Bioequivalence Study to Compare Diclofenac Potassium Coated Tablet Versus Cataflam® 50 Coated Tablet

Study Overview
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Brief Summary
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Randomized, four-way, four-period, fully-replicated, single oral dose, open-label, crossover, bioequivalence study to compare Diclofenac Potassium coated tablet (50 mg Diclofenac Potassium) versus Cataflam® 50 coated tablet (50 mg Diclofenac Potassium), in healthy subjects under fasting condition

Official Title
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Randomized,Fully-replicated,Single Oral Dose,Open-label,Crossover BE Study to Compare Diclofenac Potassium Coated Tablet (50 mg Diclofenac Potassium) Versus Cataflam® 50 Coated Tablet (50 mg Diclofenac Potassium) in Healthy Subjects in Fasting State

Conditions
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Non-steroidal Anti-inflammatory (NSAID), Analgesic, Antipyretic

Intervention / Treatment
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* Drug: Diclofenac Potassium coated tablet (50 mg Diclofenac Potassium)
* Drug: Cataflam® 50 coated tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is aged between eighteen & fifty years (18 - 50). 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, vital signs, physical examination & conducted medical laboratory tests are normal as determined by the clinical investigator. The subject tested negative for hepatitis (B & C) viruses and Human Immunodeficiency Virus (HIV). 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: negative pregnancy test and the woman is using two reliable contraception methods. The subject has normal gastrointestinal, cardiovascular system and ECG recording. The subject kidney and liver (AST & ALT enzymes) functions tests are within normal range. Exclusion Criteria: The subject is a heavy smoker (more than 10 cigarettes per day). 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 vegetarian. The subject has consumed caffeine or xanthine containing beverages or foodstuffs within two days before dosing and until 10 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 (Voriconazole and Aspirin) two weeks before dosing, during the study and two weeks after dosing.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diclofenac Potassium coated tablet (50 mg Diclofenac Potassium)<br> | Drug: Diclofenac Potassium coated tablet (50 mg Diclofenac Potassium)<br>* One Diclofenac tablet was administered orally.<br>Drug: Cataflam® 50 coated tablet<br>* One Diclofenac tablet was administered orally.<br>|
| Active Comparator: Cataflam® 50 coated tablet (50 mg Diclofenac Potassium)<br> | Drug: Diclofenac Potassium coated tablet (50 mg Diclofenac Potassium)<br>* One Diclofenac tablet was administered orally.<br>Drug: Cataflam® 50 coated tablet<br>* One Diclofenac tablet was administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) | Statistical analysis of primary endpoints will include descriptive statistics, Analysis of Variance (ANOVA), and Confidence Interval (CI). The average bioequivalence of the products is concluded if the two-sided 90 % CI for the test to reference ratio of the population means is within 80.00 - 125.00 % for each of the Ln-transformed data for Cmax | 10 hours | 
| AUC0-t | Statistical analysis of primary endpoints will include descriptive statistics, Analysis of Variance (ANOVA), and Confidence Interval (CI). The average bioequivalence of the products is concluded if the two-sided 90 % CI for the test to reference ratio of the population means is within 80.00 - 125.00 % for each of the Ln-transformed data for AUC0-t | 10 hours | 
| AUC0-∞ | Statistical analysis of primary endpoints will include descriptive statistics, Analysis of Variance (ANOVA), and Confidence Interval (CI). The average bioequivalence of the products is concluded if the two-sided 90 % CI for the test to reference ratio of the population means is within 80.00 - 125.00 % for each of the Ln-transformed data for AUC0-∞ | 10 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | The descriptive statistics including Maximum, Minimum and Median values will be measured for Tmax | 10 hours | 
| Thalf | Thalf was calculated from 0.693/ λz | 10 hours | 
| Kelimination | The terminal elimination rate constant (Kelimination or λz) was estimated for each subject and for each treatment via linear regression of the last points (at least three points will be used) at the terminal phase of the log-concentration versus time curve of each subject | 10 hours | 
| Blood pressure (safety and tolerability) | Clinically significant abnormal deviations. Normal range of blood pressure > 90/60 and <140/90 mmHg. | At pre-dosing, 2, 4, 6, 8, and 10 hours post dosing, ± 45 minutes of scheduled time | 
| Pulse (safety and tolerability) | Clinically significant abnormal deviations. Normal range of Pulse 60-100 bpm. | At pre-dosing, 2, 4, 6, 8, and 10 hours post dosing, ± 45 minutes of scheduled time | 
| Temperature(safety and tolerability) | Clinically significant abnormal deviations. Normal range of temperature 36.5-37.5 ºC. | At pre-dosing; 4, and 10 hours post dosing, ± 45 minutes of scheduled time |