Bioequivalence Study of Test and Reference 400 mg Ibuprofen Coated Tablets in Healthy Volunteers

Study Overview
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Brief Summary
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This study is a comparative bioavailability study performed to assess bioequivalence between Test medicinal product (Darfen 400, 400 mg ibuprofen coated tablets [512 mg ibuprofen sodium dihydrate], manufactured by PrJSC Pharmaceutical firm Darnitsa [Ukraine]) and Reference medicinal product (marketed medicinal product Nurofen® Forte Express, 400 mg ibuprofen coated tablets [512 mg ibuprofen sodium dihydrate], manufactured by Reckitt Benckiser [Poland] S.A.) in healthy volunteers.

Official Title
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Randomized, Two-way, Two-period, Single Oral Dose, Open-label, Crossover, Bioequivalence Study to Compare Darfen 400, 400 mg Ibuprofen Coated Tablets (512 mg Ibuprofen Sodium Dihydrate) Versus Nurofen® Forte Express, 400 mg Ibuprofen Coated Tablets (512 mg Ibuprofen Sodium Dihydrate) in Healthy Adult Male and Female Subjects Under Fasting Conditions

Conditions
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Bioequivalence, Healthy Subjects

Intervention / Treatment
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* Drug: Darfen 400, 400 mg ibuprofen coated tablets (512 mg ibuprofen sodium dihydrate)
* Drug: Nurofen® Forte Express, 400 mg ibuprofen coated tablets (512 mg ibuprofen sodium dihydrate)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is Caucasian & aged between eighteen to fifty years (18 - 50), both inclusive. The subject is within the limits for his height & weight as defined by the body mass index range (18.5 - 30.0 Kg/m2). The subject is willing to undergo the necessary pre- & post- medical examinations set by this study. The results of medical history, physical examination, vital signs & conducted medical laboratory tests are normal as determined by the clinical investigator. The subject tested negative for Hepatitis B (HBsAg), Hepatitis C (HCVAb), human immunodeficiency virus (HIV Ab). There is no evidence of psychiatric disorder, antagonistic personality, and poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with protocol requirements. The subject is able to understand and willing to sign the informed consent form. For female subjects: a negative pregnancy test must be confirmed, and if sexually active, at least 4 weeks of highly effective contraceptive method must be used prior to IMP administration and throughout the study progress until last visit; highly effective methods comprise hormonal contraceptives, intrauterine devices IUDs, sexual abstinence or vasectomized partner (success of vasectomy was medically proven). For subjects using a hormonal contraceptive method, a barrier form of contraception should be combined with the hormonal contraception. The subject kidney and liver (AST & ALT enzymes) functions tests are within normal range. The subject has normal gastrointestinal, respiratory & cardiovascular systems. Exclusion Criteria: Subject is a smoker or an ex-smoker with a non-smoking history of less than 6 months. The subject has suffered an acute illness one week before dosing. The subject has a history of or concurrent abuse of alcohol. The subject has a history of or concurrent abuse of illicit drugs. The subject has a history of hypersensitivity and/or contraindications to the study drug and any related compounds. The subject has been hospitalized within three months before the study or during the study. The subject is on special diet (for example subject is vegetarian). The subject has consumed caffeine or xanthine containing beverages or foodstuffs within two days before dosing and until 24 hours after dosing in all study periods. The subject has taken a prescription medication within two weeks or even an over-the-counter product (OTC) within one week before dosing in each study period and any time during the study, unless otherwise judged acceptable by the clinical investigator. The subject has taken grapefruit containing beverages or foodstuffs within seven (7) days before first dosing and any time during the study. The subject has been participating in any clinical study (e.g., pharmacokinetics, bioavailability and bioequivalence studies) within the last 80 days prior to the present study. The subject has donated blood within 80 days before first dosing. The subject has a history or presence of cardiovascular, pulmonary, renal, hepatic, gastrointestinal, hematological, endocrinal, immunological, dermatological, neurological, musculoskeletal or psychiatric diseases. The subject has consumed drugs that may affect pharmacological or pharmacokinetic properties of Ibuprofen (for example: aspirin, celecoxib, ciprofloxacin, diclofenac, etodolac, fish oil, heparin, ketorolac, ketoprofen, naproxen, rivaroxaban, vitamin B12, vitamin C and vitamin D3) two weeks before dosing, during the study and two weeks after dosing. Pregnant; with positive serum pregnancy test or breast-feeding female subjects. The subject has a history of, or active, peptic ulceration, gastritis, esophagitis, gastrointestinal bleeding or perforation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Two-period, two-sequence, two-way crossover single dose study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Darfen 400<br>A single oral dose of the test product Darfen 400, 400 mg ibuprofen coated tablets (512 mg ibuprofen sodium dihydrate) | Drug: Darfen 400, 400 mg ibuprofen coated tablets (512 mg ibuprofen sodium dihydrate)<br>* Oral, a nonsteroidal anti-inflammatory drug<br>|
| Active Comparator: Nurofen® Forte Express<br>A single oral dose of the reference product Nurofen® Forte Express, 400 mg ibuprofen coated tablets (512 mg ibuprofen sodium dihydrate) | Drug: Nurofen® Forte Express, 400 mg ibuprofen coated tablets (512 mg ibuprofen sodium dihydrate)<br>* Oral, a nonsteroidal anti-inflammatory drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | The Cmax value is based on the ibuprofen plasma concentration. | Blood sampling for pharmacokinetic analysis covered up to 24 hours post-dose | 
| Area under the concentration-time curve from time zero to the last quantifiable concentration (t) | The AUC0-t is the area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (t) and is based on the ibuprofen plasma concentration. | Blood sampling for pharmacokinetic analysis covered up to 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy subjects, ibuprofen, pharmacokinetics, bioequivalence