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

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

The main objective of the study is to evaluate the bioequivalence of a new formulation of ibuprofen 200 mg/5 mL oral suspension vs. the marketed reference product MOMENT 200 mg coated tablet, when administered under fasting conditions as single oral dose to healthy male and female volunteers, in two consecutive study periods.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ibuprofen 200 mg/5 mL oral suspension; Drug: MOMENT 200 mg coated tablet

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Arzo, Switzerland, CH-6864
    • CROSS Research S.A., Phase I Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ibuprofen 200 mg/5 mL oral suspension; Single dose of 1 ibuprofen 200 mg/5 mL stick administered under fasting conditions in two consecutive periods, with a wash-out interval of at least 7 days between consecutive administrations.	Drug: Ibuprofen 200 mg/5 mL oral suspension
ACTIVE_COMPARATOR: MOMENT 200 mg coated tablet; Single dose of 1 MOMENT 200 mg coated tablet administered under fasting conditions in two consecutive periods, with a wash-out interval of at least 7 days between consecutive administrations.	Drug: MOMENT 200 mg coated tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of (S)-ibuprofen after single dose administration under fasting conditions of test and reference formulations containing racemic ibuprofen.	Maximum plasma concentration (μg/ml)	0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose
AUC(0-t) of (S)-ibuprofen after single dose administration under fasting conditions of test and reference formulations containing racemic ibuprofen.	Area under the plasma concentration-time curve from administration time to the time (t) of the last measurable concentration (Ct ), calculated with the linear trapezoidal method (μg*h/ml)	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 Measures

Outcome Measure	Measure Description	Time Frame
Peak drug concentration (Cmax) of racemic ibuprofen and (R)-ibuprofen after single dose administration under fasting conditions of test and reference formulations		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		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	Area under the concentration-time curve extrapolated to infinity, calculated, if feasible, as AUC(0-t) + Ct/λz, where Ct is the last measurable drug concentration (μg*h/ml)	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-∞)) of ibuprofen racemate and of (S)-ibuprofen and (R)-ibuprofen after single dose administration under fasting conditions of test and reference formulations		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-∞) - AUC(0-t))/AUC(0-∞) (residual area) of ibuprofen racemate and of (S)-ibuprofen and (R)-ibuprofen after single dose administration under fasting conditions of test and reference formulations		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		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		0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose
Apparent First order terminal rate constant (λz) of ibuprofen racemate and of (S)-ibuprofen and (R)-ibuprofen after single dose administration under fasting conditions of test and reference formulations		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		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		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.		0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 hours post-dose

Collaborators and Investigators

• Sponsor: Aziende Chimiche Riunite Angelini Francesco S.p.A
• Collaborators: Cross Research S.A.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (ACTUAL): July 1, 2016
• Study Completion (ACTUAL): July 1, 2016

Study Registration Dates

• First Submitted: September 7, 2016
• First Submitted That Met QC Criteria: September 12, 2016
• First Posted (ESTIMATE): September 15, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): September 15, 2016
• Last Update Submitted That Met QC Criteria: September 12, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Bioequivalence; Oral Suspension; Ibuprofen 200 mg/5 ml; Moment 200 mg coated tablet
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: 070(Q)HO15411; CRO-PK-15-306 (OTHER: CROSS Research S.A., Phase I Unit)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO