Bioequivalence Study to Compare Chenodeoxycholic Acid Capsules (250mg Chenodeoxycholic Acid) Versus Chenodeoxycholic Acid Leadiant 250 mg Hard Capsules (250mg Chenodeoxycholic Acid)

Study Overview
=================
Brief Summary
-----------------
Randomized, two-way, two-period, single oral dose, open-label, crossover, bioequivalence study to compare Chenodeoxycholic acid capsules (250mg chenodeoxycholic acid) [dose: 1 x 02 capsules] versus Chenodeoxycholic acid leadiant 250 mg hard capsules (250mg chenodeoxycholic acid) [dose: 1 x 02 capsules] in healthy subjects under fasting conditions.

Official Title
-----------------
Randomized, Two-way, Two-period, Single Oral Dose, Open-label, Crossover, Bioequivalence Study to Compare Chenodeoxycholic Acid Capsules (250mg Chenodeoxycholic Acid) [Dose: 1 x 02 Capsules] Versus Chenodeoxycholic Acid Leadiant 250 mg Hard Capsules (250mg Chenodeoxycholic Acid) [Dose: 1 x 02 Capsules] in Healthy Subjects Under Fasting Conditions

Conditions
-----------------
Cerebrotendinous Xanthomatoses

Intervention / Treatment
-----------------
* Drug: Chenodeoxycholic acid
* Drug: Chenodeoxycholic acid leadiant


Participation Criteria
=================
Eligibility Criteria
-----------------
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 - 25.0 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 (HBsAg), Hepatitis C (HCVAb) and human immunodeficiency virus (HIVAb). 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 serum pregnancy test and the woman is using a reliable contraception method. The subject has normal cardiovascular system & ECG recording. The subject kidney and liver (aminotransferase & Alanine transaminase enzymes) functions tests are within normal range. (Creatinine is accepted if below the reference range after being evaluated by the CI as clinically not significant). The subject has normal Triglyceride (0.1-150 mg/dl), HDL (35-55 mg/dl), LDL (0.1-159 mg/dl) and Total Cholesterol levels (0.1-200 mg/dl) or clinical insignificant based on CI evaluation. 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; including its excipients 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 72 hours after dosing in both 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/orange 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. Subject has consumed medicines or foodstuff that may affect pharmacological or pharmacokinetic properties of chenodeoxycholic acid (for example: Antacids (aluminum containing), Bile acid sequestrants such as (cholestyramine or colestipol), Clofibrate, Coumarin-derivative anticoagulants, Estrogens & oral contraceptive) two weeks before dosing, during the study and two weeks after dosing.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chenodeoxycholic acid capsules<br>Chenodeoxycholic acid capsules (250mg chenodeoxycholic acid) | Drug: Chenodeoxycholic acid<br>* Two capsules were administered orally<br>|
| Active Comparator: Chenodeoxycholic acid leadiant hard capsules<br>Chenodeoxycholic acid leadiant hard capsules (250mg chenodeoxycholic acid) | Drug: Chenodeoxycholic acid leadiant<br>* Two capsules were administered orally<br>|

What is the study measuring?
-----------------
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 | 72 hours | 
| Area under the plasma concentration-time curve from time 0 to 12 hours (AUC0-12) | 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 AUC0-12 | 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve from time 0 to 72 hours (AUC0-72) | The descriptive statistics for AUC0-72 | 72 hours |