Evaluation of the Pharmacodynamic Effect of the Combination of Sildenafil and Riociguat on Blood Pressure and Other Safety Parameters.

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01179334
• Date of registration: 10/08/2010
• Prospective Registration: No
• Primary sponsor: Bayer
• Public title: Evaluation of the Pharmacodynamic Effect of the Combination of Sildenafil and Riociguat on Blood Pressure and Other Safety Parameters. PATENT PLUS
• Scientific title: An Interaction Study to Evaluate Changes in Blood Pressure Following 1, 1.5, 2, and 2.5 mg Riociguat Tid (Dose Titration) Compared to Placebo Treatment on the Background of Stable Sildenafil Pretreatment in Subjects With Symptomatic Pulmonary Arterial Hypertension
• Date of first enrolment: August 2010
• Target sample size: 18
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01179334
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

Austria, Czech Republic, Germany, Italy, New Zealand, Poland, Spain, United Kingdom, United States

Contacts

• Name: Bayer Study Director
• Affiliation: Bayer

Key inclusion & exclusion criteria

Inclusion Criteria:

- 18 to 75 years of age at Visit 1

- Male and female subjects with symptomatic PAH (Group I Dana Point Updated Clinical
Classification 2008), a 6-min walking distance (6MWD) of more than 150 m, a pulmonary
vascular resistance (PVR) >300 dyn*s*cm-5, and a mean pulmonary artery pressure
(PAPmean) = 25 mmHg

- For Study Part 1: subjects on stable pretreatment with sildenafil at a dose of 20 mg
tid

- Unspecific treatments which may also be used for the treatment of PAH such as oral
anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen
supplementation are permitted. However, treatment with anticoagulants (if indicated)
must have been started at least 30 days before Visit 1 and treatment with diuretics
needs to be stable for at least 30 days before Visit 1

- Subjects with supplemental long-term oxygen therapy may be included, if the amount of
supplemental oxygen and the delivery method was stable on average for at least 90 days
before Visit 1

- SBP >/=95 mmHg and heart rate (HR) after intake of sildenafil (measured at Visits 0 and 1)

- Women without child-bearing potential

- Subjects who are able to understand and follow instructions and who are able to
participate in the study for the entire period

- Subjects must have given their written informed consent to participate in the study
after having received adequate previous information and prior to any study-specific
procedures

Exclusion Criteria:

- Subject's participating in another clinical trial or who have done so within 30 days
before Visit 1

- Previous assignment to treatment during this study

- Pregnant women

- Subjects with a medical disorder, condition, or history of such that would impair the
subject's ability to participate or complete this study in the opinion of the
investigator

- Subjects with substance abuse (eg alcohol or drug abuse) within the previous 180 days
before Visit 1

- Subjects with underlying medical disorders with an anticipated life expectancy below 2
years (eg active cancer disease with localized and/or metastasized tumor mass)

- Subjects with a history of severe allergies or multiple drug allergies

- Subjects with hypersensitivity to the investigational drug or any of the excipients

- Subjects unable to perform a valid 6MWD test, eg subjects with a severe peripheral
artery occlusive disease

- Subjects with a relative difference (ie absolute difference/mean) of more than 15%
between the eligibility- and the baseline 6MWD test

- All types of pulmonary hypertension except subtypes of Updated Clinical Classification
of pulmonary hypertension (PH) (Dana Point 2008) Group I specified in the inclusion
criteria

- Moderate to severe obstructive lung disease (forced expiratory volume <60% predicted).
The predicted forced expiratory volume in 1 second (FEV1) is a calculated value

- Severe restrictive lung disease (total lung capacity <70% predicted). The predicted
total lung capacity (TLC) is a calculated value

- Severe congenital abnormalities of the lungs, thorax, and diaphragm

- Oxygen saturation (SaO2) <88% despite supplemental oxygen therapy

- Arterial partial oxygen pressure (PaO2) <55 mmHg despite supplemental oxygen therapy

- Arterial partial pressure of carbon dioxide (PaCO2) >45 mmHg

- Uncontrolled arterial hypertension (SBP >180 mmHg and /or diastolic blood pressure
>110 mmHg

- Atrial fibrillation within the last 90 days before Visit 1

- Pulmonary venous hypertension with pulmonary capillary wedge pressure 15 mmHg

- Hypertrophic obstructive cardiomyopathy

- Severe proven or suspected coronary artery disease

- Clinical evidence of symptomatic atherosclerotic disease

- Congenital or acquired valvular or myocardial disease if clinically significant apart
from tricuspid valvular insufficiency due to pulmonary hypertension

- Clinical relevant hepatic dysfunction indicated by:

- Bilirubin >2 times upper limit normal (ULN)

- and/or ALT (alanine aminotransferase) or AST (aspartate aminotransferase) >3
times ULN

- and/or signs of severe hepatic insufficiency (eg impaired albumin synthesis with
an albumin <32 g/L, hepatic encephalopathy > grade 1

- Renal insufficiency (glomerular filtration rate <30 mL/min, eg calculated based on the
Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formulas



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Hypertension

Intervention(s)

Drug: Placebo

Drug: Riociguat (Adempas, BAY63-2521)

Drug: Sildenafil

Primary Outcome(s)

Maximum Change From Baseline in Supine Systolic Blood Pressure (SBP) Within 4 Hours Post-dose at Visit 6 (Week 12) [Time Frame: Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)]

Secondary Outcome(s)

Maximum Change From Baseline in Standing Systolic Blood Pressure (SBP) Within 4 Hours Post-dose at Visit 6 (Week 12) [Time Frame: Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)]

Maximum Change From Baseline in Supine Heart Rate (HR) Within 4 Hours Post-dose at Visit 6 (Week 12) [Time Frame: Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)]

Area Under Effect Curve (AUEC) of Standing HR Within 4 Hours Post-dose at Visit 6 (Week 12) [Time Frame: Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)]

Maximum Change From Baseline in Supine Diastolic Blood Pressure (DBP) Within 4 Hours Post-dose at Visit 6 (Week 12) [Time Frame: Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)]

Maximum Change From Baseline in Standing Heart Rate (HR) Within 4 Hours Post-dose at Visit 6 (Week 12) [Time Frame: Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)]

Area Under Effect Curve (AUEC) of Standing DBP Within 4 Hours Post-dose at Visit 6 (Week 12) [Time Frame: Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)]

Area Under Effect Curve (AUEC) of Supine SBP Within 4 Hours Post-dose at Visit 6 (Week 12) [Time Frame: Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)]

Maximum Change From Baseline in Standing Diastolic Blood Pressure (DBP) Within 4 Hours Post-dose at Visit 6 (Week 12) [Time Frame: Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)]

Area Under Effect Curve (AUEC) of Standing SBP Within 4 Hours Post-dose at Visit 6 (Week 12) [Time Frame: Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)]

Area Under Effect Curve (AUEC) of Supine DBP Within 4 Hours Post-dose at Visit 6 (Week 12) [Time Frame: Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)]

Area Under Effect Curve (AUEC) of Supine HR Within 4 Hours Post-dose at Visit 6 (Week 12) [Time Frame: Pre-dose (baseline) and within 4 hours post-dose at visit 6 (week 12)]

Secondary ID(s)

2010-018863-40

15096

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 25/12/2013
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01179334