Pharmacology, Clinical
Conditions
Keywords
Bone Metabolism
Brief summary
Investigation of the effect of Riociguat, administered as 2.5 mg IR-tablets TID over 14 days, on bone metabolism.
Detailed description
Clinical pharmacology
Interventions
DRUGRiociguat (Adempas, BAY63-2521) immediate release tablet of 2.5 mg
Riociguat administered in a dose of 2.5 mg (single tablet), thrice daily, over 14 days.
DRUGPlacebo
Placebo administered as a single tablet, thrice daily, over 14 days.
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary excretion (over 24 hours) of C-terminal cross-linking telopeptides of type I collagen (CTX) | From Day -01 to 16 | Marker of bone resorption |
| AUC(0-7) | Pre-dose and up to 7 hours post-dose on Day 0 | Area under the plasma concentration vs time curve (AUC) from zero to 7 hours after single (first) dose for riociguat and its metabolite M-1 (BAY60-4552) |
| AUC(0-7)ss | Pre-dose and up to 7 hours post-dose on Day 13 | AUC(0-7) at steady state |
| Cmax | Pre-dose and up to 7 hours post-dose on Day 0 | Maximum drug concentration in plasma after single dose administration for riociguat and its metabolite M-1 (BAY60-4552) |
| Cmax,ss | Pre-dose and up to 7 hours post-dose on Day 13 | Maximum drug concentration in plasma at steady state during a dosage interval for riociguat and its metabolite M-1 (BAY60-4552) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax,ss,norm | Pre-dose and up to 7 hours post-dose on Day 13 | Maximum drug concentration in plasma at steady state during a dosage interval divided by dose (mg) per kg body weight for riociguat and its metabolite M-1 (BAY60-4552) |
| tmax | Pre-dose and up to 7 hours post-dose on Day 0 | Time to reach maximum drug concentration in plasma after single (first) dose for riociguat and its metabolite M-1 (BAY60-4552) |
| tmax,ss | Pre-dose and up to 7 hours post-dose on Day 13 | tmax at steady state for riociguat and its metabolite M-1 (BAY60-4552) |
| Aeur(0-7) | Pre-dose and up to 7 hours post-dose | Amount of drug excreted via urine from zero to 7 hours after administration for riociguat and its metabolite M-1 (BAY60-4552) |
| %Aeur(0-7) | Pre-dose and up to 7 hours post-dose | Aeur(0-7) expressed as percent of dose administered for riociguat and its metabolite M-1 (BAY60-4552) |
| Urinary excretion (over 24 hours) of N-terminal cross-linking telopeptides of type I collagen (NTX) | From -01 to 16 Days | Marker of bone resorption |
| Serum CTX | From -01 to 16 Days | Marker of bone resorption |
| Serum N-terminal propeptide of type I collagen (PINP) | From -01 to 16 Days | Marker of bone formation |
| Serum bone-specific alkaline phosphatase (bAP) | From -01 to 16 Days | Marker of bone formation |
| Number of participants with adverse events | Approximately 12 weeks | — |
| Cyclic guanosine monophosphate (cGMP) | From -01 to 16 Days | Determination of cGMP in plasma and urinary excretion (over 24 hours) |
| Calcium, sodium, potassium | From -01 to 16 Days | Determination of calcium, sodium, potassium in serum and urinary excretion (over 24 hours) |
| Urine volume | From -01 to 16 Days | Volume of urine excreted (over 24 hours) |
| Renin | From -01 to 16 Days | Determination of plasma renin level |
| Creatinine clearance | From -01 to 16 Days | For estimation of glomerular filtration rate |
| Serum osteocalcin | From -01 to 16 Days | Determination of osteocalcin in serum |
| Creatinine | From -01 to 16 Days | Determination of creatinine in serum and urinary excretion (over 24 hours) |
| Phosphate | From -01 to 16 Days | Determination of phosphate in serum only |
| Parathyroid hormone (PTH) | From -01 to 16 Days | Determination of PTH in serum only |
| Serum albumin, protein | From -01 to 16 Days | Determination of albumin, protein in serum |
| Ctrough | On Days 03 and 08 | Drug concentration in plasma at expected time of minimum (trough) concentration for riociguat and its metabolite M-1 (BAY60-4552) |
| AUC(0-7)norm | Pre-dose and up to 7 hours post-dose on Day 0 | AUC(0-7) divided by dose per kg body weight for riociguat and its metabolite M-1 (BAY60-4552) |
| AUC(0-7)ss,norm | Pre-dose and up to 7 hours post-dose on Day 13 | AUC(0-7)ss divided by dose per kg body weight for riociguat and its metabolite M-1 (BAY60-4552) |
| Cmax,norm | Pre-dose and up to 7 hours post-dose on Day 0 | Maximum drug concentration in plasma after (first) single dose administration divided by dose (mg) per kg body weight for riociguat and its metabolite M-1 (BAY60-4552) |
Countries
Germany
Outcome results
None listed