A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With CTEPH. (CHEST-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00855465
First received: December 15, 2008
Last updated: January 25, 2014
Last verified: January 2014
Results First Received: November 4, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Pulmonary Hypertension
Interventions: Drug: Riociguat (Adempas, BAY63-2521)
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Only subjects with symptomatic chronic thromboembolic pulmonary hypertension (CTEPH) could participate in this study. CTEPH was defined either as inoperable or as persisting or recurrent PH after pulmonary endarterectomy.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
446 subjects were screened in 89 study centers in 26 countries worldwide. 184 of the 446 screened subjects were not randomized (adverse event [1], death [4], protocol violation [164], withdrawal by subject [15]). 262 of the 446 subjects were randomized. 261 of the 262 randomized subjects received study medication.

Reporting Groups
  Description
Riociguat (Adempas, BAY63-2521)_individual Dose Titration Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 16 weeks
Placebo Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks

Participant Flow for 2 periods

Period 1:   Treatment Period
    Riociguat (Adempas, BAY63-2521)_individual Dose Titration     Placebo  
STARTED     174     88  
Participants Received Treatment     173 [1]   88  
COMPLETED     160     83  
NOT COMPLETED     14     5  
Adverse Event                 4                 2  
Death                 2                 2  
Lack of Efficacy                 2                 1  
Non-compliance                 1                 0  
Protocol Violation                 2                 0  
Withdrawal by Subject                 2                 0  
Not treated                 1                 0  
[1] 1 subject randomized but not treated

Period 2:   Follow-up Period (FUP)
    Riociguat (Adempas, BAY63-2521)_individual Dose Titration     Placebo  
STARTED     17 [1]   4 [1]
COMPLETED     9     2  
NOT COMPLETED     8     2  
Adverse Event                 0                 1  
Death                 0                 1  
Lost to Follow-up                 3                 0  
Withdrawal by Subject                 4                 0  
Missing                 1                 0  
[1] Started FUP only if prematurely withdrawn from trt period or if not entering LTE study.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Riociguat (Adempas, BAY63-2521)_individual Dose Titration Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 16 weeks
Placebo Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Total Total of all reporting groups

Baseline Measures
    Riociguat (Adempas, BAY63-2521)_individual Dose Titration     Placebo     Total  
Number of Participants  
[units: participants]
  173     88     261  
Age  
[units: Years]
Mean ± Standard Deviation
  59.3  ± 13.9     59.2  ± 12.7     59.3  ± 13.5  
Gender  
[units: Participants]
     
Female     118     54     172  
Male     55     34     89  
Race/Ethnicity, Customized  
[units: Participants]
     
White     120     65     185  
Black or African American     7     1     8  
Asian     37     20     57  
Mixed     1     0     1  
Not reported     8     2     10  
Operability [1]
[units: Participants]
     
Inoperable CTEPH     121     68     189  
Postoperative CTEPH     52     20     72  
Body Mass Index  
[units: kg/m^2]
Mean ± Standard Deviation
  27.13  ± 5.75     27.73  ± 5.30     27.33  ± 5.60  
6-minute walking distance [2]
[units: Meters]
Mean ± Standard Deviation
  342.3  ± 81.9     356.0  ± 74.7     346.9  ± 79.7  
WHO (World Health Organization) functional class [3]
[units: Participants]
     
missing     0     1     1  
I     3     0     3  
II     55     25     80  
III     107     60     167  
IV     8     2     10  
Pulmonary vascular resistance [4]
[units: dyn*s*cm^-5]
Mean ± Standard Deviation
  790.68  ± 431.57     779.32  ± 400.94     786.68  ± 420.21  
[1] CTEPH defined as inoperable or as persisting/recurrent PH after pulmonary endarterectomy (PEA).
[2] 6-minute walking distance (6MWD) is a measure for the objective evaluation of a participant's functional exercise capacity.
[3] The WHO functional assessment of pulmonary arterial hypertension ranged from functional class I (Patients with PH but without resulting limitation of physical activity) to class IV (Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure.). Changes to a lower WHO functional class resemble improvement; changes to a higher functional class resemble deterioration of pulmonary arterial hypertension (PAH).
[4] The pulmonary vascular resistance (PVR) is a calculated hemodynamic parameter. PVR is derived from the directly measured parameters mean pulmonary arterial pressure (PAPmean) and pulmonary capillary wedge pressure (PCWP), divided by the cardiac output (CO). PVR and PAPmean are acquired during a right heart catheterization. CO is a calculated hemodynamic parameter, too. Formula: PVR = 80*(PAPmean - PCWP)/CO



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

2.  Secondary:   Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

3.  Secondary:   N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

4.  Secondary:   World Health Organization (WHO) Functional Class - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

5.  Secondary:   Percentage of Participants With Clinical Worsening   [ Time Frame: At week 16 ]

6.  Secondary:   Borg CR 10 Scale - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

7.  Secondary:   EQ-5D Utility Score - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

8.  Secondary:   Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

9.  Other Pre-specified:   All Caused Mortality   [ Time Frame: At visit 6 (week 16) ]

10.  Other Pre-specified:   Mean Pulmonary Artery Pressure (PAPmean) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

11.  Other Pre-specified:   Cardiac Index (CI) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

12.  Other Pre-specified:   Systolic Blood Pressure (SBP) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

13.  Other Pre-specified:   Diastolic Blood Pressure (DBP) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

14.  Other Pre-specified:   Heart Rate (HR) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

15.  Other Pre-specified:   Alanine Aminotransferase (ALT) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

16.  Other Pre-specified:   Aspartate Aminotransferase (AST) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

17.  Other Pre-specified:   Alkaline Phosphatase (AP) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

18.  Other Pre-specified:   Bilirubin - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

19.  Other Pre-specified:   Creatinine - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

20.  Other Pre-specified:   Creatinine Clearance - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

21.  Other Pre-specified:   Creatine Kinase (CK) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

22.  Other Pre-specified:   Erythrocytes (RBC) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

23.  Other Pre-specified:   Leukocytes (WBC) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

24.  Other Pre-specified:   Lymphocytes - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

25.  Other Pre-specified:   Neutrophils - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

26.  Other Pre-specified:   Hemoglobin - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

27.  Other Pre-specified:   Hematocrit - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

28.  Other Pre-specified:   Potassium - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

29.  Other Pre-specified:   Urate - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

30.  Other Pre-specified:   Urea (BUN) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

31.  Other Pre-specified:   Cystatin C - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

32.  Other Pre-specified:   Triacylglycerol Lipase - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

33.  Other Pre-specified:   Arterial Partial Pressure of Carbon Dioxide (PaCO2) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

34.  Other Pre-specified:   Arterial Partial Oxygen Pressure (PaO2) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

35.  Other Pre-specified:   Oxygen Saturation (SaO2) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

36.  Other Pre-specified:   Mean PR Duration (PRmean) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

37.  Other Pre-specified:   Mean QRS Duration (QRSmean) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

38.  Other Pre-specified:   Mean QT Duration (QTmean) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

39.  Other Pre-specified:   Mean QTcB Duration (Bazett's Correction Formula, QTcB) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

40.  Other Pre-specified:   Mean QTcF Duration (Fridericia's Correction Formula, QTcF) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

41.  Other Pre-specified:   Mean RR Duration (RRmean) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]

42.  Other Pre-specified:   Mean Ventricular Rate (VRmean) - Change From Baseline to Week 16   [ Time Frame: Baseline and week 16 ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: Bayer
e-mail: clinical-trials-contact@bayerhealthcare.com


Publications of Results:

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00855465     History of Changes
Other Study ID Numbers: 11348, 2007-000072-16
Study First Received: December 15, 2008
Results First Received: November 4, 2013
Last Updated: January 25, 2014
Health Authority: Argentina: National Administration of Drugs, Foods and Medical Technology
Australia: Department of Health
Austria: Ministry of Labor, Health and Social Affairs
Belgium: Ministry of Social Affairs, Public Health and the Environment
Brazil: Ministry of Health
Canada: Health Protection Branch
China: Ministry of Health- State Food and Drug Administration
Czech Republic: Ministry of Health
Denmark: Danish Medicines Agency
France: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Israel: Ministry of Health
Italy: Ministry of Health
Japan: Ministry of Health and Welfare
Korea, Republic of: Food and Drug Administration
Mexico: Ministry of Health
Netherlands: Medicines Evaluation Board
Poland: Ministry of Health and Social Security- Drug Institute
Portugal: Ministry of Health
Russia: Ministry of Health
Slovakia: State Institute for Drug Control
Spain: Ministry of Health and Consumption
Switzerland: Federal Office of Public Health
Taiwan: Department of Health
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration