Trial Outcomes & Findings for Efficacy Study of Riociguat and Its Effects on Exercise Performance and Pulmonary Artery Pressure at High Altitude (NCT NCT02024386)
NCT ID: NCT02024386
Last Updated: 2017-04-12
Results Overview
Subject pulmonary artery pressures will be continuously monitored during the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Exercise level will be increased every 3 minutes until test termination criteria are achieved. Measurements will be obtained at rest, every 3 minutes during the exercise test (referred to as a stage below) and at 5 minutes post exercise. Results will be reported as a 30 second average. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
28 participants
Primary outcome timeframe
At rest, every 3 minutes during the exercise test and 5 minutes after each exercise test
Results posted on
2017-04-12
Participant Flow
Six additional subjects were consented but not enrolled. Two subjects failed the screen due to a VO2 max less than the inclusion criteria. Two subjects were withdrawn when the Swan-Ganz catheter could not be placed. One subject was unable to schedule an experimental date and one subject did not return for screening.
Participant milestones
| Measure |
Riociguat 0.5 mg
Riociguat 0.5 mg tablets, one-time oral dose of 0.5
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Riociguat 1.0 mg
Riociguat 0.5 mg tablets, one-time oral dose of 1.0 mg
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Control Arm
No drug
After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude.
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
11
|
5
|
|
Overall Study
COMPLETED
|
6
|
11
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy Study of Riociguat and Its Effects on Exercise Performance and Pulmonary Artery Pressure at High Altitude
Baseline characteristics by cohort
| Measure |
Riociguat 0.5 mg
n=6 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 0.5
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Riociguat 1.0 mg
n=11 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 1.0 mg
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Control Arm
n=5 Participants
No drug
After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude.
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
31.5 years
STANDARD_DEVIATION 7.2 • n=5 Participants
|
24.3 years
STANDARD_DEVIATION 4.4 • n=7 Participants
|
24.8 years
STANDARD_DEVIATION 5.2 • n=5 Participants
|
26.4 years
STANDARD_DEVIATION 6.1 • n=4 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
11 participants
n=7 Participants
|
5 participants
n=5 Participants
|
22 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: At rest, every 3 minutes during the exercise test and 5 minutes after each exercise testPopulation: Not all subjects performed the same number of exercise stages to achieve VO2max.
Subject pulmonary artery pressures will be continuously monitored during the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Exercise level will be increased every 3 minutes until test termination criteria are achieved. Measurements will be obtained at rest, every 3 minutes during the exercise test (referred to as a stage below) and at 5 minutes post exercise. Results will be reported as a 30 second average. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).
Outcome measures
| Measure |
Riociguat 0.5 mg
n=6 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 0.5
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Riociguat 1.0 mg
n=11 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 1.0 mg
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Control Arm
n=5 Participants
No drug
After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude.
|
|---|---|---|---|
|
Mean Pulmonary Artery Pressure
No Drug: Rest
|
16.8667 mm Hg
Standard Deviation 4.82604
|
15.6545 mm Hg
Standard Deviation 4.93728
|
16.3800 mm Hg
Standard Deviation 3.11400
|
|
Mean Pulmonary Artery Pressure
After Drug: Rest
|
16.6833 mm Hg
Standard Deviation 1.41622
|
15.4900 mm Hg
Standard Deviation 5.14078
|
17.4000 mm Hg
Standard Deviation 3.57980
|
|
Mean Pulmonary Artery Pressure
No Drug: Stage 1
|
25.0000 mm Hg
Standard Deviation 3.93904
|
26.9455 mm Hg
Standard Deviation 7.21074
|
25.3600 mm Hg
Standard Deviation 5.10225
|
|
Mean Pulmonary Artery Pressure
After Drug: Stage 1
|
26.1167 mm Hg
Standard Deviation 3.09866
|
25.1545 mm Hg
Standard Deviation 6.54437
|
25.0800 mm Hg
Standard Deviation 5.02215
|
|
Mean Pulmonary Artery Pressure
No Drug: Stage 2
|
27.2800 mm Hg
Standard Deviation 2.66402
|
26.5800 mm Hg
Standard Deviation 4.53696
|
26.6600 mm Hg
Standard Deviation 4.19321
|
|
Mean Pulmonary Artery Pressure
After Drug: Stage 2
|
27.0600 mm Hg
Standard Deviation 2.38181
|
25.5100 mm Hg
Standard Deviation 4.41121
|
27.4400 mm Hg
Standard Deviation 4.26063
|
|
Mean Pulmonary Artery Pressure
No Drug: Stage 3
|
28.0200 mm Hg
Standard Deviation 2.09929
|
26.4111 mm Hg
Standard Deviation 3.68627
|
25.7000 mm Hg
Standard Deviation 1.61038
|
|
Mean Pulmonary Artery Pressure
After Drug: Stage 3
|
28.0500 mm Hg
Standard Deviation 2.59037
|
24.1375 mm Hg
Standard Deviation 3.13184
|
26.8500 mm Hg
Standard Deviation 3.60509
|
|
Mean Pulmonary Artery Pressure
No Drug: Stage 4
|
29.7400 mm Hg
Standard Deviation 3.19421
|
27.2750 mm Hg
Standard Deviation 3.72702
|
26.9750 mm Hg
Standard Deviation 1.32004
|
|
Mean Pulmonary Artery Pressure
After Drug: Stage 4
|
29.3750 mm Hg
Standard Deviation 2.38939
|
25.2167 mm Hg
Standard Deviation 3.90662
|
27.4000 mm Hg
Standard Deviation 4.27785
|
|
Mean Pulmonary Artery Pressure
No Drug: Stage 5
|
30.8400 mm Hg
Standard Deviation 2.67638
|
28.0333 mm Hg
Standard Deviation 4.54914
|
27.5000 mm Hg
Standard Deviation 0.87560
|
|
Mean Pulmonary Artery Pressure
After Drug: Stage 5
|
28.5000 mm Hg
Standard Deviation 0.42426
|
24.2000 mm Hg
Standard Deviation 3.57561
|
28.1500 mm Hg
Standard Deviation 3.63089
|
|
Mean Pulmonary Artery Pressure
No Drug: Stage 6
|
32.6500 mm Hg
Standard Deviation 3.59119
|
25.9250 mm Hg
Standard Deviation 3.73932
|
28.7667 mm Hg
Standard Deviation 2.00083
|
|
Mean Pulmonary Artery Pressure
After Drug: Stage 6
|
36.1000 mm Hg
Standard Deviation 0
|
22.7000 mm Hg
Standard Deviation 4.82563
|
29.4333 mm Hg
Standard Deviation 3.25167
|
|
Mean Pulmonary Artery Pressure
No Drug: Stage 7
|
32.9333 mm Hg
Standard Deviation 3.62537
|
20.4000 mm Hg
Standard Deviation 0.98995
|
26.6000 mm Hg
|
|
Mean Pulmonary Artery Pressure
After Drug: Stage 7
|
—
|
22.5000 mm Hg
Standard Deviation 4.38406
|
—
|
|
Mean Pulmonary Artery Pressure
No Drug: Post Exercise
|
18.9500 mm Hg
Standard Deviation 1.49766
|
19.1273 mm Hg
Standard Deviation 3.54375
|
19.3000 mm Hg
Standard Deviation 3.41541
|
|
Mean Pulmonary Artery Pressure
After Drug: Post Exercise
|
19.2167 mm Hg
Standard Deviation 3.20962
|
16.6700 mm Hg
Standard Deviation 3.53303
|
19.2800 mm Hg
Standard Deviation 3.98083
|
SECONDARY outcome
Timeframe: At rest, every 3 minutes during the exercise test and 5 minutes after each exercise testPopulation: Not all subjects performed the same number of exercise stages to achieve VO2max.
Subject systemic arterial pressures will be continuously monitored via radial artery catheterization during the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Exercise level will be increased every 3 minutes until test termination criteria are achieved. Measurements will be obtained at rest, every 3 minutes during the exercise test (referred to as a stage below) and at 5 minutes post exercise. Results will be reported as a 30 second average. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).
Outcome measures
| Measure |
Riociguat 0.5 mg
n=6 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 0.5
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Riociguat 1.0 mg
n=11 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 1.0 mg
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Control Arm
n=5 Participants
No drug
After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude.
|
|---|---|---|---|
|
Mean Radial Arterial Pressure
After Drug: Post Exercise
|
92.0833 mm Hg
Standard Deviation 5.13358
|
81.7800 mm Hg
Standard Deviation 12.2102
|
95.3600 mm Hg
Standard Deviation 13.4986
|
|
Mean Radial Arterial Pressure
No Drug: Rest
|
87.8333 mm Hg
Standard Deviation 7.50697
|
93.3182 mm Hg
Standard Deviation 6.88474
|
96.5600 mm Hg
Standard Deviation 3.94310
|
|
Mean Radial Arterial Pressure
After Drug: Rest
|
91.6000 mm Hg
Standard Deviation 6.68820
|
91.8000 mm Hg
Standard Deviation 7.96171
|
96.7600 mm Hg
Standard Deviation 7.87102
|
|
Mean Radial Arterial Pressure
No Drug: Stage 1
|
93.5167 mm Hg
Standard Deviation 9.2227
|
101.545 mm Hg
Standard Deviation 6.19231
|
100.1600 mm Hg
Standard Deviation 12.2541
|
|
Mean Radial Arterial Pressure
After Drug: Stage 1
|
97.1167 mm Hg
Standard Deviation 11.6199
|
97.627 mm Hg
Standard Deviation 7.23645
|
102.500 mm Hg
Standard Deviation 13.6998
|
|
Mean Radial Arterial Pressure
No Drug: Stage 2
|
105.480 mm Hg
Standard Deviation 7.23063
|
107.270 mm Hg
Standard Deviation 4.49074
|
107.020 mm Hg
Standard Deviation 12.4432
|
|
Mean Radial Arterial Pressure
After Drug: Stage 2
|
107.260 mm Hg
Standard Deviation 8.15494
|
104.867 mm Hg
Standard Deviation 4.38834
|
105.580 mm Hg
Standard Deviation 16.6067
|
|
Mean Radial Arterial Pressure
No Drug: Stage 3
|
107.580 mm Hg
Standard Deviation 7.0733
|
110.122 mm Hg
Standard Deviation 6.10794
|
109.425 mm Hg
Standard Deviation 14.9402
|
|
Mean Radial Arterial Pressure
After Drug: Stage 3
|
114.65 mm Hg
Standard Deviation 10.2142
|
106.425 mm Hg
Standard Deviation 6.00541
|
111.825 mm Hg
Standard Deviation 17.3803
|
|
Mean Radial Arterial Pressure
No Drug: Stage 4
|
113.140 mm Hg
Standard Deviation 7.43962
|
114.650 mm Hg
Standard Deviation 6.39710
|
112.675 mm Hg
Standard Deviation 13.6754
|
|
Mean Radial Arterial Pressure
After Drug: Stage 4
|
117.025 mm Hg
Standard Deviation 9.37386
|
109.517 mm Hg
Standard Deviation 8.24874
|
112.475 mm Hg
Standard Deviation 18.1522
|
|
Mean Radial Arterial Pressure
No Drug: Stage 5
|
116.500 mm Hg
Standard Deviation 9.67471
|
115.267 mm Hg
Standard Deviation 9.39184
|
114.775 mm Hg
Standard Deviation 12.2004
|
|
Mean Radial Arterial Pressure
After Drug: Stage 5
|
124.800 mm Hg
Standard Deviation 8.76812
|
108.240 mm Hg
Standard Deviation 9.10950
|
114.175 mm Hg
Standard Deviation 14.4756
|
|
Mean Radial Arterial Pressure
No Drug: Stage 6
|
115.900 mm Hg
Standard Deviation 13.4291
|
112.025 mm Hg
Standard Deviation 9.61852
|
108.100 mm Hg
Standard Deviation 3.89744
|
|
Mean Radial Arterial Pressure
After Drug: Stage 6
|
143.1 mm Hg
|
108.825 mm Hg
Standard Deviation 9.33323
|
107.367 mm Hg
Standard Deviation 5.40031
|
|
Mean Radial Arterial Pressure
No Drug: Stage 7
|
122.700 mm Hg
Standard Deviation 21.3551
|
107.900 mm Hg
Standard Deviation 5.23259
|
101.9 mm Hg
|
|
Mean Radial Arterial Pressure
After Drug: Stage 7
|
—
|
102.400 mm Hg
Standard Deviation 7.91960
|
—
|
|
Mean Radial Arterial Pressure
No Drug: Post Exercise
|
89.500 mm Hg
Standard Deviation 9.01665
|
90.3545 mm Hg
Standard Deviation 15.1484
|
90.4800 mm Hg
Standard Deviation 17.2794
|
SECONDARY outcome
Timeframe: At rest, every 3 minutes during the exercise test and 5 minutes after each exercise testPopulation: Not all subjects performed the same number of exercise stages to achieve VO2max.
Subject arterial oxygen saturation (SaO2) will be periodically monitored at fixed intervals via arterial blood gas measurements during the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Measurements will be obtained at rest, every 3 minutes during the exercise test (referred to as a stage below) and at 5 minutes post exercise. Results will be reported as a 30 second average. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).
Outcome measures
| Measure |
Riociguat 0.5 mg
n=6 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 0.5
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Riociguat 1.0 mg
n=11 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 1.0 mg
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Control Arm
n=5 Participants
No drug
After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude.
|
|---|---|---|---|
|
Mean Arterial Oxygen Saturation (SaO2)
No Drug: Stage 1
|
71.2800 % oxygen saturation
Standard Deviation 4.90683
|
73.1545 % oxygen saturation
Standard Deviation 7.01703
|
74.2600 % oxygen saturation
Standard Deviation 5.79552
|
|
Mean Arterial Oxygen Saturation (SaO2)
No Drug: Stage 3
|
71.5250 % oxygen saturation
Standard Deviation 2.65503
|
71.9333 % oxygen saturation
Standard Deviation 7.44681
|
67.1750 % oxygen saturation
Standard Deviation 6.63193
|
|
Mean Arterial Oxygen Saturation (SaO2)
No Drug: Post Exercise
|
76.3500 % oxygen saturation
Standard Deviation 6.30325
|
79.2182 % oxygen saturation
Standard Deviation 4.72479
|
82.0400 % oxygen saturation
Standard Deviation 4.10889
|
|
Mean Arterial Oxygen Saturation (SaO2)
After Drug: Post Exercise
|
80.5833 % oxygen saturation
Standard Deviation 5.78983
|
81.2700 % oxygen saturation
Standard Deviation 3.60341
|
83.5400 % oxygen saturation
Standard Deviation 5.50799
|
|
Mean Arterial Oxygen Saturation (SaO2)
After Drug: Stage 6
|
67.3000 % oxygen saturation
|
71.9750 % oxygen saturation
Standard Deviation 2.98035
|
64.8667 % oxygen saturation
Standard Deviation 6.24206
|
|
Mean Arterial Oxygen Saturation (SaO2)
No Drug: Rest
|
78.3333 % oxygen saturation
Standard Deviation 5.73957
|
84.9364 % oxygen saturation
Standard Deviation 6.87696
|
85.4400 % oxygen saturation
Standard Deviation 6.50215
|
|
Mean Arterial Oxygen Saturation (SaO2)
After Drug: Rest
|
81.9667 % oxygen saturation
Standard Deviation 6.93186
|
84.4000 % oxygen saturation
Standard Deviation 6.56624
|
83.9000 % oxygen saturation
Standard Deviation 3.88909
|
|
Mean Arterial Oxygen Saturation (SaO2)
After Drug: Stage 1
|
72.5800 % oxygen saturation
Standard Deviation 3.89460
|
74.0000 % oxygen saturation
Standard Deviation 7.14967
|
70.9800 % oxygen saturation
Standard Deviation 6.00267
|
|
Mean Arterial Oxygen Saturation (SaO2)
No Drug: Stage 2
|
71.0800 % oxygen saturation
Standard Deviation 0.67971
|
72.4800 % oxygen saturation
Standard Deviation 7.56862
|
70.9200 % oxygen saturation
Standard Deviation 5.23612
|
|
Mean Arterial Oxygen Saturation (SaO2)
After Drug: Stage 2
|
73.4500 % oxygen saturation
Standard Deviation 3.17753
|
74.2556 % oxygen saturation
Standard Deviation 7.88339
|
69.9800 % oxygen saturation
Standard Deviation 6.53506
|
|
Mean Arterial Oxygen Saturation (SaO2)
After Drug: Stage 3
|
72.2500 % oxygen saturation
Standard Deviation 3.79956
|
73.5000 % oxygen saturation
Standard Deviation 8.83823
|
67.7500 % oxygen saturation
Standard Deviation 7.50533
|
|
Mean Arterial Oxygen Saturation (SaO2)
No Drug: Stage 4
|
71.3400 % oxygen saturation
Standard Deviation 2.39958
|
72.1250 % oxygen saturation
Standard Deviation 7.55735
|
68.9500 % oxygen saturation
Standard Deviation 8.11521
|
|
Mean Arterial Oxygen Saturation (SaO2)
After Drug: Stage 4
|
70.9000 % oxygen saturation
Standard Deviation 2.48956
|
72.0167 % oxygen saturation
Standard Deviation 8.17103
|
68.3500 % oxygen saturation
Standard Deviation 7.91686
|
|
Mean Arterial Oxygen Saturation (SaO2)
No Drug: Stage 5
|
71.3250 % oxygen saturation
Standard Deviation 3.20975
|
69.6333 % oxygen saturation
Standard Deviation 6.37139
|
68.825 % oxygen saturation
Standard Deviation 8.07687
|
|
Mean Arterial Oxygen Saturation (SaO2)
After Drug: Stage 5
|
70.1000 % oxygen saturation
Standard Deviation 0.84853
|
72.5200 % oxygen saturation
Standard Deviation 6.68731
|
68.825 % oxygen saturation
Standard Deviation 8.26131
|
|
Mean Arterial Oxygen Saturation (SaO2)
No Drug: Stage 6
|
71.5000 % oxygen saturation
Standard Deviation 2.88560
|
71.4750 % oxygen saturation
Standard Deviation 3.61513
|
66.5000 % oxygen saturation
Standard Deviation 7.83071
|
|
Mean Arterial Oxygen Saturation (SaO2)
No Drug: Stage 7
|
73.9667 % oxygen saturation
Standard Deviation 7.80790
|
70.8500 % oxygen saturation
Standard Deviation 1.20208
|
67.7000 % oxygen saturation
|
|
Mean Arterial Oxygen Saturation (SaO2)
After Drug: Stage 7
|
—
|
68.7000 % oxygen saturation
Standard Deviation 0.14142
|
—
|
SECONDARY outcome
Timeframe: At rest, every 3 minutes during the exercise test and 5 minutes after each exercise testPopulation: Not all subjects performed the same number of exercise stages to achieve VO2max.
Subject ventilation rates will be monitored continuously using a multi-channel A/D converter (PowerLab™) connected to a personal computer, using Chart™ software (ADInstruments, Colorado Springs, CO) during the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Exercise level will be increased every 3 minutes until test termination criteria are achieved. Measurements will be obtained at rest, every 3 minutes during the exercise test (referred to as a stage below) and at 5 minutes post exercise. Results will be reported as a 30 second average. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).
Outcome measures
| Measure |
Riociguat 0.5 mg
n=6 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 0.5
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Riociguat 1.0 mg
n=11 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 1.0 mg
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Control Arm
n=5 Participants
No drug
After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude.
|
|---|---|---|---|
|
Mean Ventilation Rate
After Drug: Post Exercise
|
29.6728 L/min
Standard Deviation 11.2070
|
34.7268 L/min
Standard Deviation 13.9398
|
40.7953 L/min
Standard Deviation 6.8369
|
|
Mean Ventilation Rate
No Drug: Stage 3
|
67.3315 L/min
Standard Deviation 3.16166
|
81.5548 L/min
Standard Deviation 11.9696
|
70.9060 L/min
Standard Deviation 2.74032
|
|
Mean Ventilation Rate
No Drug: Rest
|
14.7634 L/min
Standard Deviation 2.43930
|
16.8981 L/min
Standard Deviation 5.52822
|
18.2266 L/min
Standard Deviation 5.08350
|
|
Mean Ventilation Rate
After Drug: Rest
|
17.5454 L/min
Standard Deviation 3.71867
|
18.9289 L/min
Standard Deviation 8.96658
|
16.4128 L/min
Standard Deviation 4.11186
|
|
Mean Ventilation Rate
No Drug: Stage 1
|
38.3134 L/min
Standard Deviation 8.3828
|
40.8095 L/min
Standard Deviation 9.07931
|
46.0238 L/min
Standard Deviation 5.20868
|
|
Mean Ventilation Rate
After Drug: Stage 1
|
40.3488 L/min
Standard Deviation 12.2484
|
41.3605 L/min
Standard Deviation 5.52287
|
42.0435 L/min
Standard Deviation 7.34401
|
|
Mean Ventilation Rate
No Drug: Stage 2
|
52.1473 L/min
Standard Deviation 3.73255
|
64.6476 L/min
Standard Deviation 11.3309
|
63.2124 L/min
Standard Deviation 14.8132
|
|
Mean Ventilation Rate
After Drug: Stage 2
|
59.9588 L/min
Standard Deviation 3.22699
|
61.4905 L/min
Standard Deviation 10.9421
|
60.8040 L/min
Standard Deviation 12.9110
|
|
Mean Ventilation Rate
After Drug: Stage 4
|
97.2645 L/min
Standard Deviation 9.83327
|
96.850 L/min
Standard Deviation 10.1315
|
92.8173 L/min
Standard Deviation 7.48757
|
|
Mean Ventilation Rate
No Drug: Stage 5
|
108.857 L/min
Standard Deviation 9.0793
|
132.789 L/min
Standard Deviation 19.6447
|
113.354 L/min
Standard Deviation 9.9434
|
|
Mean Ventilation Rate
After Drug: Stage 5
|
121.556 L/min
Standard Deviation 25.4212
|
126.372 L/min
Standard Deviation 11.5500
|
118.521 L/min
Standard Deviation 16.2642
|
|
Mean Ventilation Rate
No Drug: Stage 6
|
143.373 L/min
Standard Deviation 7.76136
|
153.233 L/min
Standard Deviation 19.5104
|
137.837 L/min
Standard Deviation 19.5282
|
|
Mean Ventilation Rate
After Drug: Stage 6
|
145.65 L/min
|
151.843 L/min
Standard Deviation 21.1490
|
134.869 L/min
Standard Deviation 10.3445
|
|
Mean Ventilation Rate
No Drug: Stage 7
|
156.669 L/min
Standard Deviation 14.2390
|
173.819 L/min
Standard Deviation 20.2664
|
126.447 L/min
|
|
Mean Ventilation Rate
No Drug: Post Exercise
|
32.3927 L/min
Standard Deviation 7.0137
|
38.1639 L/min
Standard Deviation 20.6608
|
41.7934 L/min
Standard Deviation 10.1981
|
|
Mean Ventilation Rate
After Drug: Stage 7
|
—
|
156.978 L/min
Standard Deviation 7.9330
|
—
|
|
Mean Ventilation Rate
After Drug: Stage 3
|
73.6560 L/min
Standard Deviation 8.62422
|
78.0649 L/min
Standard Deviation 10.5961
|
69.1603 L/min
Standard Deviation 5.38746
|
|
Mean Ventilation Rate
No Drug: Stage 4
|
89.7233 L/min
Standard Deviation 8.06763
|
102.499 L/min
Standard Deviation 13.8660
|
89.3008 L/min
Standard Deviation 5.95060
|
SECONDARY outcome
Timeframe: At rest, every 3 minutes during the exercise test and 5 minutes after each exercise testPopulation: Not all subjects performed the same number of exercise stages to achieve VO2max.
Subject work rates at exhaustion (in watts) will be continuously monitored using an ergometer (exercise bicycle) during the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Exercise level will be increased every 3 minutes until test termination criteria are achieved. Measurements will be obtained at rest, every 3 minutes during the exercise test (referred to as a stage below) and at 5 minutes post exercise. Results will be reported as a 30 second average. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).
Outcome measures
| Measure |
Riociguat 0.5 mg
n=6 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 0.5
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Riociguat 1.0 mg
n=11 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 1.0 mg
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Control Arm
n=5 Participants
No drug
After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude.
|
|---|---|---|---|
|
Mean Work Rate at Exhaustion
No Drug: Rest
|
0 watts
Standard Deviation 0
|
0 watts
Standard Deviation 0
|
0 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
After Drug: Rest
|
0 watts
Standard Deviation 0
|
0 watts
Standard Deviation 0
|
0 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
No Drug: Stage 1
|
50 watts
Standard Deviation 0
|
50 watts
Standard Deviation 0
|
50 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
After Drug: Stage 1
|
50 watts
Standard Deviation 0
|
50 watts
Standard Deviation 0
|
50 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
No Drug: Stage 2
|
75 watts
Standard Deviation 0
|
75 watts
Standard Deviation 0
|
75 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
After Drug: Stage 2
|
75 watts
Standard Deviation 0
|
75 watts
Standard Deviation 0
|
75 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
After Drug: Stage 4
|
125 watts
Standard Deviation 0
|
125 watts
Standard Deviation 0
|
125 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
No Drug: Stage 3
|
100 watts
Standard Deviation 0
|
100 watts
Standard Deviation 0
|
100 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
After Drug: Stage 3
|
100 watts
Standard Deviation 0
|
100 watts
Standard Deviation 0
|
100 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
No Drug: Stage 4
|
125 watts
Standard Deviation 0
|
125 watts
Standard Deviation 0
|
125 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
No Drug: Stage 5
|
150 watts
Standard Deviation 0
|
150 watts
Standard Deviation 0
|
150 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
After Drug: Stage 5
|
150 watts
Standard Deviation 0
|
150 watts
Standard Deviation 0
|
150 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
No Drug: Stage 6
|
175 watts
Standard Deviation 0
|
175 watts
Standard Deviation 0
|
175 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
After Drug: Stage 6
|
175 watts
Standard Deviation 0
|
175 watts
Standard Deviation 0
|
175 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
No Drug: Stage 7
|
200 watts
Standard Deviation 0
|
200 watts
Standard Deviation 0
|
200 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
After Drug: Stage 7
|
—
|
200 watts
Standard Deviation 0
|
—
|
|
Mean Work Rate at Exhaustion
No Drug: Post Exercise
|
0 watts
Standard Deviation 0
|
0 watts
Standard Deviation 0
|
0 watts
Standard Deviation 0
|
|
Mean Work Rate at Exhaustion
After Drug: Post Exercise
|
0 watts
Standard Deviation 0
|
0 watts
Standard Deviation 0
|
0 watts
Standard Deviation 0
|
SECONDARY outcome
Timeframe: At rest, every 3 minutes during the exercise test and 5 minutes after each exercise testPopulation: Not all subjects performed the same number of exercise stages to achieve VO2max.
Arterial blood samples will be obtained before, during, and after the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Exercise level will be increased every 3 minutes until test termination criteria are achieved. Samples will be obtained during the fifth minute of rest prior to exercise, during the third minute of each exercise level (referred to as stage below) and during the fifth minute post exercise. Cardiac output (CO) will be calculated using the Fick Principle: CO = V̇O2/(CaO2 - Cv̄O2) where CaO2 and Cv̄O2 represent the arterial and mixed venous oxygen content, respectively. CaO2 and CvO2 will be determined from analysis of the arterial blood samples using an IL GEM 4000 analyzer. VO2 will be reported as the final 30 secon average value of each stage. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).
Outcome measures
| Measure |
Riociguat 0.5 mg
n=6 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 0.5
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Riociguat 1.0 mg
n=11 Participants
Riociguat 0.5 mg tablets, one-time oral dose of 1.0 mg
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude 90 minutes after Riociguat administration.
|
Control Arm
n=5 Participants
No drug
After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude.
|
|---|---|---|---|
|
Cardiac Output
No Drug: Rest
|
8.11903 L/min
Standard Deviation 2.05775
|
6.60219 L/min
Standard Deviation 1.43789
|
7.53400 L/min
Standard Deviation 1.64610
|
|
Cardiac Output
No Drug: Stage 1
|
16.1241 L/min
Standard Deviation 2.92554
|
14.6762 L/min
Standard Deviation 2.51777
|
15.7480 L/min
Standard Deviation 2.80202
|
|
Cardiac Output
No Drug: Stage 2
|
18.0884 L/min
Standard Deviation 3.40527
|
16.8736 L/min
Standard Deviation 2.56218
|
17.3880 L/min
Standard Deviation 1.69665
|
|
Cardiac Output
After Drug: Stage 2
|
20.6211 L/min
Standard Deviation 6.12566
|
16.8648 L/min
Standard Deviation 2.80466
|
19.6775 L/min
Standard Deviation 2.67616
|
|
Cardiac Output
After Drug: Stage 3
|
19.5537 L/min
Standard Deviation 2.99223
|
18.0927 L/min
Standard Deviation 3.07835
|
19.7800 L/min
Standard Deviation 1.36173
|
|
Cardiac Output
After Drug: Stage 4
|
21.5792 L/min
Standard Deviation 2.97429
|
20.8798 L/min
Standard Deviation 1.16538
|
22.2100 L/min
Standard Deviation 1.67189
|
|
Cardiac Output
No Drug: Stage 6
|
25.9674 L/min
Standard Deviation 7.14490
|
22.8612 L/min
Standard Deviation 1.49355
|
20.8800 L/min
Standard Deviation 2.41851
|
|
Cardiac Output
After Drug: Stage 6
|
25.3863 L/min
|
23.0227 L/min
Standard Deviation 3.22525
|
22.5067 L/min
Standard Deviation 0.36692
|
|
Cardiac Output
No Drug: Stage 7
|
25.4212 L/min
Standard Deviation 3.49515
|
22.0850 L/min
Standard Deviation 2.55266
|
20.4400 L/min
|
|
Cardiac Output
After Drug: Stage 7
|
—
|
22.5198 L/min
Standard Deviation 5.41621
|
—
|
|
Cardiac Output
No Drug: Post Exercise
|
10.9825 L/min
Standard Deviation 3.61124
|
11.9949 L/min
Standard Deviation 4.41810
|
13.9240 L/min
Standard Deviation 4.05329
|
|
Cardiac Output
After Drug: Post Exercise
|
8.7147 L/min
Standard Deviation 1.74727
|
10.9727 L/min
Standard Deviation 5.02902
|
10.9875 L/min
Standard Deviation 2.83843
|
|
Cardiac Output
After Drug: Stage 1
|
15.5680 L/min
Standard Deviation 6.97709
|
14.7501 L/min
Standard Deviation 2.03319
|
15.2225 L/min
Standard Deviation 1.76415
|
|
Cardiac Output
After Drug: Rest
|
8.07571 L/min
Standard Deviation 1.76633
|
8.98119 L/min
Standard Deviation 2.96115
|
7.07000 L/min
Standard Deviation 0.53110
|
|
Cardiac Output
No Drug: Stage 3
|
20.9084 L/min
Standard Deviation 3.12626
|
18.4603 L/min
Standard Deviation 2.61879
|
19.7900 L/min
Standard Deviation 1.95435
|
|
Cardiac Output
No Drug: Stage 4
|
22.0844 L/min
Standard Deviation 4.94934
|
20.6738 L/min
Standard Deviation 2.60961
|
20.3775 L/min
Standard Deviation 2.39699
|
|
Cardiac Output
No Drug: Stage 5
|
25.2647 L/min
Standard Deviation 6.59397
|
22.5701 L/min
Standard Deviation 1.61837
|
22.2475 L/min
Standard Deviation 3.11597
|
|
Cardiac Output
After Drug: Stage 5
|
26.4806 L/min
Standard Deviation 3.87549
|
21.9477 L/min
Standard Deviation 1.82104
|
24.1967 L/min
Standard Deviation 0.85008
|
Adverse Events
Riociguat 0.5 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Riociguat 1.0 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Control Arm
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Riociguat 0.5 mg
n=6 participants at risk
Riociguat 0.5 mg tablets, one-time oral dose of 0.5
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. Riociguat will be administered at the 90-minute mark of this rest period. A second VO2 max test will be repeated at altitude.
|
Riociguat 1.0 mg
n=11 participants at risk
Riociguat 0.5 mg tablets, one-time oral dose of 1.0 mg
Riociguat: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. Riociguat will be administered at the 90-minute mark of this rest period. A second VO2 max test will be repeated at altitude.
|
Control Arm
n=5 participants at risk
No drug
After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. A second VO2 max test will be repeated at altitude.
|
|---|---|---|---|
|
Vascular disorders
Phlebitis
|
16.7%
1/6 • Number of events 1 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
0.00%
0/11 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
0.00%
0/5 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
|
Vascular disorders
Venous Thrombosis
|
0.00%
0/6 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
0.00%
0/11 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
20.0%
1/5 • Number of events 1 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
|
General disorders
Dizziness
|
16.7%
1/6 • Number of events 1 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
9.1%
1/11 • Number of events 1 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
20.0%
1/5 • Number of events 1 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
16.7%
1/6 • Number of events 1 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
0.00%
0/11 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
0.00%
0/5 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
|
Musculoskeletal and connective tissue disorders
Shoulder pain
|
0.00%
0/6 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
9.1%
1/11 • Number of events 1 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
0.00%
0/5 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
|
Ear and labyrinth disorders
Middle ear barotrauma
|
0.00%
0/6 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
9.1%
1/11 • Number of events 1 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
0.00%
0/5 • 1 day or anytime after that if any complaints arose potentially attributable to the study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place