Healthy Volunteer Study
Conditions
Keywords
Ibuprofen
Brief summary
The purpose of this study was to determine the rate and extent of absorption of Ibuprofen suspension formulations.
Interventions
DRUGAlgifor Dolo Junior®
Sponsors
Reckitt Benckiser Healthcare (UK) Limited
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who have given written informed consent. * Age: ≥18 years ≤50 years. * Sex: Male or female subjects are eligible for entry. * Female subject of child bearing potential with a negative pregnancy test at the screening visit and willing to use an effective method of contraception, * 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 * Status: Healthy subjects as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening. * Healthy Subjects with a Body Mass Index (BMI) of ≥20 and ≤27 kg/m2
Exclusion criteria
* Pregnancy or lactating female subjects. * A history of significant disease of any body system. * 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 ibuprofen, aspirin or other Non-Steroidal Anti-inflammatory Drug,or the excipients of the formulations. * 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 within 6 months. * A history of drug abuse (including alcohol). * High consumption of stimulating drinks (caffeine intake per day above 300 mg). * Those with positive drugs of abuse screen including alcohol on any occasion throughout the study. * Ingestion of a prescribed drug at any time in the 14 days before dosing with study medication (excluding hormonal contraceptives and hormone replacement therapy), or consumption of enzyme inhibitors or inducers during the previous month (such as barbiturates, carbamazepine, erythromycin, phenytoin, etc.). * Ingestion of an over-the-counter preparation within 7 days before dosing with study medication. * Donation of blood in quantity in the previous 12 weeks before enrolment into the study. * Known human immune deficiency virus (HIV) positive status, or a positive viral serology screen. * Topical use of ibuprofen within 7 days before dosing with study medication. * Those previously randomised into this study. * Employee at study site. * Partner or first degree relative of the Investigator. * Those who have participated in a clinical trial in the previous 12 weeks. * Those unable in the opinion of the Investigator to comply fully with the study requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Plasma Concentration (Cmax) | Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose) |
| Area Under the Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t) | Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of AUC0-t/AUC0-inf (AUCR) | Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose) | — |
| Time to Cmax (Tmax) | Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose) | — |
| Elimination Rate Constant (Kel) | Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose) | — |
| Plasma Concentration at Each Planned Nominal Time-point (Cn) | Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose) | Cn was derived using linear interpolation from the 2 samples taken either side of the nominal time where there was a sampling time deviation. For concentrations that were missing due to blood samples not being taken Cn was not derived. |
| Number of Subjects With Adverse Events (AEs). | Up to follow-up day 7 | Intensity was determined by the Investigator. For symptomatic AEs the following definitions were applied. Mild = AE did not limit usual activities; subject may have experienced slight discomfort. Moderate = AE resulted in some limitation of usual activities; subject may have experienced significant discomfort. Severe = AE resulted in an inability to carry out usual activities; subject may have experienced intolerable discomfort/pain. Relationship to Investigational Medicinal Products (IMP) Unassessable/Unclassified = Insufficient information to be able to make an assessment. Conditional/ Unclassified = Insufficient information to make an assessment at present. Unrelated = No possibility that AE was caused by IMP. Unlikely = Slight, but remote, chance that AE was caused by IMP. Possible = Reasonable suspicion that the AE was caused by IMP. Probable = Most likely that AE was caused by IMP. Certain = AE was definitely caused by IMP. |
| Plasma Concentration Half-life (T1/2) | Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose) | Terminal elimination half-life (T1/2) = ln(2)/Kel |
| AUC From Administration to Infinity (AUC0-inf) | Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose) | AUC0-inf = AUC0-t + (Ct/Kel), where Ct was the last quantifiable concentration at time t. |
Countries
United Kingdom
Participant flow
Pre-assignment details
Total 60 subjects were screened and among them 16 subjects were screen failure, 2 subjects withdrew consent and 14 subjects were reserve.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Nurofen for Children® suspension 400 mg/20 mL single-oral dose under fasted and fed conditions.
Algifor Dolo Junior® suspension 400 mg/20 mL single-oral dose under fasted and fed conditions. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 2: Washout (3 to 7 Days) | Adverse Event | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 31.46 years STANDARD_DEVIATION 8.66 |
| Body Mass Index (BMI) | 24.07 kg/m² STANDARD_DEVIATION 1.884 |
| Height | 1.711 m STANDARD_DEVIATION 0.1 |
| Race/Ethnicity, Customized Caucasian | 28 Participants |
| Region of Enrollment United Kingdom | 28 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 15 Participants |
| Weight | 70.88 kg STANDARD_DEVIATION 10.909 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 28 |
| other Total, other adverse events | 11 / 28 |
| serious Total, serious adverse events | 0 / 28 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t)
Time frame: Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Population: Analysis population included only subjects with evaluable plasma concentrations per treatment and who had taken at least one dose of medication in each treatment groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Area Under the Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t) | 6139350.787 min*ng/mL | Standard Deviation 1315534.5598 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Area Under the Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t) | 5783712.850 min*ng/mL | Standard Deviation 1251017.0271 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Area Under the Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t) | 5912050.421 min*ng/mL | Standard Deviation 1353655.3076 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Area Under the Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t) | 5639716.354 min*ng/mL | Standard Deviation 1533625.9496 |
Primary
Maximum Plasma Concentration (Cmax)
Time frame: Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Population: Analysis population included only subjects with evaluable plasma concentrations per treatment and who had taken at least one dose of medication in each treatment groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Maximum Plasma Concentration (Cmax) | 37499.938 ng/mL | Standard Deviation 8983.302 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Maximum Plasma Concentration (Cmax) | 26207.273 ng/mL | Standard Deviation 5788.1116 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Maximum Plasma Concentration (Cmax) | 34752.646 ng/mL | Standard Deviation 5205.5859 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Maximum Plasma Concentration (Cmax) | 26377.382 ng/mL | Standard Deviation 7496.1966 |
Secondary
AUC From Administration to Infinity (AUC0-inf)
AUC0-inf = AUC0-t + (Ct/Kel), where Ct was the last quantifiable concentration at time t.
Time frame: Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Population: Analysis population included only subjects with evaluable plasma concentrations per treatment and who had taken at least one dose of medication in each treatment groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | AUC From Administration to Infinity (AUC0-inf) | 6215205.302 min*ng/mL | Standard Deviation 1324821.9469 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | AUC From Administration to Infinity (AUC0-inf) | 5927787.749 min*ng/mL | Standard Deviation 1283566.528 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | AUC From Administration to Infinity (AUC0-inf) | 5986690.115 min*ng/mL | Standard Deviation 1379614.0039 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | AUC From Administration to Infinity (AUC0-inf) | 5733877.552 min*ng/mL | Standard Deviation 1536788.1908 |
Secondary
Elimination Rate Constant (Kel)
Time frame: Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Population: Analysis population included only subjects with evaluable plasma concentrations per treatment and who had taken at least one dose of medication in each treatment groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Elimination Rate Constant (Kel) | 0.00599 1/min | Standard Deviation 0.001238 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Elimination Rate Constant (Kel) | 0.00533 1/min | Standard Deviation 0.001142 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Elimination Rate Constant (Kel) | 0.00602 1/min | Standard Deviation 0.001221 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Elimination Rate Constant (Kel) | 0.00557 1/min | Standard Deviation 0.001156 |
Secondary
Number of Subjects With Adverse Events (AEs).
Intensity was determined by the Investigator. For symptomatic AEs the following definitions were applied. Mild = AE did not limit usual activities; subject may have experienced slight discomfort. Moderate = AE resulted in some limitation of usual activities; subject may have experienced significant discomfort. Severe = AE resulted in an inability to carry out usual activities; subject may have experienced intolerable discomfort/pain. Relationship to Investigational Medicinal Products (IMP) Unassessable/Unclassified = Insufficient information to be able to make an assessment. Conditional/ Unclassified = Insufficient information to make an assessment at present. Unrelated = No possibility that AE was caused by IMP. Unlikely = Slight, but remote, chance that AE was caused by IMP. Possible = Reasonable suspicion that the AE was caused by IMP. Probable = Most likely that AE was caused by IMP. Certain = AE was definitely caused by IMP.
Time frame: Up to follow-up day 7
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Possible | 0 Participants |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Probable | 0 Participants |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Unassessable /Unclassifiable | 0 Participants |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Conditional/Unclassified | 0 Participants |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Intensity - Moderate | 0 Participants |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | TEAE Leading to Withdrawal | 0 Participants |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Treatment Emergent Adverse Event (TEAE) | 3 Participants |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Unrelated | 2 Participants |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Intensity - Severe | 0 Participants |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Unlikely | 1 Participants |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Serious TEAE | 0 Participants |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Intensity - Mild | 3 Participants |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Certain | 0 Participants |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Conditional/Unclassified | 0 Participants |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Serious TEAE | 0 Participants |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Unlikely | 2 Participants |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Probable | 0 Participants |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Possible | 1 Participants |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | TEAE Leading to Withdrawal | 1 Participants |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Treatment Emergent Adverse Event (TEAE) | 4 Participants |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Certain | 0 Participants |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Intensity - Mild | 2 Participants |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Unrelated | 1 Participants |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Intensity - Moderate | 2 Participants |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Unassessable /Unclassifiable | 0 Participants |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Intensity - Severe | 0 Participants |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Unlikely | 2 Participants |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Treatment Emergent Adverse Event (TEAE) | 7 Participants |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Serious TEAE | 0 Participants |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | TEAE Leading to Withdrawal | 1 Participants |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Intensity - Mild | 6 Participants |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Intensity - Moderate | 0 Participants |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Intensity - Severe | 1 Participants |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Certain | 0 Participants |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Probable | 0 Participants |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Possible | 0 Participants |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Unrelated | 5 Participants |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Conditional/Unclassified | 0 Participants |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Unassessable /Unclassifiable | 0 Participants |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Intensity - Severe | 0 Participants |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Unlikely | 1 Participants |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Intensity - Moderate | 1 Participants |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Treatment Emergent Adverse Event (TEAE) | 3 Participants |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Unrelated | 1 Participants |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Intensity - Mild | 2 Participants |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | TEAE Leading to Withdrawal | 0 Participants |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Unassessable /Unclassifiable | 0 Participants |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Conditional/Unclassified | 0 Participants |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Serious TEAE | 0 Participants |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Possible | 1 Participants |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Probable | 0 Participants |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Number of Subjects With Adverse Events (AEs). | Relationship to IMP - Certain | 0 Participants |
Secondary
Plasma Concentration at Each Planned Nominal Time-point (Cn)
Cn was derived using linear interpolation from the 2 samples taken either side of the nominal time where there was a sampling time deviation. For concentrations that were missing due to blood samples not being taken Cn was not derived.
Time frame: Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Population: Analysis population included only subjects with evaluable plasma concentrations per treatment and who had taken at least one dose of medication in each treatment groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 240 min | 9649.611 ng/mL | Standard Deviation 2767.9584 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 90 min | 26045.659 ng/mL | Standard Deviation 4445.1832 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 80 min | 27236.542 ng/mL | Standard Deviation 4944.7693 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 180 min | 14091.791 ng/mL | Standard Deviation 3856.4139 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 105 min | 23391.182 ng/mL | Standard Deviation 4298.8943 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 720 min | 560.199 ng/mL | Standard Deviation 343.236 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 120 min | 20702.122 ng/mL | Standard Deviation 4461.6587 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 20 min | 18776.528 ng/mL | Standard Deviation 13893.1674 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 30 min | 27860.671 ng/mL | Standard Deviation 12228.9507 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 10 min | 5934.077 ng/mL | Standard Deviation 6885.8643 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 480 min | 1942.286 ng/mL | Standard Deviation 948.4031 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 40 min | 31484.356 ng/mL | Standard Deviation 7963.3886 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 50 min | 32538.663 ng/mL | Standard Deviation 9976.7494 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 360 min | 3992.230 ng/mL | Standard Deviation 1611.5462 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 60 min | 30424.660 ng/mL | Standard Deviation 5407.6867 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 1440 min | 127.547 ng/mL | Standard Deviation 34.26 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 70 min | 28817.725 ng/mL | Standard Deviation 4189.7125 |
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 15 min | 12315.358 ng/mL | Standard Deviation 10819.4956 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 30 min | 16171.896 ng/mL | Standard Deviation 10459.1021 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 80 min | 21532.327 ng/mL | Standard Deviation 5367.9576 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 15 min | 8486.946 ng/mL | Standard Deviation 9318.9385 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 180 min | 13597.701 ng/mL | Standard Deviation 3653.1273 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 720 min | 829.589 ng/mL | Standard Deviation 460.9511 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 90 min | 20697.612 ng/mL | Standard Deviation 4961.1992 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 70 min | 22585.564 ng/mL | Standard Deviation 6387.266 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 240 min | 10997.109 ng/mL | Standard Deviation 3518.9434 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 40 min | 20109.864 ng/mL | Standard Deviation 9451.05 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 105 min | 19525.222 ng/mL | Standard Deviation 3347.9779 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 10 min | 5473.173 ng/mL | Standard Deviation 7955.4756 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 120 min | 18414.660 ng/mL | Standard Deviation 3038.3137 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 360 min | 5390.090 ng/mL | Standard Deviation 2071.2073 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 60 min | 22645.898 ng/mL | Standard Deviation 7482.6836 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 20 min | 11491.148 ng/mL | Standard Deviation 10579.532 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 1440 min | 149.707 ng/mL | Standard Deviation 36.4129 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 480 min | 2839.215 ng/mL | Standard Deviation 1352.4747 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 50 min | 22216.449 ng/mL | Standard Deviation 8667.4972 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 1440 min | 189.103 ng/mL | Standard Deviation 85.3662 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 720 min | 544.660 ng/mL | Standard Deviation 417.5077 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 10 min | 5579.436 ng/mL | Standard Deviation 5074.7709 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 15 min | 12251.837 ng/mL | Standard Deviation 9535.7628 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 20 min | 18346.910 ng/mL | Standard Deviation 12216.1356 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 30 min | 27557.463 ng/mL | Standard Deviation 10049.7928 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 40 min | 31258.579 ng/mL | Standard Deviation 7630.5525 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 50 min | 31026.608 ng/mL | Standard Deviation 6935.4647 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 60 min | 28751.529 ng/mL | Standard Deviation 6440.3355 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 70 min | 26979.890 ng/mL | Standard Deviation 6495.2967 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 80 min | 25528.950 ng/mL | Standard Deviation 6286.8439 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 90 min | 24080.631 ng/mL | Standard Deviation 6464.0707 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 105 min | 22336.377 ng/mL | Standard Deviation 5049.693 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 120 min | 20053.854 ng/mL | Standard Deviation 4561.3611 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 180 min | 13062.561 ng/mL | Standard Deviation 3345.8475 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 240 min | 9483.481 ng/mL | Standard Deviation 3427.9947 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 360 min | 3830.211 ng/mL | Standard Deviation 1667.1184 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 480 min | 1930.929 ng/mL | Standard Deviation 1069.7491 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 15 min | 8566.950 ng/mL | Standard Deviation 8227.2989 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 180 min | 12893.527 ng/mL | Standard Deviation 3436.8623 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 70 min | 21619.517 ng/mL | Standard Deviation 6805.8715 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 60 min | 22226.638 ng/mL | Standard Deviation 7893.6789 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 10 min | 4647.090 ng/mL | Standard Deviation 6289.5788 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 240 min | 9895.761 ng/mL | Standard Deviation 3586.4589 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 50 min | 23041.910 ng/mL | Standard Deviation 10063.5154 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 40 min | 21794.588 ng/mL | Standard Deviation 10810.9958 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 1440 min | 145.298 ng/mL | Standard Deviation 15.3467 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 360 min | 5612.610 ng/mL | Standard Deviation 4105.192 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 30 min | 17619.547 ng/mL | Standard Deviation 10451.6496 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 20 min | 11489.917 ng/mL | Standard Deviation 8402.4627 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 720 min | 788.223 ng/mL | Standard Deviation 646.7288 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 105 min | 18500.837 ng/mL | Standard Deviation 4736.1272 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 480 min | 2650.093 ng/mL | Standard Deviation 1697.3457 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 120 min | 17112.477 ng/mL | Standard Deviation 4579.0063 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 90 min | 20182.637 ng/mL | Standard Deviation 5379.6131 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration at Each Planned Nominal Time-point (Cn) | Time Post-Dose - 80 min | 21132.032 ng/mL | Standard Deviation 6103.8828 |
Secondary
Plasma Concentration Half-life (T1/2)
Terminal elimination half-life (T1/2) = ln(2)/Kel
Time frame: Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Population: Analysis population included only subjects with evaluable plasma concentrations per treatment and who had taken at least one dose of medication in each treatment groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Plasma Concentration Half-life (T1/2) | 121.122 min | Standard Deviation 28.6677 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Plasma Concentration Half-life (T1/2) | 137.555 min | Standard Deviation 37.6325 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Plasma Concentration Half-life (T1/2) | 120.879 min | Standard Deviation 30.5194 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Plasma Concentration Half-life (T1/2) | 130.460 min | Standard Deviation 30.7138 |
Secondary
Ratio of AUC0-t/AUC0-inf (AUCR)
Time frame: Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Population: Analysis population included only subjects with evaluable plasma concentrations per treatment and who had taken at least one dose of medication in each treatment groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Ratio of AUC0-t/AUC0-inf (AUCR) | 0.988 Ratio | Standard Deviation 0.0059 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Ratio of AUC0-t/AUC0-inf (AUCR) | 0.976 Ratio | Standard Deviation 0.0184 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Ratio of AUC0-t/AUC0-inf (AUCR) | 0.988 Ratio | Standard Deviation 0.0074 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Ratio of AUC0-t/AUC0-inf (AUCR) | 0.983 Ratio | Standard Deviation 0.0118 |
Secondary
Time to Cmax (Tmax)
Time frame: Pre-dose, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480, 720 and 1440 mins (Day 1, Post-dose)
Population: Analysis population included only subjects with evaluable plasma concentrations per treatment and who had taken at least one dose of medication in each treatment groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment B: Nurofen for Children® 400 mg/20 mL (Fasted) | Time to Cmax (Tmax) | 46.4 min | Standard Deviation 17.33 |
| Treatment A: Nurofen for Children® 400 mg/20 mL (Fed) | Time to Cmax (Tmax) | 72.0 min | Standard Deviation 33.7 |
| Treatment D: Algifor Dolo Junior® 400 mg/20 mL (Fasted) | Time to Cmax (Tmax) | 52.3 min | Standard Deviation 40.91 |
| Treatment C: Algifor Dolo Junior® 400 mg/20 mL (Fed) | Time to Cmax (Tmax) | 71.7 min | Standard Deviation 48.72 |