Trial Outcomes & Findings for Single Dose Study in Patients With Chronic Obstructive Pulmonary Disease (COPD) Associated Pulmonary Hypertension. (NCT NCT00640315)
NCT ID: NCT00640315
Last Updated: 2016-12-28
Results Overview
PAPmean was reported during right heart catheterization
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
23 participants
Primary outcome timeframe
From baseline up to 4 hours after administration
Results posted on
2016-12-28
Participant Flow
Participant milestones
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
13
|
|
Overall Study
Participants Received Treatment
|
10
|
13
|
|
Overall Study
COMPLETED
|
10
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Single Dose Study in Patients With Chronic Obstructive Pulmonary Disease (COPD) Associated Pulmonary Hypertension.
Baseline characteristics by cohort
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=13 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
67.5 Years
STANDARD_DEVIATION 8.9 • n=5 Participants
|
69.2 Years
STANDARD_DEVIATION 5.7 • n=7 Participants
|
68.4 Years
STANDARD_DEVIATION 7.1 • n=5 Participants
|
|
Gender
Female
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Gender
Male
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population
PAPmean was reported during right heart catheterization
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Pulmonary Artery Pressure (PAPmean)
|
-3.60 mmHg
Standard Deviation 3.41
|
-4.83 mmHg
Standard Deviation 4.17
|
PRIMARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population (subjects with data available for this outcome measure)
PVR was calculated according to the formula PVR = 80\*(PAPmean - pulmonary capillary wedge pressure)/cardiac output
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=11 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance (PVR)
|
-58.32 (dyn*s*cm^-5)
Standard Deviation 50.46
|
-123.8 (dyn*s*cm^-5)
Standard Deviation 73.53
|
PRIMARY outcome
Timeframe: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dosePopulation: per-protocol population
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 1 (00d01h)
|
481.9 µg*h/L
Geometric Coefficient of Variation 65.3
|
1319 µg*h/L
Geometric Coefficient of Variation 56.8
|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 3 (02d01h)
|
605.5 µg*h/L
Geometric Coefficient of Variation 79.1
|
999.5 µg*h/L
Geometric Coefficient of Variation 61.6
|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 1 (00d01h)
|
NA µg*h/L
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
1019 µg*h/L
Geometric Coefficient of Variation 26.0
|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 3 (02d01h)
|
NA µg*h/L
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
NA µg*h/L
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
PRIMARY outcome
Timeframe: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dosePopulation: per-protocol population
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose (AUC/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 1 (00d01h)
|
481.9 10^3*h/L
Geometric Coefficient of Variation 65.3
|
527.4 10^3*h/L
Geometric Coefficient of Variation 56.8
|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose (AUC/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 3 (02d01h)
|
605.5 10^3*h/L
Geometric Coefficient of Variation 79.1
|
399.8 10^3*h/L
Geometric Coefficient of Variation 61.6
|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose (AUC/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 1 (00d01h)
|
NA 10^3*h/L
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
421.6 10^3*h/L
Geometric Coefficient of Variation 26.0
|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose (AUC/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 3 (02d01h)
|
NA 10^3*h/L
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
NA 10^3*h/L
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
PRIMARY outcome
Timeframe: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dosePopulation: per-protocol population
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose Per kg Body Weight (AUCnorm) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 1 (00d01h)
|
35.53 kg*h/L
Geometric Coefficient of Variation 62.6
|
38.85 kg*h/L
Geometric Coefficient of Variation 56.7
|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose Per kg Body Weight (AUCnorm) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 3 (02d01h)
|
44.86 kg*h/L
Geometric Coefficient of Variation 68.0
|
29.93 kg*h/L
Geometric Coefficient of Variation 65.7
|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose Per kg Body Weight (AUCnorm) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 1 (00d01h)
|
NA kg*h/L
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
31.03 kg*h/L
Geometric Coefficient of Variation 27.1
|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose Per kg Body Weight (AUCnorm) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 3 (02d01h)
|
NA kg*h/L
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
NA kg*h/L
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
PRIMARY outcome
Timeframe: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dosePopulation: per-protocol population
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 1 (00d01h)
|
42.96 µg/L
Geometric Coefficient of Variation 32.3
|
116.0 µg/L
Geometric Coefficient of Variation 36.0
|
|
Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 3 (02d01h)
|
35.30 µg/L
Geometric Coefficient of Variation 46.0
|
80.44 µg/L
Geometric Coefficient of Variation 27.3
|
|
Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 1 (00d01h)
|
10.44 µg/L
Geometric Coefficient of Variation 56.5
|
27.27 µg/L
Geometric Coefficient of Variation 34.9
|
|
Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 3 (02d01h)
|
9.869 µg/L
Geometric Coefficient of Variation 37.2
|
26.49 µg/L
Geometric Coefficient of Variation 26.5
|
PRIMARY outcome
Timeframe: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dosePopulation: per-protocol population
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 1 (00d01h)
|
42.96 10^3/L
Geometric Coefficient of Variation 32.3
|
46.42 10^3/L
Geometric Coefficient of Variation 36.0
|
|
Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 3 (02d01h)
|
35.30 10^3/L
Geometric Coefficient of Variation 46.0
|
32.18 10^3/L
Geometric Coefficient of Variation 27.3
|
|
Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 1 (00d01h)
|
10.80 10^3/L
Geometric Coefficient of Variation 56.5
|
11.28 10^3/L
Geometric Coefficient of Variation 34.9
|
|
Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 3 (02d01h)
|
10.21 10^3/L
Geometric Coefficient of Variation 37.2
|
10.96 10^3/L
Geometric Coefficient of Variation 26.5
|
PRIMARY outcome
Timeframe: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dosePopulation: per-protocol population
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 1 (00d01h)
|
3.185 kg/L
Geometric Coefficient of Variation 27.0
|
3.419 kg/L
Geometric Coefficient of Variation 30.9
|
|
Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 3 (02d01h)
|
2.617 kg/L
Geometric Coefficient of Variation 39.1
|
2.370 kg/L
Geometric Coefficient of Variation 31.4
|
|
Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 1 (00d01h)
|
0.800 kg/L
Geometric Coefficient of Variation 46.8
|
0.831 kg/L
Geometric Coefficient of Variation 31.7
|
|
Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 3 (02d01h)
|
0.757 kg/L
Geometric Coefficient of Variation 26.8
|
0.807 kg/L
Geometric Coefficient of Variation 27.5
|
SECONDARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population (subjects with data available for this outcome measure)
RAPmean was reported during right heart catheterization
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=11 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Right Atrial Pressure (RAPmean)
|
-2.00 mmHg
Standard Deviation 1.41
|
-0.64 mmHg
Standard Deviation 1.69
|
SECONDARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population (subjects with data available for this outcome measure)
PAPsyst was acquired during right heart catheterization
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Pulmonary Artery Pressure (PAPsyst)
|
-6.90 mmHg
Standard Deviation 4.86
|
-9.42 mmHg
Standard Deviation 6.73
|
SECONDARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population
PAPdiast was acquired during right heart catheterization
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Pulmonary Artery Pressure (PAPdiast)
|
-3.80 mmHg
Standard Deviation 4.73
|
-3.25 mmHg
Standard Deviation 2.83
|
SECONDARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population (subjects with data available for this outcome measure)
PCWP was acquired during right heart catheterization
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Capillary Wedge Pressure (PCWP)
|
-3.60 mmHg
Standard Deviation 3.57
|
-1.17 mmHg
Standard Deviation 3.38
|
SECONDARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population
HR was acquired during right heart catheterization
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Heart Rate (HR)
|
9.40 beats per minute
Standard Deviation 7.31
|
13.92 beats per minute
Standard Deviation 8.68
|
SECONDARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population
Systolic arterial blood pressure was acquired during right heart catheterization.
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Blood Pressure (SBP)
|
-26.30 mmHg
Standard Deviation 16.63
|
-22.17 mmHg
Standard Deviation 15.24
|
SECONDARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population
Diastolic arterial blood pressure was acquired during right heart catheterization.
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Blood Pressure (DBP)
|
-13.50 mmHg
Standard Deviation 6.84
|
-11.25 mmHg
Standard Deviation 9.50
|
SECONDARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population
MAP was acquired during right heart catheterization
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Arterial Pressure (MAP)
|
-17.10 mmHg
Standard Deviation 7.71
|
-13.92 mmHg
Standard Deviation 8.03
|
SECONDARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population (subjects with data available for this outcome measure)
CO was measured in triplicate by the thermodilution technique
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=11 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Output (CO)
|
0.66 L/min
Standard Deviation 0.48
|
1.61 L/min
Standard Deviation 1.49
|
SECONDARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population (subjects with data available for this outcome measure)
PVRI was calculated as PVRI = (80\*(PAPmean - PCWP)/CO)\*body surface area
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=11 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance Index (PVRI)
|
-108.6 dyn*s*cm^-5*m^2
Standard Deviation 93.46
|
-222.1 dyn*s*cm^-5*m^2
Standard Deviation 130.69
|
SECONDARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population (subjects with data available for this outcome measure)
SVR was calculated as SVR = 80\*(MAP-RAPmean)/CO
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=10 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance (SVR)
|
-440.0 dyn*s*cm^-5
Standard Deviation 205.78
|
-467.7 dyn*s*cm^-5
Standard Deviation 154.94
|
SECONDARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population (subjects with data available for this outcome measure)
SVRI was calculated as SVRI = (80\*(MAP - RAPmean)/CO)\*body surface area
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=10 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance Index (SVRI)
|
-836.4 dyn*s*cm^-5*m^2
Standard Deviation 385.92
|
-837.9 dyn*s*cm^-5*m^2
Standard Deviation 276.17
|
SECONDARY outcome
Timeframe: From baseline up to 4 hours after administrationPopulation: per-protocol population (subjects with data available for this outcome measure)
Cardiac index was calculated as cardiac index = CO / body surface area.
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=11 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Index
|
0.35 L/min/m^2
Standard Deviation 0.26
|
0.89 L/min/m^2
Standard Deviation 0.83
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Arterial blood gas analysis was performed by insertion of an indwelling arterial cannula. Percent change was calculated as "100%\*(value post dose - value at baseline)/ value at baseline".
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=9 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Oxygen Pressure (PaO2)
|
-12.64 Percentage
Standard Deviation 24.79
|
-12.99 Percentage
Standard Deviation 14.00
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Arterial blood gas analysis was performed by insertion of an indwelling arterial cannula. Percent change was calculated as "100%\*(value post dose - value at baseline)/ value at baseline".
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=9 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Pressure of Carbon Dioxide (PaCO2)
|
4.43 Percentage
Standard Deviation 20.93
|
4.04 Percentage
Standard Deviation 13.27
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Percent change was calculated as "100%\*(value post dose - value at baseline)/ value at baseline".
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=6 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Pressure (PvO2)
|
0.87 Percentage
Standard Deviation 8.57
|
12.07 Percentage
Standard Deviation 10.53
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Arterial blood gas analysis was performed by insertion of an indwelling arterial cannula. Percent change was calculated as "100%\*(value post dose - value at baseline)/ value at baseline".
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=9 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Oxygen Saturation (SaO2)
|
-2.23 Percentage
Standard Deviation 3.89
|
-2.89 Percentage
Standard Deviation 3.84
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Percent change was calculated as "100%\*(value post dose - value at baseline)/ value at baseline".
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=7 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Saturation (SvO2)
|
0.27 Percentage
Standard Deviation 6.58
|
6.76 Percentage
Standard Deviation 6.10
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=11 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Expiratory Volume in 1 Second (FEV1)
|
2.90 Percentage
Standard Deviation 3.32
|
3.81 Percentage
Standard Deviation 11.55
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=11 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FEV1
|
3.00 Percentage
Standard Deviation 3.38
|
4.35 Percentage
Standard Deviation 11.88
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=11 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Vital Capacity (FVC)
|
5.16 Percentage
Standard Deviation 16.08
|
8.62 Percentage
Standard Deviation 23.73
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=8 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=11 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FVC
|
0.41 Percentage
Standard Deviation 8.01
|
8.65 Percentage
Standard Deviation 23.77
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=11 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of FEV1/FVC
|
-0.69 Percentage
Standard Deviation 11.26
|
-1.29 Percentage
Standard Deviation 17.98
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=10 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Lung Capacity (TLC)
|
1.86 Percentage
Standard Deviation 10.53
|
2.14 Percentage
Standard Deviation 10.85
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
The percent of predicted TLC was provided by investigator at site.
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=10 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted TLC
|
1.91 Percentage
Standard Deviation 10.63
|
2.08 Percentage
Standard Deviation 10.92
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=10 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Residual Volume (RV)
|
0.80 Percentage
Standard Deviation 9.15
|
3.16 Percentage
Standard Deviation 22.39
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=10 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted RV
|
0.83 Percentage
Standard Deviation 9.09
|
3.21 Percentage
Standard Deviation 22.46
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=7 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=11 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 75% of Expiratory Vital Capacity (MEF75)
|
-0.92 Percentage
Standard Deviation 22.28
|
-1.09 Percentage
Standard Deviation 17.38
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=10 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 50% of Expiratory Vital Capacity (MEF50)
|
0.17 Percentage
Standard Deviation 18.29
|
5.59 Percentage
Standard Deviation 15.03
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=8 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=8 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 25% of Expiratory Vital Capacity (MEF25)
|
8.56 Percentage
Standard Deviation 29.57
|
-0.61 Percentage
Standard Deviation 40.44
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=9 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Airway Resistance (Raw)
|
-5.78 Percentage
Standard Deviation 24.03
|
-5.89 Percentage
Standard Deviation 34.27
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=11 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Vital Capacity (VC)
|
7.55 Percentage
Standard Deviation 22.35
|
10.09 Percentage
Standard Deviation 20.50
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=9 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=11 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted VC
|
7.60 Percentage
Standard Deviation 22.89
|
10.00 Percentage
Standard Deviation 20.45
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=7 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=5 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
|
15.67 Percentage
Standard Deviation 26.65
|
18.66 Percentage
Standard Deviation 17.39
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=7 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=4 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Lung Capacity at the Time When the DLCO is Measured (Alveolar Volume, VA)
|
-2.35 Percentage
Standard Deviation 6.90
|
1.72 Percentage
Standard Deviation 12.79
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=8 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=4 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Specific Diffusing Capacity
|
20.77 Percentage
Standard Deviation 27.36
|
18.61 Percentage
Standard Deviation 16.49
|
SECONDARY outcome
Timeframe: Baseline and 1 hour post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=5 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=2 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Ventilation (V)
|
-0.90 L/min
Standard Deviation 1.00
|
-0.10 L/min
Standard Deviation 0.20
|
SECONDARY outcome
Timeframe: Baseline and 1 hour post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=5 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=2 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Perfusion (Q)
|
0.30 L/min
Standard Deviation 0.50
|
-0.40 L/min
Standard Deviation 0.50
|
SECONDARY outcome
Timeframe: Baseline and 1 hour post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=5 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=1 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Dead Space Ventilation
|
3.20 Percentage of total ventilation
Standard Deviation 8.50
|
-42.50 Percentage of total ventilation
Standard Deviation NA
n=1
|
SECONDARY outcome
Timeframe: Baseline and 1 hour post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=4 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=1 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Low V/Q Perfusion
|
3.00 Percentage
Standard Deviation 13.40
|
-0.30 Percentage
Standard Deviation NA
n=1
|
SECONDARY outcome
Timeframe: Baseline and 1 hour post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=5 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=1 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Normal V/Q Perfusion
|
-9.80 Percentage
Standard Deviation 21.00
|
4.10 Percentage
Standard Deviation NA
n=1
|
SECONDARY outcome
Timeframe: Baseline and 1 hour post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=5 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=1 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hours Post Dose of Ventilation-perfusion Distribution Presented as Standard Deviation (SD) of Perfusion
|
0.00 L/MIN
Standard Deviation 0.10
|
-0.10 L/MIN
Standard Deviation NA
n=1
|
SECONDARY outcome
Timeframe: Baseline and 1 hour post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=5 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=1 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Ventilation-perfusion Distribution Presented as Standard Deviation (SD) of Ventilation
|
-0.10 L/MIN
Standard Deviation 0.40
|
-0.50 L/MIN
Standard Deviation NA
n=1
|
SECONDARY outcome
Timeframe: Baseline and 1 hour post dosePopulation: per-protocol population (subjects with data available for this outcome measure)
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=5 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=1 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Intrapulmonary Shunt Flow
|
-1.10 Percentage of total perfusion
Standard Deviation 1.70
|
-0.30 Percentage of total perfusion
Standard Deviation NA
n=1
|
SECONDARY outcome
Timeframe: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dosePopulation: per-protocol population
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 1 (00d01h)
|
1.75 hour
Interval 0.917 to 4.0
|
1.742 hour
Interval 1.0 to 7.75
|
|
Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 3 (02d01h)
|
2.033 hour
Interval 2.0 to 5.917
|
2.042 hour
Interval 1.867 to 24.83
|
|
Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 1 (00d01h)
|
11.97 hour
Interval 4.0 to 36.25
|
10.04 hour
Interval 3.0 to 24.33
|
|
Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 3 (02d01h)
|
9.017 hour
Interval 2.15 to 24.42
|
12.04 hour
Interval 2.0 to 24.03
|
SECONDARY outcome
Timeframe: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dosePopulation: per-protocol population
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 1 (00d01h)
|
8.422 hour
Geometric Coefficient of Variation 58.6
|
9.541 hour
Geometric Coefficient of Variation 50.7
|
|
Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 3 (02d01h)
|
12.18 hour
Geometric Coefficient of Variation 47.5
|
8.835 hour
Geometric Coefficient of Variation 50.8
|
|
Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 1 (00d01h)
|
NA hour
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
20.57 hour
Geometric Coefficient of Variation 46.4
|
|
Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 3 (02d01h)
|
NA hour
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
NA hour
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
SECONDARY outcome
Timeframe: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dosePopulation: per-protocol population
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 1 (00d01h)
|
12.92 hour
Geometric Coefficient of Variation 50.2
|
13.97 hour
Geometric Coefficient of Variation 46.5
|
|
Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 3 (02d01h)
|
18.88 hour
Geometric Coefficient of Variation 39.5
|
13.37 hour
Geometric Coefficient of Variation 46.5
|
|
Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 1 (00d01h)
|
NA hour
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
34.77 hour
Geometric Coefficient of Variation 41.1
|
|
Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 3 (02d01h)
|
NA hour
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
NA hour
Geometric Coefficient of Variation NA
Insufficient number of participants with data.
|
SECONDARY outcome
Timeframe: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dosePopulation: per-protocol population
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=12 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Area Under the Plasma Concentration Verse Time Curve From Zero to the Last Data Point (AUC0-tn) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 1 (00d01h)
|
426.3 µg*h/L
Geometric Coefficient of Variation 66.1
|
1196 µg*h/L
Geometric Coefficient of Variation 55.8
|
|
Area Under the Plasma Concentration Verse Time Curve From Zero to the Last Data Point (AUC0-tn) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Riociguat - Study day 3 (02d01h)
|
294.7 µg*h/L
Geometric Coefficient of Variation 81.6
|
750.3 µg*h/L
Geometric Coefficient of Variation 41.3
|
|
Area Under the Plasma Concentration Verse Time Curve From Zero to the Last Data Point (AUC0-tn) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 1 (00d01h)
|
200.1 µg*h/L
Geometric Coefficient of Variation 76.6
|
727.4 µg*h/L
Geometric Coefficient of Variation 20.1
|
|
Area Under the Plasma Concentration Verse Time Curve From Zero to the Last Data Point (AUC0-tn) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Metabolite M1 - Study day 3 (02d01h)
|
139.4 µg*h/L
Geometric Coefficient of Variation 98.8
|
490.6 µg*h/L
Geometric Coefficient of Variation 29.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and day 3Population: All subjects who received at least one dose of the trial medication were included in the safety evaluation.
PR duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=8 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=6 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Mean PR Duration (PRmean) - Change From Baseline to Day 3
|
0.64 msec
Standard Deviation 21.60
|
11.20 msec
Standard Deviation 27.57
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and day 3Population: All subjects who received at least one dose of the trial medication were included in the safety evaluation.
QRS duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=8 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=8 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Mean QRS Duration (QRSmean) - Change From Baseline to Day 3
|
-2.56 msec
Standard Deviation 5.79
|
0.68 msec
Standard Deviation 12.99
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and day 3Population: All subjects who received at least one dose of the trial medication were included in the safety evaluation.
QT duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=6 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=4 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Mean QT Duration (QTmean) - Change From Baseline to Day 3
|
-2.00 msec
Standard Deviation 22.03
|
-36.88 msec
Standard Deviation 15.48
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and day 3Population: All subjects who received at least one dose of the trial medication were included in the safety evaluation.
Bazett-corrected QTcB duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=6 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=4 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Mean QTcB Duration (Bazett's Correction Formula, QTcB) - Change From Baseline to Day 3
|
-1.45 msec
Standard Deviation 23.08
|
0.95 msec
Standard Deviation 13.49
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and day 3Population: All subjects who received at least one dose of the trial medication were included in the safety evaluation.
Fridericia-corrected QTcF duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Outcome measures
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=6 Participants
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=4 Participants
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Mean QTcF Duration (Fridericia's Correction Formula, QTcF) - Change From Baseline to Day 3
|
-1.58 msec
Standard Deviation 20.15
|
-12.73 msec
Standard Deviation 10.50
|
Adverse Events
Riociguat (Adempas, BAY63-2521) 1.0 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Riociguat (Adempas, BAY63-2521) 2.5 mg
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 participants at risk
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=13 participants at risk
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.00%
0/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
7.7%
1/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
|
Infections and infestations
Infective exacerbation of chronic obstructive airways disease
|
0.00%
0/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
7.7%
1/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
Other adverse events
| Measure |
Riociguat (Adempas, BAY63-2521) 1.0 mg
n=10 participants at risk
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
|
Riociguat (Adempas, BAY63-2521) 2.5 mg
n=13 participants at risk
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
7.7%
1/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
|
Cardiac disorders
Palpitations
|
0.00%
0/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
7.7%
1/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
|
Cardiac disorders
Ventricular extrasystoles
|
10.0%
1/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
0.00%
0/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
7.7%
1/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
|
Eye disorders
Visual impairment
|
0.00%
0/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
7.7%
1/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
7.7%
1/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
7.7%
1/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
|
Infections and infestations
Nasopharyngitis
|
10.0%
1/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
0.00%
0/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
|
Infections and infestations
Respiratory tract infection
|
10.0%
1/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
0.00%
0/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
|
Investigations
C-reactive protein increased
|
0.00%
0/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
7.7%
1/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
|
Nervous system disorders
Dizziness
|
10.0%
1/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
7.7%
1/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
7.7%
1/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/10 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
7.7%
1/13 • Adverse event data were collected after signing the informed consent until 30 days after end of study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Investigator may prepare the data derived from the Trial for publication. Such data will be submitted to the Sponsor for review at least 60 days prior to submission for publication. The Sponsor should respond within 50 days after receipt of the manuscript. The Investigator agrees that all reasonable comments made by the Sponsor in relation to a proposed publication will be incorporated. Confidential data provided by the Sponsor may not be published without written approval of the Sponsor.
- Publication restrictions are in place
Restriction type: OTHER