Bioequivalence Study of Ibuprofen 200 mg/5 mL Oral Suspension vs. MOMENT 200 mg Coated Tablet

• Register: ClinicalTrials.gov
• Last refreshed on: 26 September 2016
• Main ID: NCT02902289
• Date of registration: 07/09/2016
• Prospective Registration: No
• Primary sponsor: Aziende Chimiche Riunite Angelini Francesco S.p.A
• Public title: Bioequivalence Study of Ibuprofen 200 mg/5 mL Oral Suspension vs. MOMENT 200 mg Coated Tablet
• Scientific title: Bioequivalence Study of a New Formulation of Ibuprofen 200 mg/5 mL Oral Suspension vs. the Reference Product MOMENT 200 mg Coated Tablet in Healthy Volunteers
• Date of first enrolment: June 2016
• Target sample size: 60
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02902289
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label
• Phase: Phase 1

Countries of recruitment

Switzerland

Contacts

• Name: Milko Radicioni, MD
• Affiliation: Cross Research S.A.

Key inclusion & exclusion criteria

Inclusion Criteria:

To be enrolled in this study, subjects must fulfil all these criteria:

1. Informed consent: signed written informed consent before inclusion in the study

2. Sex and Age: males/females, 18-55 years old inclusive

3. Body mass index (BMI): 18.5-30 kg/m2 inclusive

4. Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure
(DBP) 50-89 mmHg, heart rate (HR) 50-90 bpm, measured after 5 min at rest in the
sitting position

5. Full comprehension: ability to comprehend the full nature and purpose of the study,
including possible risks and side effects; ability to co-operate with the
investigator and to comply with the requirements of the entire study

6. Contraception and fertility (females only): females of child-bearing potential must
be using at least one of the following reliable methods of contraception:

1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at
least 2 months before the screening visit

2. A non-hormonal intrauterine device [IUD] or female condom with spermicide or
contraceptive sponge with spermicide or diaphragm with spermicide or cervical
cap with spermicide for at least 2 months before the screening visit

3. A male sexual partner who agrees to use a male condom with spermicide

4. A sterile sexual partner Female participants of non-child-bearing potential or
in post-menopausal status for at least 1 year will be admitted. For all female
subjects, pregnancy test result must be negative at screening and day -1.

Exclusion Criteria:

1. Electrocardiogram (12-leads, supine position): clinically significant abnormalities

2. Physical findings: clinically significant abnormal physical findings which could
interfere with the objectives of the study

3. Laboratory analyses: clinically significant abnormal laboratory values indicative of
physical illness

4. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or
formulations' ingredients or related drugs, namely non-steroidal anti-inflammatory
agents (NSAIDs); history of anaphylaxis to drugs or allergic reactions in general,
which the investigator considers may affect the outcome of the study

5. Diseases: history of significant renal, hepatic, gastrointestinal (in particular
gastroduodenal ulcer and bleeding), cardiovascular, respiratory (in particular
asthma), skin, haematological, endocrine or neurological diseases that may interfere
with the aim of the study

6. Medications: medications, including over the counter (OTC) (in particular ibuprofen)
medications and herbal products for 2 weeks before the start of the study. Hormonal
contraceptives for females will be allowed

7. Investigative drug studies: participation in the evaluation of any investigational
product for 3 months before this study. The 3-month interval is calculated as the
time between the first calendar day of the month that follows the last visit of the
previous study and the first day of the present study

8. Blood donation: blood donations for 3 months before this study

9. Drug, alcohol, caffeine, tobacco: history of drug, alcohol [>1 drink/day for females
and >2 drinks/day for males, defined according to USDA Dietary Guidelines 2015-2020
(10)], caffeine (>5 cups coffee/tea/day) or tobacco abuse (=10 cigarettes/day)

10. Drug test: positive result at the drug test at screening or day-1

11. Alcohol test: positive alcohol breath test at day -1

12. Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating
habits in the 4 weeks before this study; vegetarians

13. Pregnancy (females only): positive or missing pregnancy test at screening or day
-1,pregnant or lactating women



Age minimum: 18 Years
Age maximum: 55 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Healthy

Intervention(s)

Drug: Ibuprofen 200 mg/5 mL oral suspension

Drug: MOMENT 200 mg coated tablet

Primary Outcome(s)

AUC(0-t) of (S)-ibuprofen after single dose administration under fasting conditions of test and reference formulations containing racemic ibuprofen. [Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose]

Cmax of (S)-ibuprofen after single dose administration under fasting conditions of test and reference formulations containing racemic ibuprofen. [Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose]

Secondary Outcome(s)

Apparent First order terminal rate constant (?z) of ibuprofen racemate and of (S)-ibuprofen and (R)-ibuprofen after single dose administration under fasting conditions of test and reference formulations [Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose]

A descriptive evaluation of palatability for the test formulation will be performed. Smell, taste and texture parameters will be evaluated immediately after drug administration through a 5-point rating scale. [Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose]

Treatment-Emergent Adverse Event (TEAEs), vital signs (BP, HR), physical examination, body weight and laboratory parameters [Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose]

Extrapolated area calculated as (AUC(0-8) - AUC(0-t))/AUC(0-8) (residual area) of ibuprofen racemate and of (S)-ibuprofen and (R)-ibuprofen after single dose administration under fasting conditions of test and reference formulations [Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose]

Peak drug concentration (Cmax) of racemic ibuprofen and (R)-ibuprofen after single dose administration under fasting conditions of test and reference formulations [Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose]

Time Until First Nonzero Concentration (tlag) of ibuprofen racemate and of (S)-ibuprofen and (R)-ibuprofen after single dose administration under fasting conditions of test and reference formulations [Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose]

Area under the concentration-time curve from time zero to time t (AUC(0-t)) ratio of the two enantiomers (S/R) after single dose administration under fasting conditions of test and reference formulations [Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose]

Half-life lambda z (/t1/2,z) of ibuprofen racemate and of (S)-ibuprofen and (R)-ibuprofen after single dose administration under fasting conditions of test and reference formulations [Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose]

Time to achieve Cmax (Tmax) of ibuprofen racemate and of (S)-ibuprofen and (R)-ibuprofen after single dose administration under fasting conditions of test and reference formulations [Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose]

Area under the concentration vs. time curve up to infinity (AUC(0-8)) of ibuprofen racemate and of (S)-ibuprofen and (R)-ibuprofen after single dose administration under fasting conditions of test and reference formulations [Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose]

Area under the concentration-time curve from time zero to time t (AUC(0-t)) of racemic ibuprofen and (R)-ibuprofen after single dose administration under fasting conditions of test and reference formulations [Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose]

Secondary ID(s)

CRO-PK-15-306

070(Q)HO15411

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Cross Research S.A.