MedPath

To Evaluate the Food Effect and the Absorption Profile of Ibuprofen Modified-Release Tablets 800 mg

Phase 1
Completed
Conditions
Chronic Pain
Interventions
Registration Number
NCT05329454
Lead Sponsor
Overseas Pharmaceuticals, Ltd.
Brief Summary

An open-label, randomized, 3-way crossover study to evaluate the pharmacokinetics of investigational product "Ibuprofen Modified-Release Tablets 800 mg" in comparison to the reference standard "Ibuprofen Regular-Release Tablets 600 mg/800 mg" in normal healthy volunteers

Primary objective:

To evaluate the food effect of IBUMR and its bioavailability of single and multiple doses compared with reference drugs in normal healthy volunteers.

Secondary objectives:

1. To determine and compare the single and multiple dose PK profiles of IBUMR and reference drugs.

2. To identify the effect duration for IBUMR after dose administration by detecting ibuprofen concentrations in plasma.

3. To evaluate the safety profile of single and multiple doses of IBUMR.

Detailed Description

This study consists of 3 treatment periods as below. For Treatment A and Treatment B, single- and multiple-dose stages are included.

Treatment A:

One tablet of IBUMR will be administered to the subjects under fasted condition, followed by a minimum of 72-hour washout interval. After the washout period, subjects will receive 1 × IBUMR every 12 hours for a total of 8 doses.

Treatment B:

One tablet of IBURed-800mg will be administered to the subjects under fasted condition, followed by a minimum of 72-hour washout interval. After the washout period, subjects will receive 1 × IBURed-600mg every 8 hours for a total of 12 doses.

Treatment C:

Single dose of IBUMR will be given to the subjects under fed condition (a standard high-fat, high calorie breakfast should be consumed within 30 minutes prior to dosing).

A minimum of 3-day washout interval will be introduced across the 3 treatment periods. Subjects will be required to be fasted for at least 10 hours prior to the administration of morning doses.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
Inclusion Criteria
  • 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.

  • Subject's medical history shows no contraindication to the test medications (hypersensitivity to ibuprofen or any component of test and reference products) and non-steroidal anti-inflammatory drugs (NSAIDs).
  • Subjects who are judged to be in good health by the investigator based upon the results of physical examination (PE), vital signs, and routine laboratory tests.
  • The female subject shows negative pregnancy test results within 30 days prior to the first dose of the study.
  • The subject did not take any of the following medications in the specified durations:
  • Any systemically absorbed medication within 14 days (excluding vitamins, food supplements and hormone contraceptives not ibuprofen drug interactions) prior to the first dose of the study
  • Any enzyme inducer/inhibitor and/or known hepatic or renal clearance-altering agents (e.g., erythromycin, cimetidine, barbiturates, phenothiazine, clarithromycin, troleandomycin, ketoconazole, miconazolem fluconazole, itraconazole) within 30 days prior to the first dose of the study.
  • Subjects are willing to comply with protocol-stated requirements, instructions and restrictions, followed by understanding and signing the written informed consent form by the subject or legal representative if he/she is under the statutory age of consent as per the local authority.
Exclusion Criteria
  • Subjects with any properly diagnosed disease within 30 days prior to the first dose of the study.
  • 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 or coronary artery bypass graft.
  • 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
  • Subjects have participated in investigational drug trials and took any investigational drug within 60 days prior to the first does of the study.
  • Subjects had blood donation more than 250 and 500 mL within 60 and 90 days, respectively prior to the first dose of the study.
  • Subjects had a history of drug abuse or alcohol abuse according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria.
  • Subjects cannot stop smoking and caffeine-intakes for 48 hours prior to the first dose of the study and during the entire study period.
  • Subjects who are pregnant or lactating.
  • Subjects who have been tested positive for the following tests:
  • Human immunodeficiency virus (HIV)
  • Hepatitis B virus (HBV)
  • Hepatitis C virus (HCV)
  • Treponema pallidum (STS test)
  • 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.
  • Subjects with underlying medical, mental, psychological, or other inappropriate conditions that would impair treatment compliance, or in the opinion of the investigator would not permit to participate in the study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Treatment ACBIbuprofen TabletsReceive the investigational product and active comparator in a sequence of treatment A, treatment C and treatment B.
Treatment ABCIbuprofen TabletsReceive the investigational product and active comparator in a sequence of treatment A, treatment B and treatment C.
Treatment BACIbuprofen TabletsReceive the investigational product and active comparator in a sequence of treatment B, treatment A and treatment C.
Treatment CABIbuprofen TabletsReceive the investigational product and active comparator in a sequence of treatment C, treatment A and treatment B.
Treatment BCAIbuprofen TabletsReceive the investigational product and active comparator in a sequence of treatment B, treatment C and treatment A.
Treatment CBAIbuprofen TabletsReceive the investigational product and active comparator in a sequence of treatment C, treatment B and treatment A.
Primary Outcome Measures
NameTimeMethod
To evaluate the food effects of IBUMR on PK parametersAfter collecting blood samples from the last participant, up to 30 days

To assess the food effect of IBUMR in the PK parameters including AUCL

Comparison of single-dose and multi-dose bioavailability of IBUMR and IBURedAfter collecting blood samples from the last participant, up to 30 days

Comparison of single-dose and multiple-dose bioavailability between IBUMR and IBURed in log-transformed values of the peak concentration (Cmax)

Comparison of single - and multi-dose bioavailability of IBUMR and IBURedAfter collecting blood samples from the last participant, up to 30 days

Comparison of single-dose and multiple-dose bioavailability between IBUMR and IBURed in log-transformed values of area under the curve from time 0 to infinity (AUCinf).

To assess the food effect of IBUMR in the PK parametersAfter collecting blood samples from the last participant, up to 30 days

To assess the food effect of IBUMR in the PK parameters including Cmax

To evaluate the food effect of IBUMR on PK parametersAfter collecting blood samples from the last participant, up to 30 days

To assess the food effect of IBUMR in the PK parameters including time to reach peak concentration (Tmax)

Evaluate the food effect of IBUMR in PK parametersAfter collecting blood samples from the last participant, up to 30 days

To assess the food effect of IBUMR in the PK parameters including AUCinf

Comparison of single-dose and multiple-dose bioavailability between IBUMR and IBURedAfter collecting blood samples from the last participant, up to 30 days

Comparison of single-dose and multiple-dose bioavailability between IBUMR and IBURed in log-transformed values of area under the curve from time 0 to the last measurable concentration (AUCL)

Determine the food effect of IBUMR in PK parametersAfter collecting blood samples from the last participant, up to 30 days

To assess the food effect of IBUMR in the PK parameters including elimination half-life (t1/2)

Secondary Outcome Measures
NameTimeMethod
Single dose PK stepAfter collecting blood samples from the last participant, up to 30 days

-- Elimination half-life (t1/2)

Single dose PKAfter collecting blood samples from the last participant, up to 30 days

-- Area under the concentration-time curve extrapolated from the last detectable sampling time point to infinity as a percentage of total AUC (AUCextrap)

Incidence of sudden adverse events (safety and tolerability)After collecting blood samples from the last participant, up to 60 days

abnormal laboratory tests results

Single-dose PK measuresAfter collecting blood samples from the last participant, up to 30 days

-- Time to reach peak concentration (Tmax)

Single dose PK designAfter collecting blood samples from the last participant, up to 30 days

-- Apparent oral clearance (CL/F)

Multiple - dosed PKAfter collecting blood samples from the last participant, up to 30 days

-- Plasma drug concentration at a specified time t steady state (Ct,ss)

Multiple - dosed PK stepsAfter collecting blood samples from the last participant, up to 30 days

-- Trough plasma concentration at steady state (Ctrough)

Multiple - dosed PK methodAfter collecting blood samples from the last participant, up to 30 days

-- Average concentration at steady state (Cavg)

Multiple - dosed PK programAfter collecting blood samples from the last participant, up to 30 days

-- AUC in 1 dosing interval (AUCτ) at steady state

Evaluation of duration of IBUMR effectAfter collecting blood samples from the last participant, up to 30 days

-- Percentage of the test drug-treated subjects with higher or equal plasma ibuprofen concentrations at 12-hour at steady state (C12,ss) compared to the Ctrough of IBURed-600mg will be calculated.

Incidence of treatment-emergent adverse events (safety and tolerability)After collecting blood samples from the last participant, up to 60 days

Incidence of AEs and SAEs

Single dose PK methodAfter collecting blood samples from the last participant, up to 30 days

-- Area under the concentration-time curve within time span t1 to t2 (AUCt1→t2)

Multiple-dose PK measuresAfter collecting blood samples from the last participant, up to 30 days

-- Peak concentration at steady state (Cmax,ss)

Multiple - dosed PK planAfter collecting blood samples from the last participant, up to 30 days

-- Area under the concentration-time curve within time span t1 to t2 at steady state (AUCt1→t2,ss)

Multiple - dosed PK arrangementAfter collecting blood samples from the last participant, up to 30 days

-- Apparent oral clearance at steady state (CL/Fss)

Multiple - dosed PK planningAfter collecting blood samples from the last participant, up to 30 days

-- Apparent volume of distribution after oral administration at steady state (Vd/Fss)

Assessment of effect duration for IBUMRAfter collecting blood samples from the last participant, up to 30 days

-- For the plasma ibuprofen concentration of IBUMR at steady state, the time to drop to the Ctrough of IBURed-600mg will be calculated.

safety and tolerabilityAfter collecting blood samples from the last participant, up to 60 days

incidence of abnormal Physical examination

Incidence of treatment-induced adverse events (safety and tolerability)After collecting blood samples from the last participant, up to 60 days

abnormal 12-lead ECG exams

Single dose PK movesAfter collecting blood samples from the last participant, up to 30 days

-- Apparent volume of distribution after oral administration (Vd/F)

Multiple - dosed PK designAfter collecting blood samples from the last participant, up to 30 days

-- Time to reach peak concentration at steady state (Tmax,ss)

Multiple - dosed PK processAfter collecting blood samples from the last participant, up to 30 days

-- Terminal half-life at steady state (t1/2,ss)

Incidence of treatment-emergent adverse eventsAfter collecting blood samples from the last participant, up to 60 days

abnormal Vital signs

Trial Locations

Locations (1)

Taipei Medical University Hospital

🇨🇳

Taiwan, China

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