Clinical trial NCT00855660: Effect of Riociguat on Bone Metabolism
Official title: Investigation of the Effect of Riociguat, Administered as 2.5 mg IR-tablets TID Over 14 Days, on Bone Metabolism in a Randomized, Placebo-controlled, Double-blind, 2-fold Cross-over Design in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacology, Clinical
Keywords: Bone Metabolism
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2009-03-04
Enrollment: 17
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Urinary excretion (over 24 hours) of C-terminal cross-linking telopeptides of type I collagen (CTX)
timeFrame: From Day -01 to 16
measure: AUC(0-7)
timeFrame: Pre-dose and up to 7 hours post-dose on Day 0
measure: AUC(0-7)ss
timeFrame: Pre-dose and up to 7 hours post-dose on Day 13
measure: Cmax
timeFrame: Pre-dose and up to 7 hours post-dose on Day 0
measure: Cmax,ss
timeFrame: Pre-dose and up to 7 hours post-dose on Day 13
Secondary outcomes:
measure: Number of participants with adverse events
timeFrame: Approximately 12 weeks
measure: Ctrough
timeFrame: On Days 03 and 08
measure: AUC(0-7)norm
timeFrame: Pre-dose and up to 7 hours post-dose on Day 0
measure: AUC(0-7)ss,norm
timeFrame: Pre-dose and up to 7 hours post-dose on Day 13
measure: Cmax,norm
timeFrame: Pre-dose and up to 7 hours post-dose on Day 0
measure: Cmax,ss,norm
timeFrame: Pre-dose and up to 7 hours post-dose on Day 13
measure: tmax
timeFrame: Pre-dose and up to 7 hours post-dose on Day 0
measure: tmax,ss
timeFrame: Pre-dose and up to 7 hours post-dose on Day 13
measure: Aeur(0-7)
timeFrame: Pre-dose and up to 7 hours post-dose
measure: %Aeur(0-7)
timeFrame: Pre-dose and up to 7 hours post-dose
measure: Urinary excretion (over 24 hours) of N-terminal cross-linking telopeptides of type I collagen (NTX)
timeFrame: From -01 to 16 Days
measure: Serum CTX
timeFrame: From -01 to 16 Days
measure: Serum N-terminal propeptide of type I collagen (PINP)
timeFrame: From -01 to 16 Days
measure: Serum bone-specific alkaline phosphatase (bAP)
timeFrame: From -01 to 16 Days
measure: Serum albumin, protein
timeFrame: From -01 to 16 Days
measure: Cyclic guanosine monophosphate (cGMP)
timeFrame: From -01 to 16 Days
measure: Calcium, sodium, potassium
timeFrame: From -01 to 16 Days
measure: Urine volume
timeFrame: From -01 to 16 Days
measure: Renin
timeFrame: From -01 to 16 Days
measure: Creatinine clearance
timeFrame: From -01 to 16 Days
measure: Serum osteocalcin
timeFrame: From -01 to 16 Days
measure: Creatinine
timeFrame: From -01 to 16 Days
measure: Phosphate
timeFrame: From -01 to 16 Days
measure: Parathyroid hormone (PTH)
timeFrame: From -01 to 16 Days
Other outcomes:
Locations:
city: Köln
country: Germany
state: Nordrhein-Westfalen
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: