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Effect of Riociguat on Bone Metabolism

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ClinicalTrials.gov Identifier: NCT00855660
Recruitment Status : Completed
First Posted : March 4, 2009
Last Update Posted : January 11, 2016
Sponsor:
Information provided by (Responsible Party):
Bayer

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

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

Detailed Description:
Clinical pharmacology

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, 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
Study Start Date : March 2009
Actual Primary Completion Date : December 2009
Actual Study Completion Date : July 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Riociguat
U.S. FDA Resources

Arm Intervention/treatment
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.



Primary Outcome Measures :
  1. Urinary excretion (over 24 hours) of C-terminal cross-linking telopeptides of type I collagen (CTX) [ Time Frame: From Day -01 to 16 ]
    Marker of bone resorption

  2. AUC(0-7) [ Time Frame: 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)

  3. AUC(0-7)ss [ Time Frame: Pre-dose and up to 7 hours post-dose on Day 13 ]
    AUC(0-7) at steady state

  4. Cmax [ Time Frame: 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)

  5. Cmax,ss [ Time Frame: 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 Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: Approximately 12 weeks ]
  2. Ctrough [ Time Frame: 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)

  3. AUC(0-7)norm [ Time Frame: 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)

  4. AUC(0-7)ss,norm [ Time Frame: 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)

  5. Cmax,norm [ Time Frame: 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)

  6. Cmax,ss,norm [ Time Frame: 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)

  7. tmax [ Time Frame: 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)

  8. tmax,ss [ Time Frame: 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)

  9. Aeur(0-7) [ Time Frame: 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)

  10. %Aeur(0-7) [ Time Frame: 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)

  11. Urinary excretion (over 24 hours) of N-terminal cross-linking telopeptides of type I collagen (NTX) [ Time Frame: From -01 to 16 Days ]
    Marker of bone resorption

  12. Serum CTX [ Time Frame: From -01 to 16 Days ]
    Marker of bone resorption

  13. Serum N-terminal propeptide of type I collagen (PINP) [ Time Frame: From -01 to 16 Days ]
    Marker of bone formation

  14. Serum bone-specific alkaline phosphatase (bAP) [ Time Frame: From -01 to 16 Days ]
    Marker of bone formation

  15. Serum albumin, protein [ Time Frame: From -01 to 16 Days ]
    Determination of albumin, protein in serum

  16. Cyclic guanosine monophosphate (cGMP) [ Time Frame: From -01 to 16 Days ]
    Determination of cGMP in plasma and urinary excretion (over 24 hours)

  17. Calcium, sodium, potassium [ Time Frame: From -01 to 16 Days ]
    Determination of calcium, sodium, potassium in serum and urinary excretion (over 24 hours)

  18. Urine volume [ Time Frame: From -01 to 16 Days ]
    Volume of urine excreted (over 24 hours)

  19. Renin [ Time Frame: From -01 to 16 Days ]
    Determination of plasma renin level

  20. Creatinine clearance [ Time Frame: From -01 to 16 Days ]
    For estimation of glomerular filtration rate

  21. Serum osteocalcin [ Time Frame: From -01 to 16 Days ]
    Determination of osteocalcin in serum

  22. Creatinine [ Time Frame: From -01 to 16 Days ]
    Determination of creatinine in serum and urinary excretion (over 24 hours)

  23. Phosphate [ Time Frame: From -01 to 16 Days ]
    Determination of phosphate in serum only

  24. Parathyroid hormone (PTH) [ Time Frame: From -01 to 16 Days ]
    Determination of PTH in serum only



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00855660


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