosePopulation: PK Parameter Summary Set population
Outcome measures
| Measure |
Test: RB Naproxen Sodium 2 x 220 mg
n=18 Participants
RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition
|
Reference: Aleve Naproxen Sodium 2x220 mg
n=18 Participants
Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
|
|---|---|---|
|
Plasma Concentration (Elimination) Half-life (T1/2)
|
17.3 hour
Standard Deviation 2.92
|
17.1 hour
Standard Deviation 2.48
|
SECONDARY outcome
Timeframe: 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-dosePopulation: PK Parameter Summary Set population
Outcome measures
| Measure |
Test: RB Naproxen Sodium 2 x 220 mg
n=18 Participants
RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition
|
Reference: Aleve Naproxen Sodium 2x220 mg
n=18 Participants
Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
|
|---|---|---|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
Pre-dose
|
0 μg/mL
Standard Deviation 0
|
0 μg/mL
Standard Deviation 0
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
15 mins
|
15.6 μg/mL
Standard Deviation 14.8
|
16.1 μg/mL
Standard Deviation 12
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
30 mins
|
49 μg/mL
Standard Deviation 22.7
|
47.3 μg/mL
Standard Deviation 23.3
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
45 mins
|
58.4 μg/mL
Standard Deviation 20
|
54.1 μg/mL
Standard Deviation 22.4
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
1 hr
|
57 μg/mL
Standard Deviation 13.1
|
53.6 μg/mL
Standard Deviation 18.7
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
1 hr 15 mins
|
53.6 μg/mL
Standard Deviation 10.4
|
52.9 μg/mL
Standard Deviation 15.8
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
1 hr 30 mins
|
55.9 μg/mL
Standard Deviation 10.1
|
52.5 μg/mL
Standard Deviation 14.2
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
1 hr 45 mins
|
52.5 μg/mL
Standard Deviation 8.54
|
54 μg/mL
Standard Deviation 10.2
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
2 hrs
|
51.4 μg/mL
Standard Deviation 8.05
|
53.4 μg/mL
Standard Deviation 9.13
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
2 hrs 30 mins
|
48.3 μg/mL
Standard Deviation 7.17
|
50 μg/mL
Standard Deviation 8.47
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
3 hrs
|
45 μg/mL
Standard Deviation 6.34
|
47.1 μg/mL
Standard Deviation 7.03
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
4 hrs
|
40.8 μg/mL
Standard Deviation 6
|
41.8 μg/mL
Standard Deviation 6.36
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
6 hrs
|
34.1 μg/mL
Standard Deviation 6.34
|
34.6 μg/mL
Standard Deviation 6.22
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
9 hrs
|
6.34 μg/mL
Standard Deviation 5.21
|
27.7 μg/mL
Standard Deviation 5.25
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
15 hrs
|
4.42 μg/mL
Standard Deviation 23.5
|
18.9 μg/mL
Standard Deviation 3.68
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
24 hrs
|
3.61 μg/mL
Standard Deviation 26.1
|
13.3 μg/mL
Standard Deviation 3.08
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
36 hrs
|
2.8 μg/mL
Standard Deviation 35
|
7.9 μg/mL
Standard Deviation 2.53
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
48 hrs
|
1.98 μg/mL
Standard Deviation 39
|
4.98 μg/mL
Standard Deviation 1.89
|
|
Plasma Concentration at Each Planned Nominal Time-point (Cn)
72 hrs
|
0.938 μg/mL
Standard Deviation 42.3
|
2.15 μg/mL
Standard Deviation 0.764
|
SECONDARY outcome
Timeframe: Up to follow-up day 7Population: Safety population
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.
Outcome measures
| Measure |
Test: RB Naproxen Sodium 2 x 220 mg
n=18 Participants
RB naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition
|
Reference: Aleve Naproxen Sodium 2x220 mg
n=18 Participants
Aleve naproxen sodium 2 x 220 mg tablets single dose by mouth under fasted condition.
|
|---|---|---|
|
Occurrence of Adverse Events (AEs)
Treatment Emergent Adverse Event (TEAE)
|
1 Number of events
|
0 Number of events
|
|
Occurrence of Adverse Events (AEs)
Serious TEAE
|
0 Number of events
|
0 Number of events
|
|
Occurrence of Adverse Events (AEs)
TEAE Leading to Withdrawal
|
0 Number of events
|
0 Number of events
|
|
Occurrence of Adverse Events (AEs)
AE of mild intensity
|
1 Number of events
|
0 Number of events
|
|
Occurrence of Adverse Events (AEs)
AE of moderate intensity
|
0 Number of events
|
0 Number of events
|
|
Occurrence of Adverse Events (AEs)
AE of severe intensity
|
0 Number of events
|
0 Number of events
|
|
Occurrence of Adverse Events (AEs)
Certain related AE
|
0 Number of events
|
0 Number of events
|
|
Occurrence of Adverse Events (AEs)
Probable related AE
|
0 Number of events
|
0 Number of events
|
|
Occurrence of Adverse Events (AEs)
Possible related AE
|
0 Number of events
|
0 Number of events
|
|
Occurrence of Adverse Events (AEs)
Unlikely related AE
|
1 Number of events
|
0 Number of events
|
|
Occurrence of Adverse Events (AEs)
Unrelated related AE
|
0 Number of events
|
0 Number of events
|
|
Occurrence of Adverse Events (AEs)
Conditional/Unclassified related AE
|
0 Number of events
|
0 Number of events
|
|
Occurrence of Adverse Events (AEs)
Unassessable/Unclassifiable related AE
|
0 Number of events
|
0 Number of events
|
Adverse Events
Test: RB Naproxen Sodium 2 x 220 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Reference: Aleve® Naproxen Sodium 2 x 220 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Test: RB Naproxen Sodium 2 x 220 mg
n=18 participants at risk
RB Naproxen Sodium 2 x 220 mg single dose by mouth under fasted condition.
|
Reference: Aleve® Naproxen Sodium 2 x 220 mg
n=18 participants at risk
Aleve Naproxen Sodium 2 x 220 mg single dose by mouth under fasted condition.
|
|---|---|---|
|
Gastrointestinal disorders
Dyspepsia
|
5.6%
1/18 • Number of events 1 • Up to follow-up day 7
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.
|
0.00%
0/18 • Up to follow-up day 7
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.
|
Additional Information
Clinical Research Director, Clinical Research
Reckitt Benckiser Healthcare (UK) Ltd
Phone: +44 (0) 1482326151
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place