Bioequivalence Study of Riociguat 2.5 mg Film Coated Tablets and Adempas (Riociguat) 2.5 mg Film Coated Tablets

Study Overview
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Brief Summary
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Single dose oral bioequivalence study of Riociguat 2.5 mg film coated tablets and 'Adempas' (Riociguat) 2.5 mg Filmtabletten (film coated tablets) in healthy adult male subjects under fasting conditions.

Official Title
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Single Dose Oral Bioequivalence Study of Riociguat 2.5 mg Film Coated Tablets and 'Adempas' (Riociguat) 2.5 mg Filmtabletten (Film Coated Tablets) in Healthy Adult Male Subjects Under Fasting Conditions

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Riociguat film coated tablets
* Drug: Adempas Filmtabletten


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteers must fulfill all of the following inclusion criteria to be eligible for participation in the study, unless otherwise specified. 1) Age: 18 to 45 years old, both inclusive. 2) Gender: Male BMI: 18.5 to 30.0 kg/m2, both inclusive; BMI value should be rounded off to one significant digit after decimal point (e.g. 30.04 rounds down to 30.0, while 18.45 rounds up to 18.5). Able to communicate effectively with study personnel. Willing to provide written informed consent to participate in the study. Non-smokers and non-tobacco users (i.e. having no past history of smoking and tobacco consuming for at least one year prior to study). Volunteer must have sitting systolic blood pressure at least 100 mmHg and sitting diastolic blood pressure at least 60 mmHg during screening. Volunteer must agree to either abstain from sexual intercourse or use an acceptable method of birth control from screening until 4 weeks after the last study procedure. All volunteers must be judged by the principal or sub-investigator or physician as normal and healthy during a pre-study safety assessment performed within 28 days of the first dose of study medication which will include: A physical examination (clinical examination) with no clinically significant finding. Results within normal limits or clinically non-significant for the following tests: Hematology, Biochemistry, Urinalysis, Immunological Tests Additional tests and/or examinations (apart from mentioned in protocol) may be performed, if necessary, based on principal investigator discretion. All results will be assessed against the current laboratory normal ranges at the time of testing and a copy of the normal ranges used will be included in the study documentation. Exclusion Criteria: Volunteers must not be enrolled in the study if they meet any one of the following criteria: History of allergic responses to Riociguat or other related drugs, or any of its formulation ingredients. Have significant diseases or clinically significant abnormal findings during screening [medical history, physical examination (clinical examination), laboratory evaluations, ECG recording]. Any disease or condition like diabetes, psychosis or others, which might compromise the haemopoietic, gastrointestinal, renal, hepatic, cardiovascular, respiratory, central nervous system or any other body system. History or presence of bronchial asthma. Use of any hormone replacement therapy within 3 months prior to the first dose of study medication. A depot injection or implant of any drug within 3 months prior to the first dose of study medication. Use of CYP enzyme inhibitors or inducers within 30 days prior to the first dose of study medication (see https://drug-interactions.medicine.iu.edu/MainTable.aspx). History or evidence of drug dependence or of alcoholism or of moderate alcohol use. History of difficulty with donating blood or difficulty in accessibility of veins. A positive hepatitis screen (includes subtypes B & C). A positive test result for HIV antibody. Volunteers who have received a known investigational drug within seven elimination half-life of the administered drug prior to the first dose of study medication. Volunteers who have donated blood or loss of blood 50 ml to 100 ml within 30 days or 101 ml to 200 ml within 60 days or >200 ml within 90 days (excluding volume drawn at screening for this study) prior to first dose of study medication, whichever is greater. History of difficulty in swallowing or of any gastrointestinal disease, which could affect drug absorption. Intolerance to venipuncture Any food allergy, intolerance, restriction or special diet that, in the opinion of the principal investigator or sub-investigator, could contraindicate the volunteer's participation in this study. Institutionalized volunteers. Use of any prescribed medications [including PDE5 inhibitors (such as sildenafil, tadalafil, vardenafil, nitrates or nitric oxide donors (such as amyl nitrite), soluble guanylate cyclase stimulators] within 14 days prior to the first dose of study medication. Use of any OTC products, vitamin and herbal products, etc., within 7 days prior to the first dose of study medication. Use of grapefruit and grapefruit containing products within 7 days prior to the first dose of study medication. Ingestion of any caffeine or xanthine products (i.e. coffee, tea, chocolate, and caffeinecontaining sodas, colas, etc.), recreational drugs (including poppers), alcohol or other alcohol containing products within 120 hours prior to the first dose of study medication. Ingestion of any unusual diet, for whatever reason (e.g.: low sodium) for three weeks prior to the first dose of study medication. Volunteer having serum creatinine higher than upper limit of normal range in screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Riociguat film coated tablets<br>Riociguat 2.5 mg film coated tablets | Drug: Riociguat film coated tablets<br>* 1 tablet of 2.5 mg Riociguat<br>Drug: Adempas Filmtabletten<br>* 1 tablet of 2.5 mg Riociguat<br>|
| Active Comparator: Adempas Filmtabletten<br>Adempas (Riociguat) 2.5 mg Filmtabletten | Drug: Riociguat film coated tablets<br>* 1 tablet of 2.5 mg Riociguat<br>Drug: Adempas Filmtabletten<br>* 1 tablet of 2.5 mg Riociguat<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration obtained (Cmax) | Two-sided 90% confidence interval for the test to reference ration of the population means is within 80.00% to 125.00% for each of the Ln-transformed data Cmax | 48 hours | 
| AUC from time 0 to last collection time t (AUC) | Two-sided 90% confidence interval for the test to reference ration of the population means is within 80.00% to 125.00% for each of the Ln-transformed data AUC0-t | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC from time 0 to infinity (AUC0-inf) | Descriptive statistics | 48 hours | 
| Time to reach maximum concentration Cmax (Tmax) | Descriptive statistics | 48 hours |