A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With Pulmonary Arterial Hypertension (PAH) (PATENT-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00810693
First received: December 17, 2008
Last updated: January 24, 2014
Last verified: January 2014
Results First Received: November 5, 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 participants with symptomatic Pulmonary arterial hypertension (PAH) could participate in this study. Both treatment-naïve participants and participants pre-treated with an endothelin receptor antagonist or a non-intravenous prostacyclin analogue could be included.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
586 participants were enrolled in 124 study centers in 30 countries worldwide. 141 of the 586 enrolled participants were not randomized (adverse event [4], protocol violation [129], withdrawal by subject [8]). 445 of the 586 participants were randomized. 443 of the 445 randomized participants received study medication.

Reporting Groups
  Description
Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT 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 12 weeks
Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT Participants received Riociguat orally as a film-coated tablet up to 1.5mg three times daily (tid) (titration between 1.0 mg and 1.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks
Placebo Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks

Participant Flow for 2 periods

Period 1:   Treatment Period
    Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT     Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT     Placebo  
STARTED     254     64 [1]   127 [1]
Participants Received Treatment     254     63     126  
COMPLETED     237     57     111  
NOT COMPLETED     17     7     16  
Adverse Event                 8                 1                 7  
Death                 0                 1                 2  
Lack of Efficacy                 0                 0                 1  
Lost to Follow-up                 1                 0                 0  
Non-compliance                 1                 0                 0  
Protocol Violation                 1                 2                 2  
Withdrawal by Subject                 6                 2                 3  
Not treated                 0                 1                 1  
[1] 1 randomized but not treated

Period 2:   Follow-up Period (FUP)
    Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT     Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT     Placebo  
STARTED     23 [1]   7 [1]   16 [1]
COMPLETED     15     4     12  
NOT COMPLETED     8     3     4  
Adverse Event                 3                 1                 1  
Death                 2                 0                 1  
Lost to Follow-up                 1                 0                 2  
Protocol Violation                 0                 1                 0  
Withdrawal by Subject                 2                 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) up to 2.5 mg_IDT 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 12 weeks
Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT Participants received Riociguat orally as a film-coated tablet up to 1.5mg three times daily (tid) (titration between 1.0 mg and 1.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks
Placebo Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks
Total Total of all reporting groups

Baseline Measures
    Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT     Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT     Placebo     Total  
Number of Participants  
[units: participants]
  254     63     126     443  
Age  
[units: Years]
Mean ± Standard Deviation
  51.1  ± 16.6     48.8  ± 16.1     50.7  ± 16.5     50.6  ± 16.5  
Gender  
[units: Participants]
       
Female     203     49     98     350  
Male     51     14     28     93  
Race/Ethnicity, Customized  
[units: Participants]
       
White     161     33     78     272  
Black or African American     4     1     1     6  
Asian     79     22     38     139  
Mixed     1     0     1     2  
Not reported     9     7     8     24  
Prior PH therapy  
[units: Participants]
       
Therapy-Naive     123     32     66     221  
Pre-Treated     131     31     60     222  
pre-treated with endothelin receptor antagonist [1]
[units: Participants]
       
Yes     113     27     54     194  
No     141     36     72     249  
pre-treated with prostacyclin analogue [2]
[units: Participants]
       
Yes     20     4     7     31  
No     234     59     119     412  
PAH subtype [3]
[units: Participants]
       
Idiopathic PAH     149     39     84     272  
Familial PAH     7     1     1     9  
Connective tissue disease assoc. PAH     71     15     25     111  
Congenital heart disease (operated) assoc. PAH     15     8     12     35  
Portal Pulmonary hypertension     11     0     2     13  
Anorexigen or Amphtamin assoc: PAH     1     0     2     3  
BMI  
[units: kg/m^2]
Mean ± Standard Deviation
  25.91  ± 5.48     26.85  ± 5.35     26.26  ± 5.92     26.14  ± 5.59  
Baseline 6MWD [4]
[units: meters]
Mean ± Standard Deviation
  361.4  ± 67.7     363.2  ± 66.6     367.8  ± 74.6     363.5  ± 69.5  
WHO (World Health Organization) functional class [5]
[units: Participants]
       
I     5     5     4     14  
II     108     19     60     187  
III     140     39     58     237  
IV     1     0     3     4  
missing     0     0     1     1  
Pulmonary vascular resistance [6]
[units: dn*s*cm^-5]
Mean ± Standard Deviation
  790.96  ± 452.60     847.81  ± 548.17     834.06  ± 476.71     810.89  ± 473.45  
[1] Subjects pre-treated with an endothelin receptor antagonist.
[2] Subjects pre-treated with a prostacyclin analogue.
[3] Subtypes acc. to the Venice Clinical Classification of PH, Group 1 (idiopathic PAH, familial PAH, associated PAH due to [1] connective tissue disease, [2] congenital heart disease, [3] portal hypertension with liver cirrhosis, or [4] anorexigen or amphetamine use)
[4] 6-minute walking distance (6MWD) is a measure for the objective evaluation of a patient's functional exercise capacity.
[5] The WHO functional assessment of pulmonary arterial hypertension ranged from functional class I (participants with PH but without resulting limitation of physical activity) to class IV (participants with PH with inability to carry out any physical activity without symptoms. These participants manifest signs of right-heart failure.). Changes to a lower WHO functional class resemble improvement; changes to a higher functional class resemble deterioration of PAH.
[6] 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 12   [ Time Frame: Baseline and week 12 ]

2.  Secondary:   Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 12   [ Time Frame: Baseline and week 12 ]

3.  Secondary:   N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 12   [ Time Frame: Baseline and week 12 ]

4.  Secondary:   World Health Organization (WHO) Functional Class - Change From Baseline to Week 12   [ Time Frame: Baseline and week 12 ]

5.  Secondary:   Percentage of Participants With Clinical Worsening   [ Time Frame: At week 12 ]

6.  Secondary:   Borg CR 10 Scale - Change From Baseline to Week 12   [ Time Frame: Baseline and week 12 ]

7.  Secondary:   EQ-5D Utility Score - Change From Baseline to Week 12   [ Time Frame: Baseline and week 12 ]

8.  Secondary:   Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 12   [ Time Frame: Baseline and week 12 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  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.


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: NCT00810693     History of Changes
Other Study ID Numbers: 12934, 2008-003482-68
Study First Received: December 17, 2008
Results First Received: November 5, 2013
Last Updated: January 24, 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
Greece: Ministry of Health and Welfare
Ireland: Irisch Medicines Board
Israel: Ministry of Health
Italy: Ministry of Health
Japan: Ministry of Health and Welfare
Korea: Food and Drug Administration
Mexico: Ministry of Health
Netherlands: Medicines Evaluetion Board
New Zealand: Medicines and Medical Devices Safety Authority
Poland: Ministry of Health and Social Security - Drug Institute
Portugal: Ministry of Health
Russia: Ministry of Health
Singapore: Ministry of Health
Spain: Ministry of Health and Consumption
Sweden: Medical Products Agency
Switzerland: Federal Office of Public Health
Thailand: Ministry 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