Effect of Riociguat on Bone Metabolism

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00855660
First received: March 3, 2009
Last updated: January 7, 2016
Last verified: January 2016
  Purpose
Investigation of the effect of Riociguat, administered as 2.5 mg IR-tablets TID over 14 days, on bone metabolism.

Condition Intervention Phase
Pharmacology, Clinical
Drug: Riociguat (Adempas, BAY63-2521) immediate release tablet of 2.5 mg
Drug: Placebo
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Urinary excretion (over 24 hours) of C-terminal cross-linking telopeptides of type I collagen (CTX) [ Time Frame: From Day -01 to 16 ] [ Designated as safety issue: No ]
    Marker of bone resorption

  • AUC(0-7) [ Time Frame: Pre-dose and up to 7 hours post-dose on Day 0 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pre-dose and up to 7 hours post-dose on Day 13 ] [ Designated as safety issue: No ]
    AUC(0-7) at steady state

  • Cmax [ Time Frame: Pre-dose and up to 7 hours post-dose on Day 0 ] [ Designated as safety issue: No ]
    Maximum drug concentration in plasma after single dose administration for riociguat and its metabolite M-1 (BAY60-4552)

  • Cmax,ss [ Time Frame: Pre-dose and up to 7 hours post-dose on Day 13 ] [ Designated as safety issue: No ]
    Maximum drug concentration in plasma at steady state during a dosage interval for riociguat and its metabolite M-1 (BAY60-4552)


Secondary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: Approximately 12 weeks ] [ Designated as safety issue: Yes ]
  • Ctrough [ Time Frame: On Days 03 and 08 ] [ Designated as safety issue: No ]
    Drug concentration in plasma at expected time of minimum (trough) concentration for riociguat and its metabolite M-1 (BAY60-4552)

  • AUC(0-7)norm [ Time Frame: Pre-dose and up to 7 hours post-dose on Day 0 ] [ Designated as safety issue: No ]
    AUC(0-7) divided by dose per kg body weight for riociguat and its metabolite M-1 (BAY60-4552)

  • AUC(0-7)ss,norm [ Time Frame: Pre-dose and up to 7 hours post-dose on Day 13 ] [ Designated as safety issue: No ]
    AUC(0-7)ss divided by dose per kg body weight for riociguat and its metabolite M-1 (BAY60-4552)

  • Cmax,norm [ Time Frame: Pre-dose and up to 7 hours post-dose on Day 0 ] [ Designated as safety issue: No ]
    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)

  • Cmax,ss,norm [ Time Frame: Pre-dose and up to 7 hours post-dose on Day 13 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pre-dose and up to 7 hours post-dose on Day 0 ] [ Designated as safety issue: No ]
    Time to reach maximum drug concentration in plasma after single (first) dose for riociguat and its metabolite M-1 (BAY60-4552)

  • tmax,ss [ Time Frame: Pre-dose and up to 7 hours post-dose on Day 13 ] [ Designated as safety issue: No ]
    tmax at steady state for riociguat and its metabolite M-1 (BAY60-4552)

  • Aeur(0-7) [ Time Frame: Pre-dose and up to 7 hours post-dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Pre-dose and up to 7 hours post-dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    Marker of bone resorption

  • Serum CTX [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    Marker of bone resorption

  • Serum N-terminal propeptide of type I collagen (PINP) [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    Marker of bone formation

  • Serum bone-specific alkaline phosphatase (bAP) [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    Marker of bone formation

  • Serum albumin, protein [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    Determination of albumin, protein in serum

  • Cyclic guanosine monophosphate (cGMP) [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    Determination of cGMP in plasma and urinary excretion (over 24 hours)

  • Calcium, sodium, potassium [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    Determination of calcium, sodium, potassium in serum and urinary excretion (over 24 hours)

  • Urine volume [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    Volume of urine excreted (over 24 hours)

  • Renin [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    Determination of plasma renin level

  • Creatinine clearance [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    For estimation of glomerular filtration rate

  • Serum osteocalcin [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    Determination of osteocalcin in serum

  • Creatinine [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    Determination of creatinine in serum and urinary excretion (over 24 hours)

  • Phosphate [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    Determination of phosphate in serum only

  • Parathyroid hormone (PTH) [ Time Frame: From -01 to 16 Days ] [ Designated as safety issue: No ]
    Determination of PTH in serum only


Enrollment: 17
Study Start Date: March 2009
Study Completion Date: July 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Riociguat
Subjects received multiple doses of riociguat (thrice a day) with concomitant administration of ranitidine (once daily) for 14 days
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 Comparator: Placebo
Subjects received placebo (thrice a day) with concomitant administration of ranitidine (once daily) for 14 days
Drug: Placebo
Placebo administered as a single tablet, thrice daily, over 14 days.

Detailed Description:
Clinical pharmacology
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00855660

Locations
Germany
Köln, Nordrhein-Westfalen, Germany, 51147
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00855660     History of Changes
Other Study ID Numbers: 13790  2008-005569-70 
Study First Received: March 3, 2009
Last Updated: January 7, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Bayer:
Bone Metabolism

ClinicalTrials.gov processed this record on May 26, 2016