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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

Tracking Information
First Submitted Date  ICMJE March 3, 2009
First Posted Date  ICMJE March 4, 2009
Last Update Posted Date January 11, 2016
Study Start Date  ICMJE March 2009
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 30, 2015)
  • 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
  • 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)
  • AUC(0-7)ss [ Time Frame: Pre-dose and up to 7 hours post-dose on Day 13 ]
    AUC(0-7) at steady state
  • 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)
  • 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)
Original Primary Outcome Measures  ICMJE
 (submitted: March 3, 2009)
The primary objective of this study is to investigate the effect of multiple-dose riociguat (2.5 mg tid over 14 days) on bone resorption and formation markers [ Time Frame: At each study day from day -1 to day 16 ]
Change History Complete list of historical versions of study NCT00855660 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2016)
  • Number of participants with adverse events [ Time Frame: Approximately 12 weeks ]
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • %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)
  • 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
  • Serum CTX [ Time Frame: From -01 to 16 Days ]
    Marker of bone resorption
  • Serum N-terminal propeptide of type I collagen (PINP) [ Time Frame: From -01 to 16 Days ]
    Marker of bone formation
  • Serum bone-specific alkaline phosphatase (bAP) [ Time Frame: From -01 to 16 Days ]
    Marker of bone formation
  • Serum albumin, protein [ Time Frame: From -01 to 16 Days ]
    Determination of albumin, protein in serum
  • Cyclic guanosine monophosphate (cGMP) [ Time Frame: From -01 to 16 Days ]
    Determination of cGMP in plasma and urinary excretion (over 24 hours)
  • Calcium, sodium, potassium [ Time Frame: From -01 to 16 Days ]
    Determination of calcium, sodium, potassium in serum and urinary excretion (over 24 hours)
  • Urine volume [ Time Frame: From -01 to 16 Days ]
    Volume of urine excreted (over 24 hours)
  • Renin [ Time Frame: From -01 to 16 Days ]
    Determination of plasma renin level
  • Creatinine clearance [ Time Frame: From -01 to 16 Days ]
    For estimation of glomerular filtration rate
  • Serum osteocalcin [ Time Frame: From -01 to 16 Days ]
    Determination of osteocalcin in serum
  • Creatinine [ Time Frame: From -01 to 16 Days ]
    Determination of creatinine in serum and urinary excretion (over 24 hours)
  • Phosphate [ Time Frame: From -01 to 16 Days ]
    Determination of phosphate in serum only
  • Parathyroid hormone (PTH) [ Time Frame: From -01 to 16 Days ]
    Determination of PTH in serum only
Original Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2009)
  • Investigation of the pharmacokinetics of riociguat [ Time Frame: At each study day from day -1 to day 16 ]
  • Assessment of safety and tolerability [ Time Frame: At each study day from day -1 to day 16 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Riociguat on Bone Metabolism
Official Title  ICMJE 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
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Pharmacology, Clinical
Intervention  ICMJE
  • 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.
  • Drug: Placebo
    Placebo administered as a single tablet, thrice daily, over 14 days.
Study Arms  ICMJE
  • Active Comparator: Riociguat
    Subjects received multiple doses of riociguat (thrice a day) with concomitant administration of ranitidine (once daily) for 14 days
    Intervention: Drug: Riociguat (Adempas, BAY63-2521) immediate release tablet of 2.5 mg
  • Placebo Comparator: Placebo
    Subjects received placebo (thrice a day) with concomitant administration of ranitidine (once daily) for 14 days
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 11, 2015)
17
Original Estimated Enrollment  ICMJE
 (submitted: March 3, 2009)
16
Actual Study Completion Date  ICMJE July 2010
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00855660
Other Study ID Numbers  ICMJE 13790
2008-005569-70 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bayer Study Director Bayer
PRS Account Bayer
Verification Date January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP