Effect of Riociguat on Bone Metabolism

Clinical pharmacology

Inclusion criteria

• Healthy male white subjects
• 18 to 45 years of age
• BMI between 18 and 28 kg/m2
• Subjects who are able to understand and follow instructions and who are able to participate in the study for the entire period

Exclusion criteria

• Relevant deviation from the normal range in the clinical examination; in clinical chemistry, hematology, or urinalysis
• Resting heart rate in the awake subject below 45 BPM or above 90 BPM
• Systolic blood pressure below 100 mmHg or above 145 mmHg
• Diastolic blood pressure above 95 mmHg
• Relevant pathological changes in the ECG such as a second or third-degree AV block, prolongation of the QRS complex over 120 msec or of the QT / QTc-interval over 450 msec for males
• History of genetic muscle or bone disease of any kind
• Completely sedentary or extremely fit subjects
• Fractures in the preceding 12 months
• Psychiatric diseases
• History of peptic ulcers or relevant gastro-esophageal reflux disease
• Subjects with hypersensitivity to the investigational drug riociguat or ranitidine, or to inactive constituents
• Regular daily consumption of more than half a liter of usual beer or the equivalent quantity of approximately 20 g of alcohol in another form, more than 1 L of xanthine-containing beverages, recent smoking history
• Use of medication within the 2 weeks preceding the study which could have interfered with the investigational drug riociguat or ranitidine
• Subjects with a medical disorder, condition or history of such that would have impaired the subject's ability to participate or complete this study in the opinion of the investigator or the sponsor