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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

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ClinicalTrials.gov Identifier: NCT03418805
Recruitment Status : Suspended (Sponsor's consideration of product development strategies)
First Posted : February 1, 2018
Last Update Posted : August 22, 2018
Sponsor:
Information provided by (Responsible Party):
Overseas Pharmaceuticals, Ltd.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Pain Control Drug: Advil Ibuprofen table 200 mg Drug: Motrin IB Ibuprofen Tablets 200 mg Drug: Ibuprofen CR Tablets 600 mg Phase 1

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)


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: 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
Actual Study Start Date : December 11, 2017
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 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 Name: Motrin® IB Ibuprofen Tablets 200 mg




Primary Outcome Measures :
  1. Area under the curve from time zero to the time of the last quantifiable plasma concentration of the period (AUC0-last) [ Time Frame: 1 month ]
    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.

  2. Area under the curve from time zero to infinity (AUC0-inf) [ Time Frame: 1 month ]
    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.

  3. Peak concentration at each treatment period (Cmax,tp) [ Time Frame: 1 month ]
    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.


Secondary Outcome Measures :
  1. Peak concentration of the first dosing (Cmax) [ Time Frame: 1 month ]
    Individual ibuprofen plasma concentration-time profile for each treatment period will be established.

  2. Time to reach peak concentration of the first dosing (Tmax) [ Time Frame: 1 month ]
    Individual ibuprofen plasma concentration-time profile for each treatment period will be established.

  3. Terminal half-life (T1/2) [ Time Frame: 1 month ]
    Individual ibuprofen plasma concentration-time profile for each treatment period will be established.

  4. Mean residence time (MRT) [ Time Frame: 1 month ]
    Individual ibuprofen plasma concentration-time profile for each treatment period will be established.

  5. The maximum ibuprofen plasma concentration within 1 hour after the first dose administration (Cmax0-1h) [ Time Frame: 0.5h and 1h post-dose ]
    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.

  6. The minimum ibuprofen plasma concentration within a time window of 1-12 hours after the first dose administration (Cmin1-12h) [ Time Frame: 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h and 12h post-dose ]
    The Cmin1-12h will be observed. The mean Cmin1-12h of test and reference treatments under fasting condition will be calculated.

  7. The mean time to drop to the Cmin1-12h of reference treatments [ Time Frame: 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 12h, 18h, 24h, 28h, 32h post-dose ]
    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.

  8. Plasma ibuprofen concentrations at 8-hour (C8h) after the first dose administration [ Time Frame: 8-hour 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.

  9. Plasma ibuprofen concentrations at 12-hour (C12h) after the first dose administration [ Time Frame: 12-hour 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.

  10. 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 [ Time Frame: 1 month ]
  11. Percentage of the test drug-treated subjects with higher or equal C12h compared to that of receiving the reference treatments under fasting condition [ Time Frame: 1 month ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03418805


Locations
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Taiwan
Tri-Service General Hospital
Taipei, Taiwan
Sponsors and Collaborators
Overseas Pharmaceuticals, Ltd.

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Responsible Party: Overseas Pharmaceuticals, Ltd.
ClinicalTrials.gov Identifier: NCT03418805     History of Changes
Other Study ID Numbers: OVEIBUZ20151221
First Posted: February 1, 2018    Key Record Dates
Last Update Posted: August 22, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Overseas Pharmaceuticals, Ltd.:
Ibuprofen
Controlled-Release
pain control
Healthy Volunteers
Food Effect
Additional relevant MeSH terms:
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Ibuprofen
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action