Bioequivalence of the Test FormulationPhase 1NCT03496324
Ibuprofen 4% (w/v) Pivotal Bioequivalence Study
A Phase 1 study testing Nurofen for Children® and Algifor® Junior in people with Bioequivalence of the Test Formulation, run by Reckitt Benckiser Healthcare (UK) Limited.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Bioequivalence of the Test Formulation
- What is being tested?
- Nurofen for Children® and Algifor® Junior
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- No sites listed yet
- Study dates
- 29 Feb 2016to 6 May 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
About this study
Official title: A Randomised, Single-dose, 4-way Crossover, Open-label, Pharmacokinetic Study Comparing a 4% (w/v) Suspension of Ibuprofen With a Reference 2% (w/v) Suspension of Ibuprofen in the Fed and Fasted States.
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
- Conditions
- Bioequivalence of the Test Formulation
- Being tested
- Nurofen for Children®, Algifor® Junior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nurofen for Children®Drug
Also called NfC®
Nurofen for Children® 400 mg/10 ml
Algifor® JuniorDrug
Also called Ibuprofen oral suspension
Algifor® Junior 400 mg/20 ml
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Algifor® Junior |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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 (6)
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.
Measured: 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
AUC0-inf was calculated as AUC0-t + (Ct/Kel) where Ct was the last quantifiable concentration at time t.
Measured: 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
Ratio of AUC0-t/AUC0-inf (AUCR)
Measured: 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
Measured: 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
Plasma Concentration Half-life (T1/2) of Ibuprofen
Measured: 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
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
Measured: Up to Day 7 (follow-up)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2018
- Study start29 Feb 2016
- Primary completion6 May 2016
- Study completion6 May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Bioequivalence of the Test FormulationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Reckitt Benckiser Healthcare (UK) Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03496324
- Sponsor's protocol ID
- RB7-UK-1509
- Other IDs
- 2015-003894-13, 2015
- Status last verified
- Feb 2019
- First submitted
- 5 Apr 2018
- Last updated
- 5 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Single-dose, 4-way Crossover, Open-label, Pharmacokinetic Study Comparing a 4% (w/v) Suspension of Ibuprofen With a Reference 2% (w/v) Suspension of Ibuprofen in the Fed and Fasted States.
- ClinicalTrials.gov ID
- NCT03496324
- Acronym / sponsor ID
- RB7-UK-1509
- Conditions
- Bioequivalence of the Test Formulation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Reckitt Benckiser Healthcare (UK) LimitedIndustry (pharma, biotech, devices)
- Study start
- 29 Feb 2016 (actual)
- Primary completion
- 6 May 2016 (actual)
- Study completion
- 6 May 2016 (actual)
- First posted
- 12 Apr 2018 (actual)
- Results
- Posted 5 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Test (fed): Nurofen for Children | Active comparator | Drug: Nurofen for Children®Nurofen for Children® 400 mg/10 ml by mouth under fed condition Subjects participated in Treatment Sequence: BACD, DCAB, ADBC and CBDA. |
| Test (fasted): Nurofen for Children | Active comparator | Drug: 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. |
| Reference (fed): Algifor Junior | Experimental | Drug: Algifor® JuniorAlgifor® Junior 400 mg/20 ml by mouth under fed condition. Subjects participated in Treatment Sequence: BACD, DCAB, ADBC and CBDA. |
| Reference (fasted): Algifor Junior | Experimental | Drug: Algifor® JuniorAlgifor® Junior 400 mg/20 ml by mouth under fasted condition. Subjects participated in Treatment Sequence: BACD, DCAB, ADBC and CBDA. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nurofen for Children®Also: NfC®Nurofen for Children® 400 mg/10 ml | Drug | Test (fasted): Nurofen for Children, Test (fed): Nurofen for Children |
| Algifor® JuniorAlso: Ibuprofen oral suspensionAlgifor® Junior 400 mg/20 ml | Drug | Reference (fasted): Algifor Junior, Reference (fed): Algifor Junior |
Primary outcome
Maximum Plasma Concentration (Cmax) 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
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
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
6 secondary outcomes
Elimination Rate Constant (Kel) 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
Area Under Plasma Concentration-time Curve From Administration to Infinity (AUC0-inf) 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
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
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
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
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to Day 7 (follow-up)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nurofen for Children® and Algifor® Junior in people with Bioequivalence of the Test Formulation, run by Reckitt Benckiser Healthcare (UK) Limited.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Plasma Concentration (Cmax) 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2019.