Bioequivalence of the Test Formulation
Conditions
Brief summary
Bioequivalence evaluation of Nurofen for Children® with reference formulation of Algifor® Junior by determining and comparing the rate and extent of absorption in both fed and fasted states
Interventions
Nurofen for Children® 400 mg/10 ml
DRUGAlgifor® Junior
Algifor® Junior 400 mg/20 ml
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
1. Subjects who had given written informed consent. 2. Age: ≥18 years ≤50 years. 3. Sex: Male or female subjects who were eligible for entry. 4. Female subject of childbearing potential with a negative pregnancy test at the screening visit and who were willing to use an effective method of contraception, if applicable (unless of non-childbearing potential or where abstaining from sexual intercourse was in line with the preferred and usual lifestyle of the subject) from first dose until 3 months after the final dose of Investigational Medicinal Product (IMP). Effective forms of contraception included: established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). 5. Female subject of non-child bearing potential with negative pregnancy test at the screening visit. For the purposes of this study, this was defined as the subject being amenorrheic for at least 12 consecutive months or at least 4 months post-surgical sterilisation (including bilateral fallopian tube ligation or bilateral oophorectomy with or without hysterectomy). Menopausal status was confirmed by demonstrating at screening that levels of follicle stimulating hormone (FSH) fell within the respective pathology reference range. In the event a subject's menopause status had been clearly established (for example, the subject indicated she had been amenorrheic for 10 years), but FSH levels were not consistent with a post-menopausal condition, determination of subject eligibility was at the discretion of the Principal Investigator following consultation with the Sponsor's Responsible Physician. 6. Male subject willing to use an effective method of contraception, if applicable (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 IMP. 7. Healthy subjects as determined by past medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory tests at screening. 8. Healthy subjects with a body mass index (BMI) of ≥20 and ≤27 kg/m2.
Exclusion criteria
1. Pregnant or lactating females. 2. A history and/or presence of significant disease of any body system, including psychiatric disorders as specified in Chapter 5 of the International Classification of Diseases (ICD) 10. 3. Any condition that may have interfered with the absorption, distribution, metabolism or excretion of drugs. 4. A history of allergy or intolerance (including angioedema, urticaria, bronchospasm and rhinitis) related to treatment with ibuprofen, aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), or the excipients of the formulations. 5. A history of or active peptic or duodenal ulcers or gastrointestinal bleed or upper gastro-intestinal bleed, or other significant gastro-intestinal disorders. 6. A history of frequent dyspepsia, e.g. heartburn or indigestion. 7. A history of migraine. 8. Users of nicotine products i.e. current smokers and ex-smokers who had smoked within the 6 months prior to dosing with the study medication or users of cigarette replacements (e.g. e-cigarettes, nicotine patches or gums). 9. A history of substance abuse (including alcohol). 10. High consumption of stimulating drinks (coffee, tea, cola, energy drinks etc. total caffeine intake per day above 300 mg (1 cup of coffee equated to 50 mg)). 11. Those with positive screen/test for drugs of abuse including alcohol on any occasion throughout the study. 12. 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.). 13. Ingestion of an over-the-counter preparation within 7 days before dosing with study medication, including herbal medications, vitamin/fish oil supplements, ibuprofen and other NSAID. 14. Donation of blood in quantity \>400 mL, e.g., to the blood transfusion service in the previous 12 weeks before enrolment into the study. 15. Known human immune deficiency virus (HIV) positive status, or a positive viral serology screen. 16. Topical use of ibuprofen within 7 days before dosing with IMP. 17. Those previously randomized into this study. 18. Employee at study site. 19. Partner or first degree relative of the Investigator. 20. Those who have participated in a clinical trial in the previous 12 weeks. 21. Those unable, in the opinion of the Investigator, to comply fully with the study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of Ibuprofen | Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose | One Subject in Period 3 Reference (fasted) was not included in PK Parameter Summary Set as per statistical analysis plan (SAP) Population definitions. |
| Area Under Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t) of Ibuprofen | Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of AUC0-t/AUC0-inf (AUCR) | Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose | — |
| Time to Maximum Plasma Concentration (Tmax) of Ibuprofen | Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose | — |
| Elimination Rate Constant (Kel) of Ibuprofen | Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose | 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 maximized the adjusted R2. |
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Up to Day 7 (follow-up) | Mild = Adverse event (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. 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 the AE was caused by the IMP Unlikely = Slight, but remote, chance that the AE was caused by the IMP, but the balance of judgment was that it was most likely not due to the investigational medicinal product (IMP). Possible = Reasonable suspicion that the AE was caused by the IMP Probable = Most likely that the AE was caused by the IMP Certain = AE was definitely caused by the IMP |
| Plasma Concentration Half-life (T1/2) of Ibuprofen | Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose | — |
| Area Under Plasma Concentration-time Curve From Administration to Infinity (AUC0-inf) of Ibuprofen | Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose | AUC0-inf was calculated as AUC0-t + (Ct/Kel) where Ct was the last quantifiable concentration at time t. |
Participant flow
Recruitment details
Study was conducted in single-site in the United Kingdom.
Pre-assignment details
Total 71 subjects were screened. Of these, 38 subjects were screen failures, 2 were withdrew consent, 7 were reserve subjects. Subjects randomized were 24.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Nurofen for Children® 400 mg/10 mL single-oral dose under fasted and fed conditions.
Algifor® Junior 400 mg/20 mL single-oral dose under fasted and fed conditions. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 29.5 years STANDARD_DEVIATION 8.21 |
| Body Mass Index | 23.82 kg/m² STANDARD_DEVIATION 2.037 |
| Height | 1.692 meter STANDARD_DEVIATION 0.0935 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 11 Participants |
| Weight | 68.68 kg STANDARD_DEVIATION 11.506 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 2 / 24 | 1 / 24 | 1 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Area Under Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t) of Ibuprofen
Time frame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
Population: PK Parameter Summary set population. One Subject in Period 3 Reference (fasted) was not included in PK Parameter Summary Set as per statistical analysis plan (SAP) Population definitions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Fasted): Nurofen for Children | Area Under Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t) of Ibuprofen | 6169.662 min*μg/mL | Standard Deviation 1199.1785 |
| Test (Fed): Nurofen for Children | Area Under Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t) of Ibuprofen | 5754.831 min*μg/mL | Standard Deviation 1056.5014 |
| Reference (Fasted): Algifor Junior | Area Under Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t) of Ibuprofen | 5960.054 min*μg/mL | Standard Deviation 832.1342 |
| Reference (Fed): Algifor Junior | Area Under Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t) of Ibuprofen | 5482.340 min*μg/mL | Standard Deviation 827.2913 |
90% CI: [96.28, 107.16]
90% CI: [101.4, 107.63]
Primary
Maximum Plasma Concentration (Cmax) of Ibuprofen
One Subject in Period 3 Reference (fasted) was not included in PK Parameter Summary Set as per statistical analysis plan (SAP) Population definitions.
Time frame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
Population: Pharmacokinetics (PK) Parameter Summary Set population: All subjects from the PK dataset with evaluable PK parameters for each treatment period. (PK Dataset: All subjects from the safety population with evaluable plasma concentrations).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Fasted): Nurofen for Children | Maximum Plasma Concentration (Cmax) of Ibuprofen | 38.503 μg/ml | Standard Deviation 7.5696 |
| Test (Fed): Nurofen for Children | Maximum Plasma Concentration (Cmax) of Ibuprofen | 25.162 μg/ml | Standard Deviation 6.9668 |
| Reference (Fasted): Algifor Junior | Maximum Plasma Concentration (Cmax) of Ibuprofen | 33.843 μg/ml | Standard Deviation 3.7858 |
| Reference (Fed): Algifor Junior | Maximum Plasma Concentration (Cmax) of Ibuprofen | 26.432 μg/ml | Standard Deviation 6.129 |
90% CI: [85.81, 103.38]
90% CI: [103.84, 120.07]
Secondary
Area Under Plasma Concentration-time Curve From Administration to Infinity (AUC0-inf) of Ibuprofen
AUC0-inf was calculated as AUC0-t + (Ct/Kel) where Ct was the last quantifiable concentration at time t.
Time frame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
Population: PK Parameter Summary set population. One Subject in Period 3 Reference (fasted) was not included in PK Parameter Summary Set as per statistical analysis plan (SAP) Population definitions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Fasted): Nurofen for Children | Area Under Plasma Concentration-time Curve From Administration to Infinity (AUC0-inf) of Ibuprofen | 6255.821 min*μg/mL | Standard Deviation 1229.6414 |
| Test (Fed): Nurofen for Children | Area Under Plasma Concentration-time Curve From Administration to Infinity (AUC0-inf) of Ibuprofen | 5982.084 min*μg/mL | Standard Deviation 1118.9361 |
| Reference (Fasted): Algifor Junior | Area Under Plasma Concentration-time Curve From Administration to Infinity (AUC0-inf) of Ibuprofen | 6032.841 min*μg/mL | Standard Deviation 843.8379 |
| Reference (Fed): Algifor Junior | Area Under Plasma Concentration-time Curve From Administration to Infinity (AUC0-inf) of Ibuprofen | 5609.733 min*μg/mL | Standard Deviation 862.2304 |
Secondary
Elimination Rate Constant (Kel) of Ibuprofen
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 maximized the adjusted R2.
Time frame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
Population: PK Parameter Summary set population. One Subject in Period 3 Reference (fasted) was not included in PK Parameter Summary Set as per statistical analysis plan (SAP) Population definitions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Fasted): Nurofen for Children | Elimination Rate Constant (Kel) of Ibuprofen | 0.00646 1/min | Standard Deviation 0.000763 |
| Test (Fed): Nurofen for Children | Elimination Rate Constant (Kel) of Ibuprofen | 0.00532 1/min | Standard Deviation 0.00119 |
| Reference (Fasted): Algifor Junior | Elimination Rate Constant (Kel) of Ibuprofen | 0.00668 1/min | Standard Deviation 0.000763 |
| Reference (Fed): Algifor Junior | Elimination Rate Constant (Kel) of Ibuprofen | 0.00577 1/min | Standard Deviation 0.000865 |
Secondary
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
Mild = Adverse event (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. 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 the AE was caused by the IMP Unlikely = Slight, but remote, chance that the AE was caused by the IMP, but the balance of judgment was that it was most likely not due to the investigational medicinal product (IMP). Possible = Reasonable suspicion that the AE was caused by the IMP Probable = Most likely that the AE was caused by the IMP Certain = AE was definitely caused by the IMP
Time frame: Up to Day 7 (follow-up)
Population: Safety population: All subjects who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Test (Fasted): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Certain | 0 Participants |
| Test (Fasted): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Unassessable/Unclassifiable | 0 Participants |
| Test (Fasted): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Probable | 0 Participants |
| Test (Fasted): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Possible | 0 Participants |
| Test (Fasted): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Unrelated | 3 Participants |
| Test (Fasted): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE Leading to Withdrawal | 0 Participants |
| Test (Fasted): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Unlikely | 0 Participants |
| Test (Fasted): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE by severity: Mild | 3 Participants |
| Test (Fasted): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Conditional/Unclassified | 0 Participants |
| Test (Fasted): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Treatment Emergent Adverse Event (TEAE) | 3 Participants |
| Test (Fasted): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE by severity: Moderate | 0 Participants |
| Test (Fasted): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Serious TEAE | 0 Participants |
| Test (Fasted): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE by severity: Severe | 0 Participants |
| Test (Fed): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Serious TEAE | 0 Participants |
| Test (Fed): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE Leading to Withdrawal | 0 Participants |
| Test (Fed): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE by severity: Mild | 1 Participants |
| Test (Fed): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Certain | 0 Participants |
| Test (Fed): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Probable | 0 Participants |
| Test (Fed): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Unassessable/Unclassifiable | 0 Participants |
| Test (Fed): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Treatment Emergent Adverse Event (TEAE) | 1 Participants |
| Test (Fed): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE by severity: Severe | 0 Participants |
| Test (Fed): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Possible | 0 Participants |
| Test (Fed): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Unrelated | 1 Participants |
| Test (Fed): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE by severity: Moderate | 0 Participants |
| Test (Fed): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Conditional/Unclassified | 0 Participants |
| Test (Fed): Nurofen for Children | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Unlikely | 0 Participants |
| Reference (Fasted): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE by severity: Moderate | 0 Participants |
| Reference (Fasted): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Unrelated | 1 Participants |
| Reference (Fasted): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE Leading to Withdrawal | 0 Participants |
| Reference (Fasted): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Conditional/Unclassified | 0 Participants |
| Reference (Fasted): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Treatment Emergent Adverse Event (TEAE) | 1 Participants |
| Reference (Fasted): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Unassessable/Unclassifiable | 0 Participants |
| Reference (Fasted): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE by severity: Mild | 1 Participants |
| Reference (Fasted): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Unlikely | 0 Participants |
| Reference (Fasted): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE by severity: Severe | 0 Participants |
| Reference (Fasted): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Certain | 0 Participants |
| Reference (Fasted): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Serious TEAE | 0 Participants |
| Reference (Fasted): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Probable | 0 Participants |
| Reference (Fasted): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Possible | 0 Participants |
| Reference (Fed): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Probable | 0 Participants |
| Reference (Fed): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Treatment Emergent Adverse Event (TEAE) | 0 Participants |
| Reference (Fed): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Serious TEAE | 0 Participants |
| Reference (Fed): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE Leading to Withdrawal | 0 Participants |
| Reference (Fed): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE by severity: Mild | 0 Participants |
| Reference (Fed): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE by severity: Moderate | 0 Participants |
| Reference (Fed): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE by severity: Severe | 0 Participants |
| Reference (Fed): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Certain | 0 Participants |
| Reference (Fed): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Unassessable/Unclassifiable | 0 Participants |
| Reference (Fed): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Possible | 0 Participants |
| Reference (Fed): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Unlikely | 0 Participants |
| Reference (Fed): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Unrelated | 0 Participants |
| Reference (Fed): Algifor Junior | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Relationship to IMP - Conditional/Unclassified | 0 Participants |
Secondary
Plasma Concentration Half-life (T1/2) of Ibuprofen
Time frame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
Population: PK Parameter Summary set population. One Subject in Period 3 Reference (fasted) was not included in PK Parameter Summary Set as per statistical analysis plan (SAP) Population definitions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Fasted): Nurofen for Children | Plasma Concentration Half-life (T1/2) of Ibuprofen | 108.854 min | Standard Deviation 13.1303 |
| Test (Fed): Nurofen for Children | Plasma Concentration Half-life (T1/2) of Ibuprofen | 138.894 min | Standard Deviation 41.0392 |
| Reference (Fasted): Algifor Junior | Plasma Concentration Half-life (T1/2) of Ibuprofen | 104.975 min | Standard Deviation 11.6362 |
| Reference (Fed): Algifor Junior | Plasma Concentration Half-life (T1/2) of Ibuprofen | 122.752 min | Standard Deviation 19.338 |
Secondary
Ratio of AUC0-t/AUC0-inf (AUCR)
Time frame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
Population: PK Parameter Summary set population. One Subject in Period 3 Reference (fasted) was not included in PK Parameter Summary Set as per statistical analysis plan (SAP) Population definitions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Fasted): Nurofen for Children | Ratio of AUC0-t/AUC0-inf (AUCR) | 0.987 Ratio | Standard Deviation 0.0066 |
| Test (Fed): Nurofen for Children | Ratio of AUC0-t/AUC0-inf (AUCR) | 0.963 Ratio | Standard Deviation 0.0384 |
| Reference (Fasted): Algifor Junior | Ratio of AUC0-t/AUC0-inf (AUCR) | 0.988 Ratio | Standard Deviation 0.0052 |
| Reference (Fed): Algifor Junior | Ratio of AUC0-t/AUC0-inf (AUCR) | 0.978 Ratio | Standard Deviation 0.0142 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of Ibuprofen
Time frame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
Population: PK Parameter Summary set population. One Subject in Period 3 Reference (fasted) was not included in PK Parameter Summary Set as per statistical analysis plan (SAP) Population definitions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Fasted): Nurofen for Children | Time to Maximum Plasma Concentration (Tmax) of Ibuprofen | 60.4 min | Standard Deviation 43.59 |
| Test (Fed): Nurofen for Children | Time to Maximum Plasma Concentration (Tmax) of Ibuprofen | 65.8 min | Standard Deviation 24.79 |
| Reference (Fasted): Algifor Junior | Time to Maximum Plasma Concentration (Tmax) of Ibuprofen | 65 min | Standard Deviation 33.81 |
| Reference (Fed): Algifor Junior | Time to Maximum Plasma Concentration (Tmax) of Ibuprofen | 74.9 min | Standard Deviation 42.66 |