Study Completed

Pharmacology, clinical

Bayer Identifier:

13790

ClinicalTrials.gov Identifier:

NCT00855660

EudraCT Number:

2008-005569-70

EU CT Number:

Not Available

Effect of Riociguat on bone metabolism

Trial purpose

Investigation of the effect of Riociguat, administered as 2.5 mg IR-tablets TID over 14 days, on bone metabolism.

Key Participants Requirements

Sex

Male

Age

18 - 45 Years

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

Trial summary

Enrollment Goal

Trial Dates

March 2009 - July 2010

Phase

Phase 1

Could I Receive a placebo

Yes

Products

Adempas (Riociguat, BAY63-2521)

Accepts Healthy Volunteer

Yes

Where to participate

Status	Institution	Location
Completed	Deutsches Zentrum für Luft- und Raumfahrt e. V. (DLR)	Köln, 51147, Germany

Primary Outcome

Urinary excretion (over 24 hours) of C-terminal cross-linking telopeptides of type I collagen (CTX)
Marker of bone resorption
Time Frame:
From Day -01 to 16
Safety Issue:
No
AUC(0-7)
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)
Time Frame:
Pre-dose and up to 7 hours post-dose on Day 0
Safety Issue:
No
AUC(0-7)ss
AUC(0-7) at steady state
Time Frame:
Pre-dose and up to 7 hours post-dose on Day 13
Safety Issue:
No
Cmax
Maximum drug concentration in plasma after single dose administration for riociguat and its metabolite M-1 (BAY60-4552)
Time Frame:
Pre-dose and up to 7 hours post-dose on Day 0
Safety Issue:
No
Cmax,ss
Maximum drug concentration in plasma at steady state during a dosage interval for riociguat and its metabolite M-1 (BAY60-4552)
Time Frame:
Pre-dose and up to 7 hours post-dose on Day 13
Safety Issue:
No

Secondary Outcome

Number of participants with adverse events
Time Frame:
Approximately 12 weeks
Safety Issue:
yes
Ctrough
Drug concentration in plasma at expected time of minimum (trough) concentration for riociguat and its metabolite M-1 (BAY60-4552)
Time Frame:
On Days 03 and 08
Safety Issue:
No
AUC(0-7)norm
AUC(0-7) divided by dose per kg body weight for riociguat and its metabolite M-1 (BAY60-4552)
Time Frame:
Pre-dose and up to 7 hours post-dose on Day 0
Safety Issue:
No
AUC(0-7)ss,norm
AUC(0-7)ss divided by dose per kg body weight for riociguat and its metabolite M-1 (BAY60-4552)
Time Frame:
Pre-dose and up to 7 hours post-dose on Day 13
Safety Issue:
No
Cmax,norm
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)
Time Frame:
Pre-dose and up to 7 hours post-dose on Day 0
Safety Issue:
No
Cmax,ss,norm
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)
Time Frame:
Pre-dose and up to 7 hours post-dose on Day 13
Safety Issue:
No
tmax
Time to reach maximum drug concentration in plasma after single (first) dose for riociguat and its metabolite M-1 (BAY60-4552)
Time Frame:
Pre-dose and up to 7 hours post-dose on Day 0
Safety Issue:
No
tmax,ss
tmax at steady state for riociguat and its metabolite M-1 (BAY60-4552)
Time Frame:
Pre-dose and up to 7 hours post-dose on Day 13
Safety Issue:
No
Aeur(0-7)
Amount of drug excreted via urine from zero to 7 hours after administration for riociguat and its metabolite M-1 (BAY60-4552)
Time Frame:
Pre-dose and up to 7 hours post-dose
Safety Issue:
No
%Aeur(0-7)
Aeur(0-7) expressed as percent of dose administered for riociguat and its metabolite M-1 (BAY60-4552)
Time Frame:
Pre-dose and up to 7 hours post-dose
Safety Issue:
No
Urinary excretion (over 24 hours) of N-terminal cross-linking telopeptides of type I collagen (NTX)
Marker of bone resorption
Time Frame:
From -01 to 16 Days
Safety Issue:
No
Serum CTX
Marker of bone resorption
Time Frame:
From -01 to 16 Days
Safety Issue:
No
Serum N-terminal propeptide of type I collagen (PINP)
Marker of bone formation
Time Frame:
From -01 to 16 Days
Safety Issue:
No
Serum bone-specific alkaline phosphatase (bAP)
Marker of bone formation
Time Frame:
From -01 to 16 Days
Safety Issue:
No
Serum albumin, protein
Determination of albumin, protein in serum
Time Frame:
From -01 to 16 Days
Safety Issue:
No
Cyclic guanosine monophosphate (cGMP)
Determination of cGMP in plasma and urinary excretion (over 24 hours)
Time Frame:
From -01 to 16 Days
Safety Issue:
No
Calcium, sodium, potassium
Determination of calcium, sodium, potassium in serum and urinary excretion (over 24 hours)
Time Frame:
From -01 to 16 Days
Safety Issue:
No
Urine volume
Volume of urine excreted (over 24 hours)
Time Frame:
From -01 to 16 Days
Safety Issue:
No
Renin
Determination of plasma renin level
Time Frame:
From -01 to 16 Days
Safety Issue:
No
Creatinine clearance
For estimation of glomerular filtration rate
Time Frame:
From -01 to 16 Days
Safety Issue:
No
Serum osteocalcin
Determination of osteocalcin in serum
Time Frame:
From -01 to 16 Days
Safety Issue:
No
Creatinine
Determination of creatinine in serum and urinary excretion (over 24 hours)
Time Frame:
From -01 to 16 Days
Safety Issue:
No
Phosphate
Determination of phosphate in serum only
Time Frame:
From -01 to 16 Days
Safety Issue:
No
Parathyroid hormone (PTH)
Determination of PTH in serum only
Time Frame:
From -01 to 16 Days
Safety Issue:
No

Trial design

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

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Treatment

Allocation

Randomized

Blinding

Double Blind

Assignment

Crossover Assignment

Trial Arms

Additional Information

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