To Evaluate the Food Effect and the Absorption Profile of Ibuprofen Controlled-Release Tablets 600 mg in Comparison to the Reference Standard Ibuprofen Tablets in Normal Healthy Volunteers

A Randomized, 4-way Crossover Study to Evaluate the Food Effect and the Absorption Profile of Investigational Product of "Ibuprofen Controlled-Release Tablets 600 mg" in Comparison to the Reference Standard Ibuprofen Tablets 200 mg in Normal Healthy Volunteers

To evaluate the food effect of Ibuprofen CR Tablets 600 mg (IBUCR), and its bioavailability comparison versus 3 doses of the reference arms including Advil® Ibuprofen Tablets 200 mg (IBUAdv) and Motrin® IB Ibuprofen Tablets 200 mg (IBUMot) in normal healthy volunteers.

Study Overview

• Status: Terminated
• Conditions: Pain Control
• Intervention / Treatment: Drug: Ibuprofen CR Tablets 600 mg; Drug: Advil Ibuprofen table 200 mg; Drug: Motrin IB Ibuprofen Tablets 200 mg

Detailed Description

This randomized, open label, four-way crossover phase I study is to evaluate the food effect of Ibuprofen CR Tablets 600 mg (IBUCR), and its bioavailability comparison versus 3 doses of the reference arms including Advil® Ibuprofen Tablets 200 mg (IBUAdv) and Motrin® IB Ibuprofen Tablets 200 mg (IBUMot) in normal healthy volunteers.

This study will enroll at least 26 evaluable subjects. The duration for test and reference treatments is 24 to 32 hours with a washout period of at least 5 days after the last dose administration of study drugs. The total study will take at least 28 days.

Subjects who meet all eligible requirements for participating in the study will receive all following interventions according to one of the 4 random sequences by Williams design.

1. One tablet of IBUCR 600 mg under fasting condition
2. One tablet of IBUCR 600 mg under fed condition
3. IBUAdv with a 4-hour dosing interval for 3 tablets (3×200 mg, q4h) under fasting condition
4. IBUMot with a 4-hour doing interval for 3 tablets (3×200 mg, q4h) under fasting condition

The blood sampling schedule are described as follows:

-For subjects receiving IBUCR (fed and fasted): Before dose administration (blank) and at 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 12h, 18h, 24h, 28h, 32h post-dose (A total of 17 samples per subject)

-For subjects receiving IBUAdv/IBUMot (fasted): Before dose administration (blank) and at 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 8h, 8.5h, 9h, 9.5h, 10h, 10.5h, 11h, 12h, 16h, 20h, 24h post-dose (A total of 25 samples per subject)

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Tri-Service General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects are 20 years of age or older.

2. Subjects whose body mass index (BMI) at screening is within a range of ≧18.5 kg/m2 and <25.0 kg/m2.

   BMI = Body Weight (kg) / [Height (m)]2 And body weight is not less than 50 kg and 45 kg for males and females, respectively.

3. Subject's medical history shows no contraindication to the test medications (hypersensitivity to ibuprofen or any component of test and reference products).
4. Subjects who are judged to be in good health by the investigator based upon the results of physical examinations (PEs), chest X-ray (within 180 days prior to the first dose of the study) and routine laboratory tests.
5. The female subject shows negative pregnancy test results within 30 days prior to the first dose of the study.

6. The Subject did not take any of the following medications in the specified durations:

   • Any medication within 14 days prior to the first dose of the study
   • Any enzyme inducer or inhibitor within 30 days prior to the first dose of the study
7. Subject understood and has signed the written informed consent form.

Exclusion Criteria:

1. Subjects with any properly diagnosed disease within 30 days prior to the first dose of the study.
2. Subjects with a clinically significant hematological, endocrine, cardiovascular, hepatic, renal, gastrointestinal, and/or pulmonary disorder; subjects with any predisposing condition that might interfere with the absorption, distribution, metabolism and excretion of drugs; subjects who has had any previous gastrointestinal surgery, except appendectomy if performed >90 days prior to the first dose of the study
3. Subjects who require treatment with any medications, either prescription or non-prescription (excluding vitamins and food supplements), within 30 days prior to the first dose of the study
4. Subjects who have received any known hepatic or renal clearance-altering agents (e.g., erythromycin, cimetidine, barbiturates, phenothiazine, clarithromycin, trolearndomycin, ketoconazole, miconazole, fluconazole, itraconazole) for a period of up to 30 days prior to the first dose of the study
5. The subject had participated in investigational drug trials and took any investigational drug within 60 days prior to the first dose of the study.
6. The subject had blood donation more than 250 and 500 mL within 60 and 90 days, respectively prior to the first dose of the study.
7. The subject had a history of drug abuse or alcohol abuse.
8. Subjects cannot stop smoking and caffeine-intakes for 48 hours prior to the first dose of the study and during the entire study period.
9. Subjects who are pregnant or lactating
10. For enrollment of female subjects with child-bearing potential, the subject must be practicing sexual abstinence or be using and willing to continue to use a medically acceptable form of birth control for at least 30 days prior to screening (that period will extend to 3 months for oral contraceptive use) and for at least 30 days after the last dose of study drug. For a subject to be considered not to be of child-bearing potential, she must have been amenorrheic for at least 2 years, or must have had a hysterectomy, a bilateral tubal ligation, and/or a bilateral oophorectomy (as determined by the medical history). The male partner of a female study subject with childbearing potential must use a condom and ensure that his partner uses a suitable method of contraception as outlined above.
11. Subjects who are inappropriate to participate in this study, as judged by the medical investigator or sub-investigator
12. Subjects with any contraindication to the use of test medications
13. Subjects who are carriers of hepatitis B virus, hepatitis C virus, or are syphilis (STS) positive, or human immunodeficiency virus (HIV) positive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ibuprofen CR Tablet 600 mg-fasting; One tablet of IBUCR 600 mg under fasting condition	Drug: Ibuprofen CR Tablets 600 mg; Administration of the investigational product: Single oral dose of IBUCR, followed by 28 and 32 hours after the dose administration for fasted and fed studies, respectively; Other Names: Ibuprofen Controlled-Release Tablet 600 mg
Experimental: Ibuprofen CR Tablet 600 mg-fed; One tablet of IBUCR 600 mg under fed condition	Drug: Ibuprofen CR Tablets 600 mg; Administration of the investigational product: Single oral dose of IBUCR, followed by 28 and 32 hours after the dose administration for fasted and fed studies, respectively; Other Names: Ibuprofen Controlled-Release Tablet 600 mg
Active Comparator: Advil Ibuprofen table 200 mg-fasting; IBUAdv with a 4-hour dosing interval for 3 tablets (3×200 mg, q4h) under fasting condition	Drug: Advil Ibuprofen table 200 mg; Administration of the comparator drug: Three tablets (dosing at a 4-hour interval, q4h) of reference ibuprofen standard products, followed by 24 hours after the first dose administration.; Other Names: Advil® Ibuprofen Immediate-Release Tablet 200 mg
Active Comparator: Motrin IB Ibuprofen Tablets 200 mg-fasting; IBUMot with a 4-hour doing interval for 3 tablets (3×200 mg, q4h) under fasting condition	Drug: Motrin IB Ibuprofen Tablets 200 mg; Administration of the comparator drug: Three tablets (dosing at a 4-hour interval, q4h) of reference ibuprofen standard products, followed by 24 hours after the first dose administration.; Other Names: Motrin® IB Ibuprofen Tablets 200 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve from time zero to the time of the last quantifiable plasma concentration of the period (AUC0-last)	The 90% CI for the geometric mean ratios (i.e., antilog-transformation for 90% CI of difference with log transformation) of AUC0-last within [0.8, 1.25] range will be used to determine the result of bioequivalence.	1 month
Area under the curve from time zero to infinity (AUC0-inf)	The 90% CI for the geometric mean ratios (i.e., antilog-transformation for 90% CI of difference with log transformation) of AUC0-inf within [0.8, 1.25] range will be used to determine the result of bioequivalence.	1 month
Peak concentration at each treatment period (Cmax,tp)	The 90% CI for the geometric mean ratios (i.e., antilog-transformation for 90% CI of difference with log transformation) of Cmax,tp within [0.8, 1.25] range will be used to determine the result of bioequivalence.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak concentration of the first dosing (Cmax)	Individual ibuprofen plasma concentration-time profile for each treatment period will be established.	1 month
Time to reach peak concentration of the first dosing (Tmax)	Individual ibuprofen plasma concentration-time profile for each treatment period will be established.	1 month
Terminal half-life (T1/2)	Individual ibuprofen plasma concentration-time profile for each treatment period will be established.	1 month
Mean residence time (MRT)	Individual ibuprofen plasma concentration-time profile for each treatment period will be established.	1 month
The maximum ibuprofen plasma concentration within 1 hour after the first dose administration (Cmax0-1h)	The Cmax0-1h will be observed. The mean Cmax0-1h of test and reference treatments under fasting condition will be calculated. Percentage of the test drug-treated subjects with higher or equal Cmax0-1h compared to that of receiving the reference treatments under fasting condition will be calculated.	0.5h and 1h post-dose
The minimum ibuprofen plasma concentration within a time window of 1-12 hours after the first dose administration (Cmin1-12h)	The Cmin1-12h will be observed. The mean Cmin1-12h of test and reference treatments under fasting condition will be calculated.	1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h and 12h post-dose
The mean time to drop to the Cmin1-12h of reference treatments	For the plasma ibuprofen concentration of test treatments under fasting condition, the mean time to drop to the Cmin1-12h of reference treatments will be calculated.	0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 12h, 18h, 24h, 28h, 32h post-dose
Plasma ibuprofen concentrations at 8-hour (C8h) after the first dose administration	The C8h after the first dose administration will be observed (prior to the 8-hour dose administration for the reference treatments). The mean C8h of test and reference treatments under fasting condition will be calculated.	8-hour after the first dose administration
Plasma ibuprofen concentrations at 12-hour (C12h) after the first dose administration	The C12h after the first dose administration will be observed. The mean C12h of test and reference treatments under fasting condition will be calculated.	12-hour after the first dose administration
Percentage of the test drug-treated subjects with higher or equal C8h compared to that of receiving the reference treatments (before dose 3) under fasting condition		1 month
Percentage of the test drug-treated subjects with higher or equal C12h compared to that of receiving the reference treatments under fasting condition		1 month

Collaborators and Investigators

• Sponsor: Overseas Pharmaceuticals, Ltd.
• Collaborators: Virginia Contract Research Organization Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2017
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: January 25, 2018
• First Posted (Actual): February 1, 2018

Study Record Updates

• Last Update Posted (Actual): April 1, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Ibuprofen; Food Effect; pain control; Controlled-Release
• 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: OVEIBUZ20151221

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No