Effect of Riociguat on Bone Metabolism

Pharmacology, Clinical Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00855660
• Other study ID #: 13790
• Secondary ID: 2008-005569-70
• Status: Completed
• Phase: Phase 1
• First received: March 3, 2009
• Last updated: January 7, 2016
• Start date: March 2009
• Est. completion date: July 2010

Study information

• Verified date: January 2016
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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

Description:

Clinical pharmacology

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: July 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pharmacology, Clinical

Intervention

Drug:
• Riociguat (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.
• Placebo
Placebo administered as a single tablet, thrice daily, over 14 days.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

Germany, 

Outcome

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

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