Trial Outcomes & Findings for Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF (NCT NCT02742129)
NCT ID: NCT02742129
Last Updated: 2019-03-13
Results Overview
The primary endpoint will be the peak VO2 after 4 weeks treatment with inorganic nitrite as compared to the peak VO2 after 4 weeks treatment with placebo as assessed by cardiopulmonary exercise testing (CPET) performed at peak drug levels.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
105 participants
Primary outcome timeframe
End of Phase 1 & End of Phase 2
Results posted on
2019-03-13
Participant Flow
Patients with a diagnosis of HFpEF are screened for entry criteria. Willing participants meeting entry criteria will be consented and questioned to confirm that HF symptoms are the primary limitation to activity.
All consented participants continuing to meet the screening criteria will undergo a baseline HFN study-specific CPET to confirm Peak VO2 ≤75% with peak respiratory exchange ratio ≥ 1.0. All subjects that fulfill the CPET and other inclusion criteria and none of the exclusion criteria will be randomized.
Participant milestones
| Measure |
AIR001 Crossover to Placebo
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
|
Placebo Crossover to AIR001
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
|
|---|---|---|
|
Phase 1
STARTED
|
53
|
52
|
|
Phase 1
COMPLETED
|
51
|
50
|
|
Phase 1
NOT COMPLETED
|
2
|
2
|
|
Phase 2
STARTED
|
51
|
50
|
|
Phase 2
COMPLETED
|
50
|
48
|
|
Phase 2
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF
Baseline characteristics by cohort
| Measure |
AIR001 Crossover to Placebo
n=53 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally to
|
Placebo Crossover to AIR001
n=52 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally
|
Total
n=105 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
67.8 years
STANDARD_DEVIATION 8.5 • n=5 Participants
|
67.5 years
STANDARD_DEVIATION 11.6 • n=7 Participants
|
67.7 years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
53 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
104 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
47 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
92 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: End of Phase 1 & End of Phase 2Population: All patients randomized.
The primary endpoint will be the peak VO2 after 4 weeks treatment with inorganic nitrite as compared to the peak VO2 after 4 weeks treatment with placebo as assessed by cardiopulmonary exercise testing (CPET) performed at peak drug levels.
Outcome measures
| Measure |
AIR001 Crossover to Placebo
n=53 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally to
|
Placebo Crossover to AIR001
n=52 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally
|
|---|---|---|
|
Peak VO2
Phase 1
|
13.4 ml/kg/min
Standard Deviation 3.2
|
13.8 ml/kg/min
Standard Deviation 3.8
|
|
Peak VO2
Phase 2
|
13.7 ml/kg/min
Standard Deviation 3.0
|
13.6 ml/kg/min
Standard Deviation 3.6
|
SECONDARY outcome
Timeframe: End of Phase 1 & End of Phase 2Population: All patients randomized.
Average arbitrary accelerometer units (AAU) during at least 14 days and up to 21 days of the maximally tolerated dose of study drug (from 28 days post Study Visit 1 until Study Visit 2 and from 28 days post Study Visit 2 until Study Visit 3). An arbitrary accelerometer unit is calculated within the accelerometer device that is worn by the patient and represents level of activity based upon patient movement. Higher values indicate more movement. Zero indicates no movement.
Outcome measures
| Measure |
AIR001 Crossover to Placebo
n=53 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally to
|
Placebo Crossover to AIR001
n=52 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally
|
|---|---|---|
|
Average Arbitrary Accelerometer Units (AAU)
Phase 1
|
5692 accelerometry units
Standard Deviation 2886
|
5341 accelerometry units
Standard Deviation 3115
|
|
Average Arbitrary Accelerometer Units (AAU)
Phase 2
|
5688 accelerometry units
Standard Deviation 2950
|
5289 accelerometry units
Standard Deviation 2976
|
SECONDARY outcome
Timeframe: End of Phase 1 & End of Phase 2Population: All patients randomized.
To evaluate whether AIR001 improves Medial E/e' ratio (the ratio between early mitral inflow velocity and mitral annular early diastolic velocity for diastolic evaluation) in comparison to placebo.
Outcome measures
| Measure |
AIR001 Crossover to Placebo
n=53 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally to
|
Placebo Crossover to AIR001
n=52 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally
|
|---|---|---|
|
Medial E/e' Ratio as Measured by Echocardiography Core Lab
Phase 1
|
15.4 ratio
Standard Deviation 8.3
|
18.3 ratio
Standard Deviation 11.8
|
|
Medial E/e' Ratio as Measured by Echocardiography Core Lab
Phase 2
|
15.0 ratio
Standard Deviation 7.3
|
17.4 ratio
Standard Deviation 11.1
|
SECONDARY outcome
Timeframe: End of Phase 1 & End of Phase 2Population: All patients randomized.
To evaluate whether AIR001 improves Left atrial volume index in comparison to placebo.
Outcome measures
| Measure |
AIR001 Crossover to Placebo
n=53 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally to
|
Placebo Crossover to AIR001
n=52 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally
|
|---|---|---|
|
Left Atrial Volume Index as Measured by Echocardiography
Phase 1
|
36.3 ml/m^2
Standard Deviation 16.5
|
40.1 ml/m^2
Standard Deviation 20.6
|
|
Left Atrial Volume Index as Measured by Echocardiography
Phase 2
|
37.2 ml/m^2
Standard Deviation 13.9
|
39.1 ml/m^2
Standard Deviation 20.4
|
SECONDARY outcome
Timeframe: End of Phase 1 & End of Phase 2Population: All patients randomized.
To evaluate whether AIR001 improves pulmonary artery systolic pressure in comparison to placebo.
Outcome measures
| Measure |
AIR001 Crossover to Placebo
n=53 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally to
|
Placebo Crossover to AIR001
n=52 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally
|
|---|---|---|
|
Pulmonary Artery Systolic Pressure as Measured by Echocardiography
Phase 1
|
38.2 mmHg
Standard Deviation 9.7
|
39.6 mmHg
Standard Deviation 13.5
|
|
Pulmonary Artery Systolic Pressure as Measured by Echocardiography
Phase 2
|
35.0 mmHg
Standard Deviation 7.3
|
37.3 mmHg
Standard Deviation 9.2
|
SECONDARY outcome
Timeframe: End of Phase 1 & End of Phase 2Population: All patients randomized.
To evaluate whether AR001 improves quality of life in comparison to placebo. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific patient-reported outcomes measure for patients with heart failure. It consists of 23 items, is comprised of 7 clinically relevant scales (Symptom Frequency, Symptom Burden, Symptom Stability, Physical Limitation, Social Limitation, Quality of Life, and Self-Efficacy), and yields 3 summary scores (Clinical Summary, Total Symptom, and Overall Summary Scores). Scale and summary scores range between 0 and 100, with higher scores indicating better health status (eg, better functioning, fewer symptoms, better quality of life). Higher values of the overall KCCQ score are considered to be better than lower values.
Outcome measures
| Measure |
AIR001 Crossover to Placebo
n=53 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally to
|
Placebo Crossover to AIR001
n=52 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally
|
|---|---|---|
|
Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Score
Phase 1
|
65.6 units on a scale
Standard Deviation 18.8
|
59.8 units on a scale
Standard Deviation 18.4
|
|
Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Score
Phase 2
|
64.1 units on a scale
Standard Deviation 18.4
|
59.4 units on a scale
Standard Deviation 21.1
|
SECONDARY outcome
Timeframe: End of Phase 1 & End of Phase 2Population: All patients randomized.
Evaluate whether AIR001 improves natriuretic peptide levels in comparison to placebo
Outcome measures
| Measure |
AIR001 Crossover to Placebo
n=53 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally to
|
Placebo Crossover to AIR001
n=52 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally
|
|---|---|---|
|
N-terminal Pro-B-type Natriuretic Peptide Level (NT-proBNP)
Phase 2
|
513.9 pg/mL
Standard Deviation 606.0
|
545.2 pg/mL
Standard Deviation 784.5
|
|
N-terminal Pro-B-type Natriuretic Peptide Level (NT-proBNP)
Phase 1
|
494.8 pg/mL
Standard Deviation 542.3
|
550.4 pg/mL
Standard Deviation 746.5
|
SECONDARY outcome
Timeframe: End of Phase 1 & End of Phase 2Population: All patients randomized.
To evaluate whether AR001 improves NYHA Class in comparison to placebo. NYHA class was measured at the end of each phase. The site physician evaluated the patient based upon the criteria for NYHA class I-IV used by the American Heart Association. NYHA functional classification provides a way of classifying the extent of heart failure. Class I (least severe): No limitation of physical activity; Class II: Slight limitation of physical activity; Class III: Marked limitation of physical activity; Class IV (most severe): Unable to carry on any physical activity without discomfort.
Outcome measures
| Measure |
AIR001 Crossover to Placebo
n=53 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally to
|
Placebo Crossover to AIR001
n=52 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally
|
|---|---|---|
|
NYHA (New York Heart Association) Class
Phase 2 · III
|
24 Participants
|
25 Participants
|
|
NYHA (New York Heart Association) Class
Phase 1 · I
|
1 Participants
|
0 Participants
|
|
NYHA (New York Heart Association) Class
Phase 1 · II
|
21 Participants
|
29 Participants
|
|
NYHA (New York Heart Association) Class
Phase 1 · III
|
26 Participants
|
20 Participants
|
|
NYHA (New York Heart Association) Class
Phase 1 · IV
|
1 Participants
|
0 Participants
|
|
NYHA (New York Heart Association) Class
Phase 2 · I
|
0 Participants
|
1 Participants
|
|
NYHA (New York Heart Association) Class
Phase 2 · II
|
24 Participants
|
22 Participants
|
|
NYHA (New York Heart Association) Class
Phase 2 · IV
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: End of Phase 2Population: All randomized patients with available data.
Self-reported participant preference for study period 1 (Phase 1) vs. study period 2 (Phase 2)
Outcome measures
| Measure |
AIR001 Crossover to Placebo
n=48 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally to
|
Placebo Crossover to AIR001
n=47 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally
|
|---|---|---|
|
Patient Preference for AIR001 Treatment at the End of Study
Phase 1 Patient Felt Better
|
23 Participants
|
15 Participants
|
|
Patient Preference for AIR001 Treatment at the End of Study
Phase 2 Patient Felt Better
|
17 Participants
|
20 Participants
|
|
Patient Preference for AIR001 Treatment at the End of Study
No Preference
|
8 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: End of Phase 1 & End of Phase 2Population: All patients randomized.
To evaluate whether ARI001 in comparison to placebo improves ventilator efficiency as measured by Slope of Ve/VCO2 during study drug administration. The Ve/VCO2 slope is defined as the slope of the linear relationship between ventilation and carbon dioxide output and is a measure of the velocity.
Outcome measures
| Measure |
AIR001 Crossover to Placebo
n=53 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally to
|
Placebo Crossover to AIR001
n=52 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally
|
|---|---|---|
|
VE/VCO2 Slope (Ventilatory Efficiency) as Provided by Cardiopulmonary Exercise Testing Core Lab
Phase 1
|
31.8 unitless
Standard Deviation 5.7
|
33.9 unitless
Standard Deviation 6.9
|
|
VE/VCO2 Slope (Ventilatory Efficiency) as Provided by Cardiopulmonary Exercise Testing Core Lab
Phase 2
|
32.1 unitless
Standard Deviation 6.0
|
33.6 unitless
Standard Deviation 7.3
|
SECONDARY outcome
Timeframe: End of Phase 1 & End of Phase 2Population: All patients randomized.
To evaluate whether ARI001 in comparison to placebo improves submaximal exercise capacity as measured by VO2 (rate of oxygen consumption measured during incremental exercise) at ventilatory threshold during study drug administration.
Outcome measures
| Measure |
AIR001 Crossover to Placebo
n=53 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally to
|
Placebo Crossover to AIR001
n=52 Participants
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
Nebulized Sodium Nitrite: Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day. Placebo: Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally
|
|---|---|---|
|
VO2 at Ventilatory Threshold (Submaximal Exercise Capacity) as Provided by Cardiopulmonary Exercise Testing Core Lab
Phase 1
|
7.8 ml/min
Standard Deviation 1.6
|
8.0 ml/min
Standard Deviation 1.9
|
|
VO2 at Ventilatory Threshold (Submaximal Exercise Capacity) as Provided by Cardiopulmonary Exercise Testing Core Lab
Phase 2
|
7.9 ml/min
Standard Deviation 1.6
|
7.8 ml/min
Standard Deviation 1.7
|
Adverse Events
AIR001
Serious events: 5 serious events
Other events: 79 other events
Deaths: 1 deaths
Placebo
Serious events: 4 serious events
Other events: 51 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AIR001
n=103 participants at risk
Time period in which patient received AIR001 plus 2 weeks regardless of study phase.
|
Placebo
n=102 participants at risk
Time period in which patient received placebo plus 2 weeks regardless of study phase.
|
|---|---|---|
|
Gastrointestinal disorders
Crohn's Disease
|
0.97%
1/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
0.00%
0/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
General disorders
Chest Pain
|
0.97%
1/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
0.00%
0/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
General disorders
Sudden Death
|
0.97%
1/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
0.00%
0/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Injury, poisoning and procedural complications
Foreign body in gastrointestinal tract
|
0.97%
1/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
0.00%
0/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.97%
1/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
0.00%
0/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.97%
1/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
0.00%
0/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
2.0%
2/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Infections and infestations
Sepsis
|
0.00%
0/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
0.98%
1/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Infections and infestations
Staphylococcal bacteraemia
|
0.00%
0/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
0.98%
1/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
0.98%
1/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Nervous system disorders
Syncope
|
0.00%
0/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
0.98%
1/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
Other adverse events
| Measure |
AIR001
n=103 participants at risk
Time period in which patient received AIR001 plus 2 weeks regardless of study phase.
|
Placebo
n=102 participants at risk
Time period in which patient received placebo plus 2 weeks regardless of study phase.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
5.8%
6/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
0.98%
1/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
General disorders
Fatigue
|
5.8%
6/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
2.9%
3/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Nervous system disorders
Dizziness
|
16.5%
17/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
18.6%
19/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Nervous system disorders
Headache
|
6.8%
7/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
8.8%
9/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
29.1%
30/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
9.8%
10/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Respiratory, thoracic and mediastinal disorders
dsypnoea
|
10.7%
11/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
3.9%
4/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Respiratory, thoracic and mediastinal disorders
Productive Cough
|
8.7%
9/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
0.00%
0/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
9.7%
10/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
0.98%
1/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
Infections and infestations
Upper respiratory tract infection
|
4.9%
5/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
2.9%
3/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
|
General disorders
Chest discomfort
|
2.9%
3/103 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
3.9%
4/102 • Consent to 2 weeks post end of Phase 2
Per protocol, all AEs/SAEs were collected except for anticipated, disease-related events in patients with HF with preserved EF. If a patient stopped participation in the study for any reason prior to the beginning of a study phase, that patient would not be included in the denominator for the treatment received in the period that was missed.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60