Ibuprofen 4% (w/v) Pivotal Bioequivalence Study | NCT03496324

NCT03496324

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2015-003894-13	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Test (fed): Nurofen for Children	Active Comparator	Nurofen for Children® 400 mg/10 ml by mouth under fed condition Subjects participated in Treatment Sequence: BACD, DCAB, ADBC and CBDA.	Drug: Nurofen for Children®
Test (fasted): Nurofen for Children	Active Comparator	Nurofen for Children® 400 mg/10 ml by mouth under fasted condition. Subjects participated in Treatment Sequence: BACD, DCAB, ADBC and CBDA.	Drug: Nurofen for Children®
Reference (fed): Algifor Junior	Experimental	Algifor® Junior 400 mg/20 ml by mouth under fed condition. Subjects participated in Treatment Sequence: BACD, DCAB, ADBC and CBDA.	Drug: Algifor® Junior
Reference (fasted): Algifor Junior	Experimental	Algifor® Junior 400 mg/20 ml by mouth under fasted condition. Subjects participated in Treatment Sequence: BACD, DCAB, ADBC and CBDA.	Drug: Algifor® Junior

Name	Type	Description	Arm Group Labels	Other Names
Nurofen for Children®	Drug	Nurofen for Children® 400 mg/10 ml	Test (fasted): Nurofen for Children Test (fed): Nurofen for Children

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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 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 Outcomes

Measure	Description	Time Frame
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.	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

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects who had given written informed consent.
Age: ≥18 years ≤50 years.
Sex: Male or female subjects who were eligible for entry.
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).
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.
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.
Healthy subjects as determined by past medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory tests at screening.
Healthy subjects with a body mass index (BMI) of ≥20 and ≤27 kg/m2.

Exclusion Criteria:

Pregnant or lactating females.
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.
Any condition that may have interfered with the absorption, distribution, metabolism or excretion of drugs.
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.
A history of or active peptic or duodenal ulcers or gastrointestinal 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.
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).
A history of substance abuse (including alcohol).
High consumption of stimulating drinks (coffee, tea, cola, energy drinks etc. total caffeine intake per day above 300 mg (1 cup of coffee equated to 50 mg)).
Those with positive screen/test for drugs of abuse 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, including herbal medications, vitamin/fish oil supplements, ibuprofen and other NSAID.
Donation of blood in quantity >400 mL, e.g., to the blood transfusion service 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 IMP.
Those previously randomized 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.

Arm/Group Information

ID	Title	Description
FG000	Sequence 1-BACD: Test (Fed) - Nurofen for Children	B = Nurofen for Children® 400 mg/10 ml (Test fasted) A = Nurofen for Children® 400 mg/10 ml (Test fed) C = Algifor® Junior 400 mg/20 ml (Reference fed) D = Algifor® Junior 400 mg/20 ml (Reference fasted)
FG001	Sequence 2-DCAB: Test (Fasted) - Nurofen for Children	D = Algifor® Junior 400 mg/20 ml (Reference fasted) C = Algifor® Junior 400 mg/20 ml (Reference fed) A = Nurofen for Children® 400 mg/10 ml (Test fed) B = Nurofen for Children® 400 mg/10 ml (Test fasted)
FG002	Sequence 3-ADBC: Reference (Fed) - Algifor Junior	A = Nurofen for Children® 400 mg/10 ml (Test fed) D = Algifor® Junior 400 mg/20 ml (Reference fasted) B = Nurofen for Children® 400 mg/10 ml (Test fasted) C = Algifor® Junior 400 mg/20 ml (Reference fed)
FG003	Sequence 4-CBDA: Reference (Fasted) - Algifor Junior	C = Algifor® Junior 400 mg/20 ml (Reference fed) B = Nurofen for Children® 400 mg/10 ml (Test fasted) D = Algifor® Junior 400 mg/20 ml (Reference fasted) A = Nurofen for Children® 400 mg/10 ml (Test fed)

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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).

Posted

Mean

Standard Deviation

μg/ml

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

ID	Title	Description
OG000	Test (Fasted): Nurofen for Children	Nurofen for Children® 400 mg/10 ml by mouth under fasted condition. Subjects participated in Treatment Sequence: BACD, DCAB, ADBC and CBDA. Nurofen for Children®: Nurofen for Children® 400 mg/10 ml

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Test (Fasted): Nurofen for Children	Nurofen for Children® 400 mg/10 ml by mouth under fasted condition. Subjects participated in Treatment Sequence: BACD, DCAB, ADBC and CBDA. Nurofen for Children®: Nurofen for Children® 400 mg/10 ml