Trial Outcomes & Findings for A Phase 2 Trial of IW-1973, A Stimulator of Soluble Guanylate Cyclase (sGC), in Patients With Stable Type 2 Diabetes and Hypertension (NCT NCT02906579)
NCT ID: NCT02906579
Last Updated: 2020-04-16
Results Overview
An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with study treatment. An SAE is defined as any AE occurring at any dose that results in any of the following outcomes: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical events. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
11 participants
Primary outcome timeframe
From first dose of study drug through end of trial (Day 46 [±3 days])
Results posted on
2020-04-16
Participant Flow
Participant milestones
| Measure |
All Participants
Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
|
|---|---|
|
Overall Study
STARTED
|
11
|
|
Overall Study
Completed Cycle 1 (Placebo)
|
11
|
|
Overall Study
Completed Cycle 2 (10 mg IW-1973)
|
11
|
|
Overall Study
Completed Cycle 3 (20 mg IW-1973)
|
11
|
|
Overall Study
Completed Cycle 4 (30 mg IW-1973)
|
10
|
|
Overall Study
Completed Cycle 5 (40 mg IW-1973)
|
9
|
|
Overall Study
Completed Cycle 6 (50 mg IW-1973)
|
9
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
All Participants
Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
A Phase 2 Trial of IW-1973, A Stimulator of Soluble Guanylate Cyclase (sGC), in Patients With Stable Type 2 Diabetes and Hypertension
Baseline characteristics by cohort
| Measure |
All Participants
n=11 Participants
Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
|
|---|---|
|
Age, Continuous
|
56.6 years
STANDARD_DEVIATION 6.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
5 Participants
n=5 Participants
|
|
Study Baseline: Supine systolic blood pressure
|
136.3 mmHg
STANDARD_DEVIATION 12.9 • n=5 Participants
|
|
Study Baseline: Supine diastolic blood pressure
|
80.4 mmHg
STANDARD_DEVIATION 5.9 • n=5 Participants
|
|
Study Baseline: Pulse
|
72.0 beats per minute
STANDARD_DEVIATION 15.9 • n=5 Participants
|
|
Study Baseline: Cholesterol, Glucose, HDL-C, LDL-C, Triglycerides
Cholesterol
|
185.0 mg/dL
STANDARD_DEVIATION 44.9 • n=5 Participants
|
|
Study Baseline: Cholesterol, Glucose, HDL-C, LDL-C, Triglycerides
Glucose
|
143.27 mg/dL
STANDARD_DEVIATION 34.34 • n=5 Participants
|
|
Study Baseline: Cholesterol, Glucose, HDL-C, LDL-C, Triglycerides
High-density lipoprotein cholesterol (HDL-C)
|
50.27 mg/dL
STANDARD_DEVIATION 14.11 • n=5 Participants
|
|
Study Baseline: Cholesterol, Glucose, HDL-C, LDL-C, Triglycerides
Low-density lipoprotein cholesterol (LDL-C)
|
107.45 mg/dL
STANDARD_DEVIATION 36.74 • n=5 Participants
|
|
Study Baseline: Cholesterol, Glucose, HDL-C, LDL-C, Triglycerides
Triglycerides
|
137.73 mg/dL
STANDARD_DEVIATION 54.23 • n=5 Participants
|
|
Study Baseline: Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase
GGT
|
36.2 U/L
STANDARD_DEVIATION 28.4 • n=5 Participants
|
|
Study Baseline: Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase
Lactate Dehydrogenase
|
163.1 U/L
STANDARD_DEVIATION 30.7 • n=5 Participants
|
|
Study Baseline: Hemoglobin A1c
|
7.67 percent
STANDARD_DEVIATION 1.33 • n=5 Participants
|
|
Study Baseline: Insulin
|
17.50 μIU/mL
STANDARD_DEVIATION 12.17 • n=5 Participants
|
|
Study Baseline: Respiratory Rate
|
16.4 breaths/min
STANDARD_DEVIATION 2.2 • n=5 Participants
|
|
Study Baseline: Temperature
|
36.68 degrees celcius
STANDARD_DEVIATION 0.21 • n=5 Participants
|
|
Study Baseline: Weight
|
91.08 kg
STANDARD_DEVIATION 11.58 • n=5 Participants
|
PRIMARY outcome
Timeframe: From first dose of study drug through end of trial (Day 46 [±3 days])Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with study treatment. An SAE is defined as any AE occurring at any dose that results in any of the following outcomes: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical events. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=11 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=10 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
n=9 Participants
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to TEAEs
≥1 TEAE
|
3 Participants
|
3 Participants
|
2 Participants
|
4 Participants
|
3 Participants
|
2 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to TEAEs
SAE
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to TEAEs
DCs Due to Trough Blood Pressure Decline
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to TEAEs
Deaths
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to TEAEs
Discontinuations (DCs) due to AEs
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 19Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Study baseline is defined as the Day -1 assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)
Cholesterol: Day 19/Discharge
|
141.7 mg/dL
Standard Deviation 39.6
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)
Cholesterol: Change at Day 19/Discharge
|
-43.3 mg/dL
Standard Deviation 35.1
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)
Glucose: Day 19/Discharge
|
116.82 mg/dL
Standard Deviation 25.43
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)
Glucose: Change at Day 19/Discharge
|
-26.45 mg/dL
Standard Deviation 25.25
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)
HDL-C: Day 19/Discharge
|
44.36 mg/dL
Standard Deviation 10.74
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)
HDL-C: Change at Day 19/Discharge
|
-5.91 mg/dL
Standard Deviation 7.73
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)
LDL-C: Day 19/Discharge
|
73.09 mg/dL
Standard Deviation 34.69
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)
LDL-C: Change at Day 19/Discharge
|
-34.36 mg/dL
Standard Deviation 28.88
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)
Triglycerides: Day 19/Discharge
|
121.73 mg/dL
Standard Deviation 46.10
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)
Triglycerides: Change at Day 19/Discharge
|
-16.00 mg/dL
Standard Deviation 42.45
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 32Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Study baseline is defined as the Day -1 assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)
Cholesterol: Day 32/Follow-Up
|
183.1 mg/dL
Standard Deviation 48.6
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)
Cholesterol: Change at Day 32/Follow-Up
|
-1.9 mg/dL
Standard Deviation 27.1
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)
Glucose: Day 32/Follow-Up
|
154.27 mg/dL
Standard Deviation 48.54
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)
Glucose: Change at Day 32/Follow-Up
|
11.00 mg/dL
Standard Deviation 41.47
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)
HDL-C: Day 32/Follow-Up
|
48.18 mg/dL
Standard Deviation 10.32
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)
HDL-C: Change at Day 32/Follow-Up
|
-2.09 mg/dL
Standard Deviation 6.88
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)
LDL-C: Day 32/Follow-Up
|
107.27 mg/dL
Standard Deviation 42.11
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)
LDL-C: Change at Day 32/Follow-Up
|
-0.18 mg/dL
Standard Deviation 23.84
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)
Triglycerides: Day 32/Follow-Up
|
138.09 mg/dL
Standard Deviation 46.26
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)
Triglycerides: Change at Day 32/Follow-Up
|
0.36 mg/dL
Standard Deviation 52.94
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 19Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Study baseline is defined as the Day -1 assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase at Discharge Day (Day 19)
GGT: Day 19/Discharge
|
28.3 U/L
Standard Deviation 17.2
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase at Discharge Day (Day 19)
GGT: Change at Day 19/Discharge
|
-7.9 U/L
Standard Deviation 15.9
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase at Discharge Day (Day 19)
Lactate Dehydrogenase: Day 19/Discharge
|
135.7 U/L
Standard Deviation 18.2
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase at Discharge Day (Day 19)
Lactate Dehydrogenase: Change at Day 19/Discharge
|
-27.4 U/L
Standard Deviation 21.2
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 32Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Study baseline is defined as the Day -1 assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in GGT and Lactate Dehydrogenase at Follow-Up (Day 32)
GGT: Day 32/Follow-Up
|
53.6 U/L
Standard Deviation 83.9
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in GGT and Lactate Dehydrogenase at Follow-Up (Day 32)
GGT: Change at Day 32/Follow-Up
|
17.5 U/L
Standard Deviation 67.8
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in GGT and Lactate Dehydrogenase at Follow-Up (Day 32)
Lactate Dehydrogenase: Day 32/Follow-Up
|
171.6 U/L
Standard Deviation 55.2
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in GGT and Lactate Dehydrogenase at Follow-Up (Day 32)
Lactate Dehydrogenase: Change at Day 32/Follow-Up
|
8.5 U/L
Standard Deviation 46.4
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 19Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Study baseline is defined as the Day -1 assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Discharge Day (Day 19)
Discharge Day (Day 19)
|
7.27 percent
Standard Deviation 1.53
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Discharge Day (Day 19)
Change at Discharge Day (Day 19)
|
-0.40 percent
Standard Deviation 0.54
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 32Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Study baseline is defined as the Day -1 assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Follow-Up (Day 32)
Follow-Up (Day 32)
|
7.54 percent
Standard Deviation 1.49
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Follow-Up (Day 32)
Change at Follow-Up (Day 32)
|
-0.14 percent
Standard Deviation 0.49
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 19Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Study baseline is defined as the Day -1 assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Discharge Day (Day 19)
Discharge Day (Day 19)
|
17.45 µIU/mL
Standard Deviation 14.20
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Discharge Day (Day 19)
Change at Discharge Day (Day 19)
|
-0.05 µIU/mL
Standard Deviation 5.31
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 32Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Study baseline is defined as the Day -1 assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Follow-Up (Day 32)
Follow-Up (Day 32)
|
23.81 µIU/mL
Standard Deviation 18.81
|
—
|
—
|
—
|
—
|
—
|
|
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Follow-Up (Day 32)
Change at Follow-Up (Day 32)
|
6.31 µIU/mL
Standard Deviation 11.18
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)Population: Pharmacodynamic (PD) Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.
Time-matched baseline is defined as the corresponding assessment on Day 2 of the placebo cycle. Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline in Fasting Blood Glucose on Day 2 of Each Dose Cycle
Time-Matched Baseline
|
142.3 mg/dL
Standard Deviation 32.6
|
142.3 mg/dL
Standard Deviation 32.6
|
144.1 mg/dL
Standard Deviation 33.8
|
147.7 mg/dL
Standard Deviation 33.8
|
147.7 mg/dL
Standard Deviation 33.8
|
—
|
|
Change From Time-Matched Baseline in Fasting Blood Glucose on Day 2 of Each Dose Cycle
Cycle Day 2 Change
|
-12.0 mg/dL
Standard Deviation 10.3
|
-13.4 mg/dL
Standard Deviation 9.9
|
-21.1 mg/dL
Standard Deviation 16.0
|
-24.3 mg/dL
Standard Deviation 16.9
|
-25.3 mg/dL
Standard Deviation 15.9
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)Population: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.
Time-matched baseline is defined as the corresponding assessment on Day 2 of the placebo cycle. Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline in Serum Insulin on Day 2 of Each Dose Cycle
Cycle Day 2 Change
|
0.20 µIU/mL
Standard Deviation 5.04
|
-0.40 µIU/mL
Standard Deviation 6.26
|
-2.61 µIU/mL
Standard Deviation 3.11
|
-2.49 µIU/mL
Standard Deviation 5.65
|
-2.70 µIU/mL
Standard Deviation 4.20
|
—
|
|
Change From Time-Matched Baseline in Serum Insulin on Day 2 of Each Dose Cycle
Time-Matched Baseline
|
17.35 µIU/mL
Standard Deviation 10.70
|
17.35 µIU/mL
Standard Deviation 10.70
|
17.37 µIU/mL
Standard Deviation 11.28
|
14.32 µIU/mL
Standard Deviation 6.21
|
14.32 µIU/mL
Standard Deviation 6.21
|
—
|
PRIMARY outcome
Timeframe: Up to Day 32Population: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment
Supine systolic blood pressure (SSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Supine Diastolic Blood Pressure (SDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Supine pulse rate (SPR): ≥ 110 beats per minute (bpm) and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm. Standing systolic blood pressure (StSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Standing Diastolic Blood Pressure (StDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Standing pulse rate (StPR): ≥ 110 beats per minute (bpm) and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=11 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=10 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
n=9 Participants
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Number of Participants With Notable Changes in Post Baseline Vital Signs Values
SDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Notable Changes in Post Baseline Vital Signs Values
SSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Notable Changes in Post Baseline Vital Signs Values
SSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg
|
0 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Notable Changes in Post Baseline Vital Signs Values
SDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Notable Changes in Post Baseline Vital Signs Values
SPR: ≥ 110 bpm and ↑ from BL
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Notable Changes in Post Baseline Vital Signs Values
SPR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Notable Changes in Post Baseline Vital Signs Values
StSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Notable Changes in Post Baseline Vital Signs Values
StSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Notable Changes in Post Baseline Vital Signs Values
StDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Notable Changes in Post Baseline Vital Signs Values
StDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Notable Changes in Post Baseline Vital Signs Values
StPR: ≥ 120 bpm and ↑ from BL
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Notable Changes in Post Baseline Vital Signs Values
StPR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to Day 32Population: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment
Systolic blood pressure (SBP): Decrease of \> 20 mmHg from supine to standing Diastolic blood pressure (DBP): Decrease of \> 10 mmHg from supine to standing Pulse rate (PR): Increase of \> 20 bpm from supine to standing.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=11 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=10 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
n=9 Participants
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Number of Participants With Notable Post Baseline Orthostatic Vital Signs Values
SBP: Decrease of > 20 mmHg, supine to standing
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Notable Post Baseline Orthostatic Vital Signs Values
DBP: Decrease of > 10 mmHg from supine to standin
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Notable Post Baseline Orthostatic Vital Signs Values
PR: Increase of > 20 bpm from supine to standing
|
3 Participants
|
4 Participants
|
3 Participants
|
5 Participants
|
3 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 19, Day 32Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Baseline Over Time in Respiratory Rate
Change at Day 19/Discharge
|
-0.7 breaths/min
Standard Deviation 1.8
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline Over Time in Respiratory Rate
Change at Day 32/Follow-Up
|
-1.5 breaths/min
Standard Deviation 2.7
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 19, Day 32Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Baseline Over Time in Temperature
Change at Day 19/Discharge
|
0.12 degrees celcius
Standard Deviation 0.19
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline Over Time in Temperature
Change at Day 32/Follow-Up
|
-0.03 degrees celcius
Standard Deviation 0.20
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 19, Day 32Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Baseline Over Time in Weight
Change at Day 19/Discharge
|
-3.47 kg
Standard Deviation 2.16
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline Over Time in Weight
Change at Day 32/Follow-Up
|
-1.40 kg
Standard Deviation 1.61
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Significant Findings or Shifts in Baseline in Electrocardiograms (ECGs)
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19Population: Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=11 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=10 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
n=9 Participants
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Significant Findings or Shifts in Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 hPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Study baseline is defined as the Day -1 assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=11 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=10 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
n=9 Participants
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Study Baseline Over Time in Supine Pulse
Change at Cycle Day 3, 8 h
|
-1.0 bpm
Standard Deviation 11.2
|
0.6 bpm
Standard Deviation 9.3
|
-1.6 bpm
Standard Deviation 11.7
|
-1.2 bpm
Standard Deviation 7.8
|
-0.3 bpm
Standard Deviation 11.4
|
4.2 bpm
Standard Deviation 14.8
|
|
Change From Study Baseline Over Time in Supine Pulse
Study Baseline
|
72.0 bpm
Standard Deviation 15.9
|
72.0 bpm
Standard Deviation 15.9
|
72.0 bpm
Standard Deviation 15.9
|
72.7 bpm
Standard Deviation 16.6
|
73.2 bpm
Standard Deviation 17.5
|
73.2 bpm
Standard Deviation 17.5
|
|
Change From Study Baseline Over Time in Supine Pulse
Change at Cycle Day 1, 0 h
|
-5.5 bpm
Standard Deviation 7.6
|
-6.5 bpm
Standard Deviation 11.6
|
-5.8 bpm
Standard Deviation 11.1
|
-7.2 bpm
Standard Deviation 11.0
|
-4.9 bpm
Standard Deviation 12.1
|
-6.3 bpm
Standard Deviation 13.7
|
|
Change From Study Baseline Over Time in Supine Pulse
Change at Cycle Day 1, 1 h
|
-0.1 bpm
Standard Deviation 8.7
|
-1.9 bpm
Standard Deviation 9.8
|
1.7 bpm
Standard Deviation 12.7
|
5.7 bpm
Standard Deviation 12.7
|
1.0 bpm
Standard Deviation 9.4
|
4.8 bpm
Standard Deviation 12.1
|
|
Change From Study Baseline Over Time in Supine Pulse
Change at Cycle Day 1, 2 h
|
-1.8 bpm
Standard Deviation 7.6
|
3.4 bpm
Standard Deviation 8.9
|
6.3 bpm
Standard Deviation 11.7
|
11.9 bpm
Standard Deviation 14.1
|
13.9 bpm
Standard Deviation 10.9
|
9.0 bpm
Standard Deviation 12.1
|
|
Change From Study Baseline Over Time in Supine Pulse
Change at Cycle Day 1, 4 h
|
-3.5 bpm
Standard Deviation 9.4
|
-2.2 bpm
Standard Deviation 10.7
|
1.7 bpm
Standard Deviation 9.5
|
0.7 bpm
Standard Deviation 10.6
|
3.7 bpm
Standard Deviation 7.5
|
0.2 bpm
Standard Deviation 8.8
|
|
Change From Study Baseline Over Time in Supine Pulse
Change at Cycle Day 1, 8 h
|
-3.2 bpm
Standard Deviation 9.7
|
2.1 bpm
Standard Deviation 12.3
|
0.8 bpm
Standard Deviation 10.2
|
-1.4 bpm
Standard Deviation 9.3
|
-1.7 bpm
Standard Deviation 11.7
|
-0.2 bpm
Standard Deviation 8.9
|
|
Change From Study Baseline Over Time in Supine Pulse
Change at Cycle Day 1, 12 h
|
-2.3 bpm
Standard Deviation 8.4
|
4.1 bpm
Standard Deviation 10.4
|
2.9 bpm
Standard Deviation 9.6
|
0 bpm
Standard Deviation 9.4
|
3.2 bpm
Standard Deviation 12.9
|
0.8 bpm
Standard Deviation 10.2
|
|
Change From Study Baseline Over Time in Supine Pulse
Change at Cycle Day 3, 0 h
|
-4.1 bpm
Standard Deviation 11.7
|
-6.2 bpm
Standard Deviation 10.7
|
-5.1 bpm
Standard Deviation 11.2
|
-5.4 bpm
Standard Deviation 10.8
|
-6.8 bpm
Standard Deviation 12.2
|
-6.3 bpm
Standard Deviation 11.4
|
|
Change From Study Baseline Over Time in Supine Pulse
Change at Cycle Day 3, 1 h
|
-1.8 bpm
Standard Deviation 9.3
|
3.9 bpm
Standard Deviation 11.9
|
5.5 bpm
Standard Deviation 11.7
|
6.1 bpm
Standard Deviation 8.4
|
8.8 bpm
Standard Deviation 15.2
|
10.0 bpm
Standard Deviation 13.2
|
|
Change From Study Baseline Over Time in Supine Pulse
Change at Cycle Day 3, 2 h
|
2.0 bpm
Standard Deviation 9.1
|
4.5 bpm
Standard Deviation 11.3
|
7.2 bpm
Standard Deviation 8.9
|
9.1 bpm
Standard Deviation 10.7
|
11.1 bpm
Standard Deviation 12.6
|
11.6 bpm
Standard Deviation 13.1
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 hPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Time Matched Baseline (Cycle Day 1, 0 h)
|
66.5 bpm
Standard Deviation 10.8
|
66.5 bpm
Standard Deviation 10.8
|
66.7 bpm
Standard Deviation 11.3
|
67.0 bpm
Standard Deviation 12.0
|
67.0 bpm
Standard Deviation 12.0
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Change at Cycle Day 1, 8 h
|
5.3 bpm
Standard Deviation 6.3
|
4.0 bpm
Standard Deviation 3.8
|
2.7 bpm
Standard Deviation 4.8
|
2.7 bpm
Standard Deviation 5.8
|
4.1 bpm
Standard Deviation 4.9
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Time Matched Baseline (Cycle Day 3, 1 h)
|
70.2 bpm
Standard Deviation 13.6
|
70.2 bpm
Standard Deviation 13.6
|
70.6 bpm
Standard Deviation 14.3
|
71.2 bpm
Standard Deviation 15.0
|
71.2 bpm
Standard Deviation 15.0
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Change at Cycle Day 3, 1 h
|
5.7 bpm
Standard Deviation 8.6
|
7.4 bpm
Standard Deviation 9.9
|
8.2 bpm
Standard Deviation 5.4
|
10.8 bpm
Standard Deviation 6.9
|
12.0 bpm
Standard Deviation 6.4
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Change at Cycle Day 3, 2 h
|
3.7 bpm
Standard Deviation 6.2
|
5.1 bpm
Standard Deviation 6.2
|
8.0 bpm
Standard Deviation 6.3
|
10.3 bpm
Standard Deviation 6.9
|
10.4 bpm
Standard Deviation 8.3
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Time Matched Baseline (Cycle Day 3, 8 h)
|
71.0 bpm
Standard Deviation 12.9
|
71.0 bpm
Standard Deviation 12.9
|
69.8 bpm
Standard Deviation 14.1
|
70.8 bpm
Standard Deviation 14.1
|
70.8 bpm
Standard Deviation 14.1
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Time Matched Baseline (Cycle Day 1, 8 h)
|
68.8 bpm
Standard Deviation 10.9
|
68.8 bpm
Standard Deviation 10.9
|
68.6 bpm
Standard Deviation 11.5
|
68.9 bpm
Standard Deviation 12.1
|
68.9 bpm
Standard Deviation 12.1
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Time Matched Baseline (Cycle Day 1, 12 h)
|
69.7 bpm
Standard Deviation 11.5
|
69.7 bpm
Standard Deviation 11.5
|
70.0 bpm
Standard Deviation 12.1
|
70.2 bpm
Standard Deviation 12.8
|
70.2 bpm
Standard Deviation 12.8
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Change at Cycle Day 1, 12 h
|
6.4 bpm
Standard Deviation 6.3
|
5.2 bpm
Standard Deviation 5.9
|
2.7 bpm
Standard Deviation 4.0
|
6.2 bpm
Standard Deviation 7.3
|
3.8 bpm
Standard Deviation 5.2
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Time Matched Baseline (Cycle Day 3, 0 h)
|
67.9 bpm
Standard Deviation 11.9
|
67.9 bpm
Standard Deviation 11.9
|
66.6 bpm
Standard Deviation 11.7
|
67.1 bpm
Standard Deviation 12.3
|
67.1 bpm
Standard Deviation 12.3
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Change at Cycle Day 3, 0 h
|
-2.1 bpm
Standard Deviation 4.2
|
-1.0 bpm
Standard Deviation 6.4
|
0.7 bpm
Standard Deviation 6.1
|
-0.7 bpm
Standard Deviation 2.9
|
-0.2 bpm
Standard Deviation 3.8
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Time Matched Baseline (Cycle Day 3, 2 h)
|
73.8 bpm
Standard Deviation 15.0
|
73.8 bpm
Standard Deviation 15.0
|
74.2 bpm
Standard Deviation 15.9
|
75.6 bpm
Standard Deviation 16.4
|
75.6 bpm
Standard Deviation 16.4
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Change at Cycle Day 3, 8 h
|
1.6 bpm
Standard Deviation 5.9
|
-0.6 bpm
Standard Deviation 8.4
|
-0.6 bpm
Standard Deviation 5.2
|
2.1 bpm
Standard Deviation 6.5
|
6.7 bpm
Standard Deviation 14.4
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Change at Cycle Day 1, 0 h
|
-1.1 bpm
Standard Deviation 5.5
|
-0.4 bpm
Standard Deviation 5.2
|
-1.2 bpm
Standard Deviation 5.7
|
1.3 bpm
Standard Deviation 7.0
|
-0.1 bpm
Standard Deviation 8.4
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Time Matched Baseline (Cycle Day 1, 1 h)
|
71.9 bpm
Standard Deviation 12.6
|
71.9 bpm
Standard Deviation 12.6
|
72.6 bpm
Standard Deviation 13.0
|
73.4 bpm
Standard Deviation 13.5
|
73.4 bpm
Standard Deviation 13.5
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Change at Cycle Day 1, 1 h
|
-1.8 bpm
Standard Deviation 3.2
|
1.8 bpm
Standard Deviation 5.0
|
5.8 bpm
Standard Deviation 4.7
|
0.8 bpm
Standard Deviation 4.5
|
4.6 bpm
Standard Deviation 4.3
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Time Matched Baseline (Cycle Day 1, 2 h)
|
70.2 bpm
Standard Deviation 11.7
|
70.2 bpm
Standard Deviation 11.7
|
70.8 bpm
Standard Deviation 12.2
|
71.8 bpm
Standard Deviation 12.5
|
71.8 bpm
Standard Deviation 12.5
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Change at Cycle Day 1, 2 h
|
5.2 bpm
Standard Deviation 4.3
|
8.1 bpm
Standard Deviation 6.7
|
13.8 bpm
Standard Deviation 7.2
|
15.3 bpm
Standard Deviation 7.2
|
10.4 bpm
Standard Deviation 5.8
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Time Matched Baseline (Cycle Day 1, 4 h)
|
68.5 bpm
Standard Deviation 10.4
|
68.5 bpm
Standard Deviation 10.4
|
68.3 bpm
Standard Deviation 10.9
|
68.4 bpm
Standard Deviation 11.6
|
68.4 bpm
Standard Deviation 11.6
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Change at Cycle Day 1, 4 h
|
1.3 bpm
Standard Deviation 6.2
|
5.2 bpm
Standard Deviation 7.7
|
5.1 bpm
Standard Deviation 7.5
|
8.4 bpm
Standard Deviation 6.8
|
5.0 bpm
Standard Deviation 4.5
|
—
|
PRIMARY outcome
Timeframe: Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 hPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Study baseline is defined as the Day -1 assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=11 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=10 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
n=9 Participants
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 3, 2 h
|
-16.1 mmHg
Standard Deviation 15.5
|
-23.2 mmHg
Standard Deviation 16.7
|
-27.7 mmHg
Standard Deviation 18.7
|
-28.8 mmHg
Standard Deviation 15.7
|
-28.0 mmHg
Standard Deviation 12.8
|
-26.6 mmHg
Standard Deviation 12.0
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 3, 8 h
|
-15.4 mmHg
Standard Deviation 15.0
|
-20.5 mmHg
Standard Deviation 14.6
|
-23.5 mmHg
Standard Deviation 16.3
|
-26.2 mmHg
Standard Deviation 12.5
|
-24.9 mmHg
Standard Deviation 14.3
|
-20.6 mmHg
Standard Deviation 13.5
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 1, 4 h
|
-13.5 mmHg
Standard Deviation 10.7
|
-18.4 mmHg
Standard Deviation 13.0
|
-24.4 mmHg
Standard Deviation 13.4
|
-23.9 mmHg
Standard Deviation 15.1
|
-27.0 mmHg
Standard Deviation 14.7
|
-25.3 mmHg
Standard Deviation 16.7
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 3, 0 h
|
-13.3 mmHg
Standard Deviation 15.0
|
-13.0 mmHg
Standard Deviation 16.1
|
-18.3 mmHg
Standard Deviation 16.1
|
-18.5 mmHg
Standard Deviation 15.1
|
-16.9 mmHg
Standard Deviation 11.5
|
-18.8 mmHg
Standard Deviation 16.7
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 3, 1 h
|
-16.1 mmHg
Standard Deviation 15.6
|
-22.1 mmHg
Standard Deviation 17.8
|
-24.9 mmHg
Standard Deviation 21.1
|
-26.3 mmHg
Standard Deviation 15.1
|
-24.7 mmHg
Standard Deviation 16.3
|
-25.7 mmHg
Standard Deviation 13.5
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Study Baseline
|
136.3 mmHg
Standard Deviation 12.9
|
136.3 mmHg
Standard Deviation 12.9
|
136.3 mmHg
Standard Deviation 12.9
|
133.9 mmHg
Standard Deviation 10.8
|
132.9 mmHg
Standard Deviation 10.9
|
132.9 mmHg
Standard Deviation 10.9
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 1, 0 h
|
-8.9 mmHg
Standard Deviation 9.9
|
-9.8 mmHg
Standard Deviation 19.6
|
-18.7 mmHg
Standard Deviation 16.4
|
-16.1 mmHg
Standard Deviation 10.3
|
-15.0 mmHg
Standard Deviation 14.3
|
-16.1 mmHg
Standard Deviation 15.7
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 1, 1 h
|
-14.8 mmHg
Standard Deviation 13.0
|
-18.1 mmHg
Standard Deviation 18.7
|
-25.6 mmHg
Standard Deviation 16.8
|
-24.0 mmHg
Standard Deviation 13.5
|
-22.9 mmHg
Standard Deviation 13.2
|
-27.2 mmHg
Standard Deviation 13.5
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 1, 2 h
|
-17.3 mmHg
Standard Deviation 11.5
|
-22.5 mmHg
Standard Deviation 17.8
|
-27.5 mmHg
Standard Deviation 15.7
|
-27.9 mmHg
Standard Deviation 14.5
|
-26.6 mmHg
Standard Deviation 16.8
|
-27.2 mmHg
Standard Deviation 15.1
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 1, 8 h
|
-16.6 mmHg
Standard Deviation 12.0
|
-17.7 mmHg
Standard Deviation 13.5
|
-25.3 mmHg
Standard Deviation 11.5
|
-21.7 mmHg
Standard Deviation 13.5
|
-24.3 mmHg
Standard Deviation 14.4
|
-30.6 mmHg
Standard Deviation 15.5
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 1, 12 h
|
-14.4 mmHg
Standard Deviation 12.7
|
-15.5 mmHg
Standard Deviation 16.8
|
-23.8 mmHg
Standard Deviation 13.4
|
-20.9 mmHg
Standard Deviation 14.2
|
-22.3 mmHg
Standard Deviation 15.6
|
-23.4 mmHg
Standard Deviation 17.4
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 hPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Time Matched Baseline (Cycle Day 1, 0 h)
|
127.4 mmHg
Standard Deviation 9.1
|
127.4 mmHg
Standard Deviation 9.1
|
126.3 mmHg
Standard Deviation 8.9
|
125.2 mmHg
Standard Deviation 8.7
|
125.2 mmHg
Standard Deviation 8.7
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 1, 0 h
|
-0.9 mmHg
Standard Deviation 14.0
|
-9.8 mmHg
Standard Deviation 9.9
|
-8.5 mmHg
Standard Deviation 7.9
|
-7.3 mmHg
Standard Deviation 7.4
|
-8.4 mmHg
Standard Deviation 11.8
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Time Matched Baseline (Cycle Day 1, 1 h)
|
121.5 mmHg
Standard Deviation 11.3
|
121.5 mmHg
Standard Deviation 11.3
|
121.2 mmHg
Standard Deviation 11.8
|
119.7 mmHg
Standard Deviation 11.5
|
119.7 mmHg
Standard Deviation 11.5
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 1, 1 h
|
-3.3 mmHg
Standard Deviation 12.1
|
-10.8 mmHg
Standard Deviation 11.1
|
-11.3 mmHg
Standard Deviation 10.6
|
-9.7 mmHg
Standard Deviation 11.4
|
-14.0 mmHg
Standard Deviation 11.5
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Time Matched Baseline (Cycle Day 1, 2 h)
|
119.0 mmHg
Standard Deviation 8.8
|
119.0 mmHg
Standard Deviation 8.8
|
117.6 mmHg
Standard Deviation 7.9
|
117.2 mmHg
Standard Deviation 8.3
|
117.2 mmHg
Standard Deviation 8.3
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 1, 2 h
|
-5.3 mmHg
Standard Deviation 11.4
|
-10.3 mmHg
Standard Deviation 11.4
|
-11.6 mmHg
Standard Deviation 7.5
|
-10.9 mmHg
Standard Deviation 8.1
|
-11.6 mmHg
Standard Deviation 6.8
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Time Matched Baseline (Cycle Day 1, 4 h)
|
122.7 mmHg
Standard Deviation 6.4
|
122.7 mmHg
Standard Deviation 6.4
|
121.8 mmHg
Standard Deviation 5.9
|
120.7 mmHg
Standard Deviation 4.9
|
120.7 mmHg
Standard Deviation 4.9
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 1, 4 h
|
-4.8 mmHg
Standard Deviation 8.8
|
-10.8 mmHg
Standard Deviation 11.3
|
-11.8 mmHg
Standard Deviation 11.6
|
-14.8 mmHg
Standard Deviation 10.4
|
-13.1 mmHg
Standard Deviation 10.4
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Time Matched Baseline (Cycle Day 1, 8 h)
|
119.6 mmHg
Standard Deviation 9.9
|
119.6 mmHg
Standard Deviation 9.9
|
117.3 mmHg
Standard Deviation 6.5
|
116.4 mmHg
Standard Deviation 6.3
|
116.4 mmHg
Standard Deviation 6.3
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Time Matched Baseline (Cycle Day 3, 2 h)
|
119.2 mmHg
Standard Deviation 10.8
|
119.2 mmHg
Standard Deviation 10.8
|
119.4 mmHg
Standard Deviation 11.5
|
120.4 mmHg
Standard Deviation 11.9
|
120.4 mmHg
Standard Deviation 11.9
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 3, 2 h
|
-5.5 mmHg
Standard Deviation 6.8
|
-10.4 mmHg
Standard Deviation 6.0
|
-13.9 mmHg
Standard Deviation 5.0
|
-16.3 mmHg
Standard Deviation 9.5
|
-14.8 mmHg
Standard Deviation 4.7
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 1, 8 h
|
-1.1 mmHg
Standard Deviation 12.8
|
-8.6 mmHg
Standard Deviation 11.1
|
-5.1 mmHg
Standard Deviation 11.4
|
-7.9 mmHg
Standard Deviation 11.4
|
-14.1 mmHg
Standard Deviation 9.3
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Time Matched Baseline (Cycle Day 1, 12 h)
|
121.9 mmHg
Standard Deviation 10.7
|
121.9 mmHg
Standard Deviation 10.7
|
120.7 mmHg
Standard Deviation 10.4
|
119.0 mmHg
Standard Deviation 9.5
|
119.0 mmHg
Standard Deviation 9.5
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 1, 12 h
|
-1.2 mmHg
Standard Deviation 13.7
|
-9.5 mmHg
Standard Deviation 9.8
|
-7.7 mmHg
Standard Deviation 10.7
|
-8.4 mmHg
Standard Deviation 9.2
|
-9.6 mmHg
Standard Deviation 12.5
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Time Matched Baseline (Cycle Day 3, 0 h)
|
123.0 mmHg
Standard Deviation 11.4
|
123.0 mmHg
Standard Deviation 11.4
|
124.0 mmHg
Standard Deviation 11.5
|
124.3 mmHg
Standard Deviation 12.1
|
124.3 mmHg
Standard Deviation 12.1
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 3, 0 h
|
0.3 mmHg
Standard Deviation 11.3
|
-5.0 mmHg
Standard Deviation 12.2
|
-8.6 mmHg
Standard Deviation 10.8
|
-8.3 mmHg
Standard Deviation 10.2
|
-10.2 mmHg
Standard Deviation 16.6
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Time Matched Baseline (Cycle Day 3, 1 h)
|
120.2 mmHg
Standard Deviation 12.6
|
120.2 mmHg
Standard Deviation 12.6
|
121.0 mmHg
Standard Deviation 12.9
|
121.3 mmHg
Standard Deviation 13.7
|
121.3 mmHg
Standard Deviation 13.7
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 3, 1 h
|
-6.0 mmHg
Standard Deviation 7.9
|
-8.8 mmHg
Standard Deviation 10.4
|
-13.4 mmHg
Standard Deviation 11.3
|
-13.1 mmHg
Standard Deviation 15.7
|
-14.1 mmHg
Standard Deviation 10.6
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Time Matched Baseline (Cycle Day 3, 8 h)
|
120.9 mmHg
Standard Deviation 12.0
|
120.9 mmHg
Standard Deviation 12.0
|
120.6 mmHg
Standard Deviation 13.2
|
122.1 mmHg
Standard Deviation 13.1
|
122.1 mmHg
Standard Deviation 13.1
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Change at Cycle Day 3, 8 h
|
-5.1 mmHg
Standard Deviation 10.3
|
-8.1 mmHg
Standard Deviation 9.2
|
-12.1 mmHg
Standard Deviation 10.6
|
-14.1 mmHg
Standard Deviation 10.4
|
-9.8 mmHg
Standard Deviation 13.9
|
—
|
PRIMARY outcome
Timeframe: Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 hPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Study baseline is defined as the Day -1 assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=11 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=10 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
n=9 Participants
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 1, 0 h
|
-3.3 mmHg
Standard Deviation 5.1
|
-4.4 mmHg
Standard Deviation 9.2
|
-6.9 mmHg
Standard Deviation 6.9
|
-6.4 mmHg
Standard Deviation 6.8
|
-6.3 mmHg
Standard Deviation 5.6
|
-5.9 mmHg
Standard Deviation 6.1
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 1, 1 h
|
-6.8 mmHg
Standard Deviation 6.8
|
-7.9 mmHg
Standard Deviation 8.4
|
-12.5 mmHg
Standard Deviation 8.2
|
-13.3 mmHg
Standard Deviation 7.0
|
-11.3 mmHg
Standard Deviation 5.5
|
-13.7 mmHg
Standard Deviation 6.0
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 1, 2 h
|
-8.4 mmHg
Standard Deviation 7.4
|
-10.9 mmHg
Standard Deviation 9.4
|
-12.9 mmHg
Standard Deviation 7.5
|
-16.3 mmHg
Standard Deviation 8.2
|
-11.7 mmHg
Standard Deviation 6.6
|
-13.3 mmHg
Standard Deviation 5.9
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 1, 4 h
|
-8.2 mmHg
Standard Deviation 4.9
|
-8.2 mmHg
Standard Deviation 7.3
|
-10.1 mmHg
Standard Deviation 5.8
|
-11.7 mmHg
Standard Deviation 6.6
|
-12.0 mmHg
Standard Deviation 4.9
|
-10.8 mmHg
Standard Deviation 5.5
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 1, 8 h
|
-7.2 mmHg
Standard Deviation 7.5
|
-6.7 mmHg
Standard Deviation 8.7
|
-11.5 mmHg
Standard Deviation 6.3
|
-10.1 mmHg
Standard Deviation 8.8
|
-8.4 mmHg
Standard Deviation 7.7
|
-13.3 mmHg
Standard Deviation 6.8
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 1, 12 h
|
-6.5 mmHg
Standard Deviation 6.6
|
-8.6 mmHg
Standard Deviation 8.7
|
-9.7 mmHg
Standard Deviation 10.6
|
-10.3 mmHg
Standard Deviation 9.7
|
-9.9 mmHg
Standard Deviation 6.8
|
-11.0 mmHg
Standard Deviation 9.4
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 3, 0 h
|
-4.6 mmHg
Standard Deviation 6.7
|
-2.6 mmHg
Standard Deviation 6.9
|
-5.6 mmHg
Standard Deviation 7.1
|
-7.0 mmHg
Standard Deviation 6.5
|
-7.4 mmHg
Standard Deviation 5.4
|
-5.3 mmHg
Standard Deviation 6.8
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 3, 1 h
|
-7.6 mmHg
Standard Deviation 7.9
|
-10.9 mmHg
Standard Deviation 9.1
|
-14.1 mmHg
Standard Deviation 9.6
|
-13.6 mmHg
Standard Deviation 8.8
|
-13.3 mmHg
Standard Deviation 6.3
|
-13.2 mmHg
Standard Deviation 6.3
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 3, 2 h
|
-4.8 mmHg
Standard Deviation 8.6
|
-10.5 mmHg
Standard Deviation 8.9
|
-13.5 mmHg
Standard Deviation 8.4
|
-12.3 mmHg
Standard Deviation 10.7
|
-12.2 mmHg
Standard Deviation 5.6
|
-16.3 mmHg
Standard Deviation 5.3
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Study Baseline
|
80.4 mmHg
Standard Deviation 5.9
|
80.4 mmHg
Standard Deviation 5.9
|
80.4 mmHg
Standard Deviation 5.9
|
79.9 mmHg
Standard Deviation 6.0
|
78.2 mmHg
Standard Deviation 2.9
|
78.2 mmHg
Standard Deviation 2.9
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 3, 8 h
|
-7.5 mmHg
Standard Deviation 7.8
|
-9.1 mmHg
Standard Deviation 8.5
|
-11.2 mmHg
Standard Deviation 6.2
|
-12.1 mmHg
Standard Deviation 8.3
|
-10.9 mmHg
Standard Deviation 5.3
|
-9.4 mmHg
Standard Deviation 5.6
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 hPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Time Matched Baseline (Cycle Day 1, 0 h)
|
77.1 mmHg
Standard Deviation 5.3
|
77.1 mmHg
Standard Deviation 5.3
|
77.0 mmHg
Standard Deviation 5.6
|
75.7 mmHg
Standard Deviation 3.8
|
75.7 mmHg
Standard Deviation 3.8
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 1, 0 h
|
-1.1 mmHg
Standard Deviation 6.2
|
-3.6 mmHg
Standard Deviation 3.7
|
-3.5 mmHg
Standard Deviation 4.4
|
-3.8 mmHg
Standard Deviation 2.5
|
-3.3 mmHg
Standard Deviation 4.9
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Time Matched Baseline (Cycle Day 1, 1 h)
|
73.5 mmHg
Standard Deviation 8.0
|
73.5 mmHg
Standard Deviation 8.0
|
74.1 mmHg
Standard Deviation 8.2
|
72.1 mmHg
Standard Deviation 5.6
|
72.1 mmHg
Standard Deviation 5.6
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 1, 1 h
|
-1.1 mmHg
Standard Deviation 6.5
|
-5.6 mmHg
Standard Deviation 7.4
|
-7.5 mmHg
Standard Deviation 7.3
|
-5.2 mmHg
Standard Deviation 5.3
|
-7.6 mmHg
Standard Deviation 5.8
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Time Matched Baseline (Cycle Day 1, 2 h)
|
72.0 mmHg
Standard Deviation 5.5
|
72.0 mmHg
Standard Deviation 5.5
|
71.9 mmHg
Standard Deviation 5.8
|
71.4 mmHg
Standard Deviation 5.9
|
71.4 mmHg
Standard Deviation 5.9
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 1, 2 h
|
-2.5 mmHg
Standard Deviation 6.0
|
-4.5 mmHg
Standard Deviation 5.4
|
-8.3 mmHg
Standard Deviation 4.7
|
-4.9 mmHg
Standard Deviation 6.8
|
-6.6 mmHg
Standard Deviation 5.7
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Time Matched Baseline (Cycle Day 1, 4 h)
|
72.2 mmHg
Standard Deviation 6.1
|
72.2 mmHg
Standard Deviation 6.1
|
72.5 mmHg
Standard Deviation 6.4
|
71.0 mmHg
Standard Deviation 4.5
|
71.0 mmHg
Standard Deviation 4.5
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Time Matched Baseline (Cycle Day 1, 8 h)
|
73.2 mmHg
Standard Deviation 7.3
|
73.2 mmHg
Standard Deviation 7.3
|
71.9 mmHg
Standard Deviation 6.2
|
70.9 mmHg
Standard Deviation 5.7
|
70.9 mmHg
Standard Deviation 5.7
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 1, 8 h
|
0.5 mmHg
Standard Deviation 9.9
|
-4.3 mmHg
Standard Deviation 8.4
|
-2.1 mmHg
Standard Deviation 7.9
|
-1.1 mmHg
Standard Deviation 10.6
|
-6.0 mmHg
Standard Deviation 6.2
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Time Matched Baseline (Cycle Day 1, 12 h)
|
73.8 mmHg
Standard Deviation 7.7
|
73.8 mmHg
Standard Deviation 7.7
|
72.9 mmHg
Standard Deviation 7.4
|
71.3 mmHg
Standard Deviation 5.9
|
71.3 mmHg
Standard Deviation 5.9
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Time Matched Baseline (Cycle Day 3, 1 h)
|
72.7 mmHg
Standard Deviation 6.1
|
72.7 mmHg
Standard Deviation 6.1
|
72.9 mmHg
Standard Deviation 6.3
|
72.6 mmHg
Standard Deviation 6.6
|
72.6 mmHg
Standard Deviation 6.6
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 3, 1 h
|
-3.3 mmHg
Standard Deviation 4.6
|
-6.5 mmHg
Standard Deviation 6.0
|
-6.6 mmHg
Standard Deviation 5.9
|
-7.7 mmHg
Standard Deviation 7.3
|
-7.6 mmHg
Standard Deviation 5.5
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 3, 2 h
|
-5.1 mmHg
Standard Deviation 4.0
|
-8.0 mmHg
Standard Deviation 6.4
|
-7.0 mmHg
Standard Deviation 6.2
|
-8.5 mmHg
Standard Deviation 4.9
|
-13.3 mmHg
Standard Deviation 5.1
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Time Matched Baseline (Cycle Day 3, 8 h)
|
72.8 mmHg
Standard Deviation 6.5
|
72.8 mmHg
Standard Deviation 6.5
|
73.0 mmHg
Standard Deviation 6.8
|
73.0 mmHg
Standard Deviation 6.8
|
73.0 mmHg
Standard Deviation 6.8
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 1, 4 h
|
0 mmHg
Standard Deviation 7.0
|
-1.9 mmHg
Standard Deviation 6.1
|
-4.3 mmHg
Standard Deviation 6.6
|
-4.8 mmHg
Standard Deviation 6.0
|
-3.6 mmHg
Standard Deviation 3.3
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 1, 12 h
|
-2.1 mmHg
Standard Deviation 7.2
|
-3.2 mmHg
Standard Deviation 10.7
|
-3.3 mmHg
Standard Deviation 6.8
|
-3.0 mmHg
Standard Deviation 5.4
|
-4.1 mmHg
Standard Deviation 5.6
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Time Matched Baseline (Cycle Day 3, 0 h)
|
75.7 mmHg
Standard Deviation 4.3
|
75.7 mmHg
Standard Deviation 4.3
|
76.1 mmHg
Standard Deviation 4.4
|
75.7 mmHg
Standard Deviation 4.4
|
75.7 mmHg
Standard Deviation 4.4
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 3, 0 h
|
2.0 mmHg
Standard Deviation 4.4
|
-1.0 mmHg
Standard Deviation 4.8
|
-3.2 mmHg
Standard Deviation 4.6
|
-4.9 mmHg
Standard Deviation 3.3
|
-2.8 mmHg
Standard Deviation 6.3
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Time Matched Baseline (Cycle Day 3, 2 h)
|
75.6 mmHg
Standard Deviation 6.3
|
75.6 mmHg
Standard Deviation 6.3
|
75.3 mmHg
Standard Deviation 6.7
|
75.4 mmHg
Standard Deviation 7.1
|
75.4 mmHg
Standard Deviation 7.1
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Change at Cycle Day 3, 8 h
|
-1.5 mmHg
Standard Deviation 5.5
|
-3.6 mmHg
Standard Deviation 4.0
|
-4.8 mmHg
Standard Deviation 5.3
|
-5.7 mmHg
Standard Deviation 3.9
|
-4.2 mmHg
Standard Deviation 5.5
|
—
|
PRIMARY outcome
Timeframe: Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 hPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=11 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=10 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
n=9 Participants
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Orthostatic Pulse Over Time
Cycle Day 1, Predose
|
9.7 bpm
Standard Deviation 3.8
|
11.6 bpm
Standard Deviation 5.6
|
11.0 bpm
Standard Deviation 4.1
|
11.9 bpm
Standard Deviation 3.8
|
11.0 bpm
Standard Deviation 3.9
|
10.4 bpm
Standard Deviation 2.7
|
|
Orthostatic Pulse Over Time
Cycle Day 1, 1 h
|
9.7 bpm
Standard Deviation 5.4
|
11.5 bpm
Standard Deviation 7.1
|
12.6 bpm
Standard Deviation 6.4
|
17.8 bpm
Standard Deviation 6.1
|
17.8 bpm
Standard Deviation 7.6
|
16.0 bpm
Standard Deviation 7.4
|
|
Orthostatic Pulse Over Time
Cycle Day 1, 2 h
|
10.9 bpm
Standard Deviation 4.1
|
10.6 bpm
Standard Deviation 5.9
|
12.3 bpm
Standard Deviation 8.4
|
14.6 bpm
Standard Deviation 6.8
|
13.9 bpm
Standard Deviation 5.9
|
15.6 bpm
Standard Deviation 5.7
|
|
Orthostatic Pulse Over Time
Cycle Day 1, 4 h
|
9.5 bpm
Standard Deviation 7.7
|
10.3 bpm
Standard Deviation 9.5
|
11.0 bpm
Standard Deviation 6.4
|
14.6 bpm
Standard Deviation 5.3
|
12.3 bpm
Standard Deviation 9.3
|
14.8 bpm
Standard Deviation 8.0
|
|
Orthostatic Pulse Over Time
Cycle Day 1, 8 h
|
10.8 bpm
Standard Deviation 7.8
|
10.3 bpm
Standard Deviation 6.7
|
12.7 bpm
Standard Deviation 6.5
|
13.0 bpm
Standard Deviation 3.4
|
15.2 bpm
Standard Deviation 4.4
|
11.0 bpm
Standard Deviation 7.6
|
|
Orthostatic Pulse Over Time
Cycle Day 1, 12 h
|
10.7 bpm
Standard Deviation 4.8
|
10.6 bpm
Standard Deviation 5.1
|
9.9 bpm
Standard Deviation 13.0
|
10.8 bpm
Standard Deviation 7.5
|
13.0 bpm
Standard Deviation 7.4
|
11.3 bpm
Standard Deviation 6.8
|
PRIMARY outcome
Timeframe: Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 hPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=11 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=10 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
n=9 Participants
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Orthostatic Systolic Blood Pressure Over Time
Cycle Day 1, 12 h
|
9.7 mmHg
Standard Deviation 10.5
|
6.2 mmHg
Standard Deviation 5.3
|
6.0 mmHg
Standard Deviation 6.1
|
8.0 mmHg
Standard Deviation 6.7
|
2.1 mmHg
Standard Deviation 4.5
|
3.4 mmHg
Standard Deviation 7.9
|
|
Orthostatic Systolic Blood Pressure Over Time
Cycle Day 1, Predose
|
4.4 mmHg
Standard Deviation 7.2
|
3.7 mmHg
Standard Deviation 6.5
|
5.9 mmHg
Standard Deviation 7.3
|
4.0 mmHg
Standard Deviation 13.0
|
3.4 mmHg
Standard Deviation 5.3
|
4.2 mmHg
Standard Deviation 9.1
|
|
Orthostatic Systolic Blood Pressure Over Time
Cycle Day 1, 1 h
|
7.0 mmHg
Standard Deviation 5.6
|
9.1 mmHg
Standard Deviation 8.4
|
5.2 mmHg
Standard Deviation 3.5
|
5.8 mmHg
Standard Deviation 8.2
|
4.0 mmHg
Standard Deviation 6.8
|
6.2 mmHg
Standard Deviation 6.7
|
|
Orthostatic Systolic Blood Pressure Over Time
Cycle Day 1, 2 h
|
8.5 mmHg
Standard Deviation 12.4
|
8.2 mmHg
Standard Deviation 4.6
|
6.2 mmHg
Standard Deviation 8.7
|
7.3 mmHg
Standard Deviation 8.4
|
3.3 mmHg
Standard Deviation 6.5
|
4.6 mmHg
Standard Deviation 8.3
|
|
Orthostatic Systolic Blood Pressure Over Time
Cycle Day 1, 4 h
|
3.6 mmHg
Standard Deviation 9.2
|
3.2 mmHg
Standard Deviation 8.7
|
4.2 mmHg
Standard Deviation 5.8
|
4.3 mmHg
Standard Deviation 5.0
|
6.3 mmHg
Standard Deviation 9.2
|
6.7 mmHg
Standard Deviation 7.7
|
|
Orthostatic Systolic Blood Pressure Over Time
Cycle Day 1, 8 h
|
8.4 mmHg
Standard Deviation 5.8
|
5.4 mmHg
Standard Deviation 5.8
|
8.1 mmHg
Standard Deviation 14.1
|
5.5 mmHg
Standard Deviation 7.8
|
5.6 mmHg
Standard Deviation 4.9
|
8.0 mmHg
Standard Deviation 4.5
|
PRIMARY outcome
Timeframe: Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 hPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=11 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=10 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
n=9 Participants
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Orthostatic Diastolic Blood Pressure Over Time
Cycle Day 1, Predose
|
7.0 mmHg
Standard Deviation 2.4
|
9.3 mmHg
Standard Deviation 4.7
|
8.1 mmHg
Standard Deviation 7.7
|
5.7 mmHg
Standard Deviation 5.1
|
8.3 mmHg
Standard Deviation 2.7
|
7.4 mmHg
Standard Deviation 4.4
|
|
Orthostatic Diastolic Blood Pressure Over Time
Cycle Day 1, 1 h
|
6.9 mmHg
Standard Deviation 4.1
|
7.0 mmHg
Standard Deviation 3.9
|
6.5 mmHg
Standard Deviation 3.7
|
4.7 mmHg
Standard Deviation 4.4
|
5.7 mmHg
Standard Deviation 3.6
|
5.8 mmHg
Standard Deviation 3.8
|
|
Orthostatic Diastolic Blood Pressure Over Time
Cycle Day 1, 2 h
|
10.5 mmHg
Standard Deviation 6.5
|
8.3 mmHg
Standard Deviation 3.5
|
6.5 mmHg
Standard Deviation 5.6
|
7.6 mmHg
Standard Deviation 3.7
|
3.2 mmHg
Standard Deviation 7.2
|
4.2 mmHg
Standard Deviation 4.6
|
|
Orthostatic Diastolic Blood Pressure Over Time
Cycle Day 1, 4 h
|
9.1 mmHg
Standard Deviation 3.6
|
6.6 mmHg
Standard Deviation 7.8
|
4.9 mmHg
Standard Deviation 4.3
|
5.1 mmHg
Standard Deviation 3.1
|
6.2 mmHg
Standard Deviation 2.7
|
6.9 mmHg
Standard Deviation 5.5
|
|
Orthostatic Diastolic Blood Pressure Over Time
Cycle Day 1, 8 h
|
9.1 mmHg
Standard Deviation 7.1
|
6.0 mmHg
Standard Deviation 5.5
|
7.9 mmHg
Standard Deviation 5.2
|
5.5 mmHg
Standard Deviation 3.4
|
4.7 mmHg
Standard Deviation 7.6
|
7.0 mmHg
Standard Deviation 5.0
|
|
Orthostatic Diastolic Blood Pressure Over Time
Cycle Day 1, 12 h
|
8.6 mmHg
Standard Deviation 7.7
|
7.9 mmHg
Standard Deviation 3.9
|
5.5 mmHg
Standard Deviation 6.2
|
9.3 mmHg
Standard Deviation 6.3
|
6.6 mmHg
Standard Deviation 2.5
|
6.2 mmHg
Standard Deviation 4.3
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrsPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=10 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=10 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure
0-4 hrs: Time Matched Baseline
|
125.67 mmHg
Standard Deviation 10.39
|
125.67 mmHg
Standard Deviation 10.39
|
125.67 mmHg
Standard Deviation 10.39
|
125.72 mmHg
Standard Deviation 11.02
|
125.72 mmHg
Standard Deviation 11.02
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure
0-4 hrs: Cycle Day 2 Change
|
-5.18 mmHg
Standard Deviation 5.70
|
-10.57 mmHg
Standard Deviation 8.67
|
-8.98 mmHg
Standard Deviation 9.08
|
-11.57 mmHg
Standard Deviation 11.00
|
-13.15 mmHg
Standard Deviation 12.59
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure
4-8 hrs: Time Matched Baseline
|
124.28 mmHg
Standard Deviation 8.07
|
124.28 mmHg
Standard Deviation 8.07
|
124.28 mmHg
Standard Deviation 8.07
|
123.32 mmHg
Standard Deviation 7.94
|
123.32 mmHg
Standard Deviation 7.94
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure
8-12 hrs: Time Matched Baseline
|
128.95 mmHg
Standard Deviation 9.99
|
128.95 mmHg
Standard Deviation 9.99
|
128.95 mmHg
Standard Deviation 9.99
|
127.42 mmHg
Standard Deviation 9.26
|
127.42 mmHg
Standard Deviation 9.26
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure
8-12 hrs: Cycle Day 2 Change
|
-2.65 mmHg
Standard Deviation 12.85
|
-8.80 mmHg
Standard Deviation 14.91
|
-6.81 mmHg
Standard Deviation 10.27
|
-10.51 mmHg
Standard Deviation 12.34
|
-11.93 mmHg
Standard Deviation 13.47
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure
4-8 hrs: Cycle Day 2 Change
|
-5.56 mmHg
Standard Deviation 10.61
|
-9.45 mmHg
Standard Deviation 9.68
|
-9.03 mmHg
Standard Deviation 12.55
|
-13.26 mmHg
Standard Deviation 11.78
|
-14.18 mmHg
Standard Deviation 10.07
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrsPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=10 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=10 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
3 hrs: Time Matched Baseline
|
119.10 mmHg
Standard Deviation 13.04
|
119.10 mmHg
Standard Deviation 13.04
|
119.10 mmHg
Standard Deviation 13.04
|
118.78 mmHg
Standard Deviation 13.79
|
118.78 mmHg
Standard Deviation 13.79
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
3 hrs: Cycle Day 2 Change
|
-3.20 mmHg
Standard Deviation 16.29
|
-6.40 mmHg
Standard Deviation 19.78
|
-4.70 mmHg
Standard Deviation 17.61
|
-8.22 mmHg
Standard Deviation 18.77
|
-11.56 mmHg
Standard Deviation 18.42
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
5 hrs: Time Matched Baseline
|
120.80 mmHg
Standard Deviation 14.44
|
120.80 mmHg
Standard Deviation 14.44
|
120.80 mmHg
Standard Deviation 14.44
|
119.56 mmHg
Standard Deviation 14.73
|
119.56 mmHg
Standard Deviation 14.73
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
5.5 hrs: Time Matched Baseline
|
123.50 mmHg
Standard Deviation 16.18
|
123.50 mmHg
Standard Deviation 16.18
|
123.50 mmHg
Standard Deviation 16.18
|
123.33 mmHg
Standard Deviation 17.15
|
123.33 mmHg
Standard Deviation 17.15
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
6 hrs: Time Matched Baseline
|
122.00 mmHg
Standard Deviation 11.27
|
124.89 mmHg
Standard Deviation 7.01
|
122.00 mmHg
Standard Deviation 11.27
|
120.78 mmHg
Standard Deviation 11.23
|
120.78 mmHg
Standard Deviation 11.23
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
6 hrs: Cycle Day 2 Change
|
-6.90 mmHg
Standard Deviation 16.04
|
-12.00 mmHg
Standard Deviation 11.86
|
-7.80 mmHg
Standard Deviation 13.80
|
-15.33 mmHg
Standard Deviation 17.73
|
-16.11 mmHg
Standard Deviation 14.48
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
6.5 hrs: Cycle Day 2 Change
|
-2.00 mmHg
Standard Deviation 17.95
|
-7.60 mmHg
Standard Deviation 15.90
|
-4.60 mmHg
Standard Deviation 17.60
|
-12.44 mmHg
Standard Deviation 18.41
|
-14.44 mmHg
Standard Deviation 13.97
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
7 hrs: Time Matched Baseline
|
125.50 mmHg
Standard Deviation 10.17
|
125.50 mmHg
Standard Deviation 10.17
|
125.50 mmHg
Standard Deviation 10.17
|
126.22 mmHg
Standard Deviation 10.51
|
126.22 mmHg
Standard Deviation 10.51
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
7 hrs: Cycle Day 2 Change
|
-5.50 mmHg
Standard Deviation 13.88
|
-11.60 mmHg
Standard Deviation 15.28
|
-10.70 mmHg
Standard Deviation 16.34
|
-15.44 mmHg
Standard Deviation 13.46
|
-13.78 mmHg
Standard Deviation 11.36
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
7.5 hrs: Cycle Day 2 Change
|
-8.00 mmHg
Standard Deviation 16.80
|
-12.30 mmHg
Standard Deviation 17.75
|
-12.30 mmHg
Standard Deviation 21.43
|
-16.56 mmHg
Standard Deviation 22.57
|
-14.33 mmHg
Standard Deviation 20.27
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
8 hrs: Time Matched Baseline
|
124.90 mmHg
Standard Deviation 12.68
|
124.90 mmHg
Standard Deviation 12.68
|
124.90 mmHg
Standard Deviation 12.68
|
122.44 mmHg
Standard Deviation 10.63
|
122.44 mmHg
Standard Deviation 10.63
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
8 hrs: Cycle Day 2 Change
|
-6.40 mmHg
Standard Deviation 21.29
|
-9.10 mmHg
Standard Deviation 13.54
|
-7.70 mmHg
Standard Deviation 19.81
|
-12.11 mmHg
Standard Deviation 22.83
|
-12.22 mmHg
Standard Deviation 15.70
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
8.5 hrs: Time Matched Baseline
|
126.10 mmHg
Standard Deviation 12.13
|
126.10 mmHg
Standard Deviation 12.13
|
125.11 mmHg
Standard Deviation 12.43
|
123.89 mmHg
Standard Deviation 10.52
|
123.89 mmHg
Standard Deviation 10.52
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
4 hrs: Time Matched Baseline
|
126.30 mmHg
Standard Deviation 12.57
|
126.30 mmHg
Standard Deviation 12.57
|
123.78 mmHg
Standard Deviation 10.31
|
127.56 mmHg
Standard Deviation 12.65
|
127.56 mmHg
Standard Deviation 12.65
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
4 hrs: Cycle Day 2 Change
|
-8.00 mmHg
Standard Deviation 8.94
|
-11.30 mmHg
Standard Deviation 12.70
|
-5.56 mmHg
Standard Deviation 13.31
|
-13.78 mmHg
Standard Deviation 12.66
|
-15.33 mmHg
Standard Deviation 18.41
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
4.5 hrs: Time Matched Baseline
|
129.80 mmHg
Standard Deviation 13.60
|
129.80 mmHg
Standard Deviation 13.60
|
129.80 mmHg
Standard Deviation 13.60
|
127.33 mmHg
Standard Deviation 11.82
|
127.33 mmHg
Standard Deviation 11.82
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
4.5 hrs: Cycle Day 2 Change
|
-10.70 mmHg
Standard Deviation 11.98
|
-10.50 mmHg
Standard Deviation 14.69
|
-14.70 mmHg
Standard Deviation 10.71
|
-8.78 mmHg
Standard Deviation 11.20
|
-13.44 mmHg
Standard Deviation 17.40
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
5 hrs: Cycle Day 2 Change
|
-1.90 mmHg
Standard Deviation 13.89
|
-6.20 mmHg
Standard Deviation 14.54
|
-5.20 mmHg
Standard Deviation 19.86
|
-7.33 mmHg
Standard Deviation 17.33
|
-11.67 mmHg
Standard Deviation 17.43
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
5.5 hrs: Cycle Day 2 Change
|
-3.10 mmHg
Standard Deviation 15.74
|
-9.40 mmHg
Standard Deviation 14.95
|
-9.20 mmHg
Standard Deviation 14.90
|
-18.11 mmHg
Standard Deviation 19.66
|
-17.44 mmHg
Standard Deviation 20.73
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
6.5 hrs: Time Matched Baseline
|
121.40 mmHg
Standard Deviation 7.68
|
121.40 mmHg
Standard Deviation 7.68
|
121.40 mmHg
Standard Deviation 7.68
|
121.44 mmHg
Standard Deviation 8.14
|
121.44 mmHg
Standard Deviation 8.14
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
7.5 hrs: Time Matched Baseline
|
126.30 mmHg
Standard Deviation 12.31
|
126.30 mmHg
Standard Deviation 12.31
|
126.30 mmHg
Standard Deviation 12.31
|
125.44 mmHg
Standard Deviation 12.74
|
125.44 mmHg
Standard Deviation 12.74
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
2 hrs: Cycle Day 2 Change
|
-5.10 mmHg
Standard Deviation 14.42
|
-6.30 mmHg
Standard Deviation 10.56
|
-8.90 mmHg
Standard Deviation 9.92
|
-12.56 mmHg
Standard Deviation 13.25
|
-13.11 mmHg
Standard Deviation 16.32
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
8.5 hrs: Cycle Day 2 Change
|
-5.00 mmHg
Standard Deviation 13.32
|
-8.40 mmHg
Standard Deviation 17.58
|
-1.33 mmHg
Standard Deviation 9.42
|
-12.11 mmHg
Standard Deviation 16.97
|
-12.11 mmHg
Standard Deviation 17.51
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
9 hrs: Time Matched Baseline
|
127.20 mmHg
Standard Deviation 11.12
|
127.20 mmHg
Standard Deviation 11.12
|
127.20 mmHg
Standard Deviation 11.12
|
125.67 mmHg
Standard Deviation 10.62
|
125.67 mmHg
Standard Deviation 10.62
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
9 hrs: Cycle Day 2 Change
|
-2.60 mmHg
Standard Deviation 17.44
|
-7.90 mmHg
Standard Deviation 21.66
|
-7.20 mmHg
Standard Deviation 18.33
|
-13.78 mmHg
Standard Deviation 19.77
|
-15.44 mmHg
Standard Deviation 15.16
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
9.5 hrs: Time Matched Baseline
|
128.30 mmHg
Standard Deviation 14.38
|
128.30 mmHg
Standard Deviation 14.38
|
128.30 mmHg
Standard Deviation 14.38
|
126.78 mmHg
Standard Deviation 14.38
|
126.78 mmHg
Standard Deviation 14.38
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
9.5 hrs: Cycle Day 2 Change
|
-1.90 mmHg
Standard Deviation 23.19
|
-14.00 mmHg
Standard Deviation 22.14
|
-4.70 mmHg
Standard Deviation 18.69
|
-12.11 mmHg
Standard Deviation 22.79
|
-11.56 mmHg
Standard Deviation 19.64
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
10 hrs: Time Matched Baseline
|
128.56 mmHg
Standard Deviation 14.78
|
128.56 mmHg
Standard Deviation 14.78
|
128.56 mmHg
Standard Deviation 14.78
|
126.50 mmHg
Standard Deviation 14.36
|
126.50 mmHg
Standard Deviation 14.36
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
10 hrs: Cycle Day 2 Change
|
-2.78 mmHg
Standard Deviation 20.11
|
-10.67 mmHg
Standard Deviation 19.54
|
-5.44 mmHg
Standard Deviation 13.42
|
-9.63 mmHg
Standard Deviation 22.49
|
-4.25 mmHg
Standard Deviation 24.81
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
10.5 hrs: Time Matched Baseline
|
136.90 mmHg
Standard Deviation 19.17
|
137.89 mmHg
Standard Deviation 20.07
|
136.90 mmHg
Standard Deviation 19.17
|
133.33 mmHg
Standard Deviation 16.45
|
133.33 mmHg
Standard Deviation 16.45
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
10.5 hrs: Cycle Day 2 Change
|
-5.20 mmHg
Standard Deviation 22.09
|
-5.78 mmHg
Standard Deviation 18.03
|
-8.10 mmHg
Standard Deviation 16.13
|
-11.33 mmHg
Standard Deviation 11.96
|
-11.78 mmHg
Standard Deviation 16.28
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
11 hrs: Time Matched Baseline
|
133.44 mmHg
Standard Deviation 14.97
|
133.70 mmHg
Standard Deviation 14.13
|
133.44 mmHg
Standard Deviation 14.97
|
133.11 mmHg
Standard Deviation 14.86
|
133.11 mmHg
Standard Deviation 14.86
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
11 hrs: Cycle Day 2 Change
|
-3.00 mmHg
Standard Deviation 16.05
|
-15.50 mmHg
Standard Deviation 11.64
|
-12.56 mmHg
Standard Deviation 9.17
|
-15.78 mmHg
Standard Deviation 16.54
|
-19.00 mmHg
Standard Deviation 21.04
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
11.5 hrs: Time Matched Baseline
|
126.30 mmHg
Standard Deviation 10.04
|
126.30 mmHg
Standard Deviation 10.04
|
126.30 mmHg
Standard Deviation 10.04
|
126.11 mmHg
Standard Deviation 10.64
|
126.11 mmHg
Standard Deviation 10.64
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
11.5 hrs: Cycle Day 2 Change
|
-3.20 mmHg
Standard Deviation 8.40
|
-3.20 mmHg
Standard Deviation 12.93
|
-8.70 mmHg
Standard Deviation 6.06
|
-4.56 mmHg
Standard Deviation 8.26
|
-12.22 mmHg
Standard Deviation 14.01
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
12 hrs: Time Matched Baseline
|
124.05 mmHg
Standard Deviation 9.42
|
124.05 mmHg
Standard Deviation 9.42
|
124.05 mmHg
Standard Deviation 9.42
|
123.17 mmHg
Standard Deviation 9.55
|
123.17 mmHg
Standard Deviation 9.55
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
12 hrs: Cycle Day 2 Change
|
3.45 mmHg
Standard Deviation 9.54
|
-4.10 mmHg
Standard Deviation 13.33
|
-2.55 mmHg
Standard Deviation 10.93
|
-4.94 mmHg
Standard Deviation 7.27
|
-6.72 mmHg
Standard Deviation 14.85
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
0.5 hr: Time Matched Baseline
|
140.30 mmHg
Standard Deviation 18.66
|
140.30 mmHg
Standard Deviation 18.66
|
140.30 mmHg
Standard Deviation 18.66
|
138.22 mmHg
Standard Deviation 18.53
|
138.22 mmHg
Standard Deviation 18.53
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
0.5 hr: Cycle Day 2 Change
|
-4.90 mmHg
Standard Deviation 6.89
|
-14.80 mmHg
Standard Deviation 8.78
|
-10.10 mmHg
Standard Deviation 10.09
|
-11.67 mmHg
Standard Deviation 13.06
|
-10.67 mmHg
Standard Deviation 9.95
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
1 hr: Time Matched Baseline
|
128.60 mmHg
Standard Deviation 12.56
|
128.60 mmHg
Standard Deviation 12.56
|
128.60 mmHg
Standard Deviation 12.56
|
128.89 mmHg
Standard Deviation 13.29
|
128.89 mmHg
Standard Deviation 13.29
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
1 hr: Cycle Day 2 Change
|
-7.70 mmHg
Standard Deviation 12.36
|
-12.50 mmHg
Standard Deviation 14.00
|
-10.80 mmHg
Standard Deviation 16.19
|
-8.56 mmHg
Standard Deviation 17.41
|
-14.22 mmHg
Standard Deviation 15.74
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
1.5 hrs: Time Matched Baseline
|
125.10 mmHg
Standard Deviation 13.99
|
125.10 mmHg
Standard Deviation 13.99
|
125.10 mmHg
Standard Deviation 13.99
|
125.67 mmHg
Standard Deviation 14.71
|
125.67 mmHg
Standard Deviation 14.71
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
1.5 hrs: Cycle Day 2 Change
|
-5.00 mmHg
Standard Deviation 11.75
|
-9.10 mmHg
Standard Deviation 18.46
|
-10.40 mmHg
Standard Deviation 14.39
|
-14.33 mmHg
Standard Deviation 12.71
|
-13.67 mmHg
Standard Deviation 16.81
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
2 hrs: Time Matched Baseline
|
122.70 mmHg
Standard Deviation 10.68
|
122.70 mmHg
Standard Deviation 10.68
|
122.70 mmHg
Standard Deviation 10.68
|
123.22 mmHg
Standard Deviation 11.19
|
123.22 mmHg
Standard Deviation 11.19
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
2.5 hrs: Time Matched Baseline
|
120.20 mmHg
Standard Deviation 6.05
|
120.20 mmHg
Standard Deviation 6.05
|
120.20 mmHg
Standard Deviation 6.05
|
120.22 mmHg
Standard Deviation 6.42
|
120.22 mmHg
Standard Deviation 6.42
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
2.5 hrs: Cycle Day 2 Change
|
0 mmHg
Standard Deviation 13.55
|
-10.10 mmHg
Standard Deviation 12.56
|
-7.40 mmHg
Standard Deviation 12.81
|
-13.11 mmHg
Standard Deviation 13.16
|
-12.33 mmHg
Standard Deviation 12.11
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
3.5 hrs: Time Matched Baseline
|
120.89 mmHg
Standard Deviation 13.77
|
120.89 mmHg
Standard Deviation 13.77
|
120.89 mmHg
Standard Deviation 13.77
|
120.75 mmHg
Standard Deviation 14.71
|
120.75 mmHg
Standard Deviation 14.71
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
3.5 hrs: Cycle Day 2 Change
|
-6.56 mmHg
Standard Deviation 15.95
|
-14.11 mmHg
Standard Deviation 14.29
|
-10.67 mmHg
Standard Deviation 12.36
|
-9.25 mmHg
Standard Deviation 19.03
|
-12.88 mmHg
Standard Deviation 22.40
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 2Population: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=10 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=10 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
Time-Matched Baseline
|
126.27 mmHg
Standard Deviation 8.62
|
126.27 mmHg
Standard Deviation 8.62
|
126.27 mmHg
Standard Deviation 8.62
|
125.45 mmHg
Standard Deviation 8.72
|
125.45 mmHg
Standard Deviation 8.72
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
Cycle Day 2 Change
|
-4.42 mmHg
Standard Deviation 8.59
|
-9.55 mmHg
Standard Deviation 9.98
|
-8.22 mmHg
Standard Deviation 9.74
|
-11.74 mmHg
Standard Deviation 10.71
|
-13.05 mmHg
Standard Deviation 10.66
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrsPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=10 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=10 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure
4-8 hrs: Cycle Day 2 Change
|
-2.28 mmHg
Standard Deviation 7.46
|
-4.03 mmHg
Standard Deviation 6.37
|
-3.49 mmHg
Standard Deviation 8.91
|
-7.61 mmHg
Standard Deviation 5.88
|
-5.92 mmHg
Standard Deviation 7.12
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure
0-4 hrs: Time Matched Baseline
|
75.59 mmHg
Standard Deviation 6.05
|
75.59 mmHg
Standard Deviation 6.05
|
75.59 mmHg
Standard Deviation 6.05
|
74.94 mmHg
Standard Deviation 6.04
|
74.94 mmHg
Standard Deviation 6.04
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure
0-4 hrs: Cycle Day 2 Change
|
-2.96 mmHg
Standard Deviation 3.75
|
-7.59 mmHg
Standard Deviation 6.04
|
-5.96 mmHg
Standard Deviation 5.53
|
-7.94 mmHg
Standard Deviation 4.75
|
-8.32 mmHg
Standard Deviation 6.28
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure
4-8 hrs: Time Matched Baseline
|
74.54 mmHg
Standard Deviation 7.54
|
74.54 mmHg
Standard Deviation 7.54
|
74.54 mmHg
Standard Deviation 7.54
|
72.88 mmHg
Standard Deviation 5.74
|
72.88 mmHg
Standard Deviation 5.74
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure
8-12 hrs: Time Matched Baseline
|
77.05 mmHg
Standard Deviation 6.31
|
77.05 mmHg
Standard Deviation 6.31
|
77.05 mmHg
Standard Deviation 6.31
|
75.75 mmHg
Standard Deviation 5.08
|
75.75 mmHg
Standard Deviation 5.08
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure
8-12 hrs: Cycle Day 2 Change
|
1.41 mmHg
Standard Deviation 5.71
|
-3.70 mmHg
Standard Deviation 5.89
|
-1.45 mmHg
Standard Deviation 4.79
|
-4.63 mmHg
Standard Deviation 4.92
|
-4.84 mmHg
Standard Deviation 6.78
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrsPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=10 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=10 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
7 hrs: Time Matched Baseline
|
75.70 mmHg
Standard Deviation 7.76
|
75.70 mmHg
Standard Deviation 7.76
|
75.70 mmHg
Standard Deviation 7.76
|
74.67 mmHg
Standard Deviation 7.47
|
74.67 mmHg
Standard Deviation 7.47
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
0.5 hr: Time Matched Baseline
|
87.90 mmHg
Standard Deviation 7.45
|
87.90 mmHg
Standard Deviation 7.45
|
87.90 mmHg
Standard Deviation 7.45
|
86.44 mmHg
Standard Deviation 6.21
|
86.44 mmHg
Standard Deviation 6.21
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
0.5 hr: Cycle Day 2 Change
|
-2.40 mmHg
Standard Deviation 6.04
|
-8.70 mmHg
Standard Deviation 11.37
|
-2.60 mmHg
Standard Deviation 6.50
|
-7.56 mmHg
Standard Deviation 6.48
|
-7.44 mmHg
Standard Deviation 9.81
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
1 hr: Time Matched Baseline
|
77.90 mmHg
Standard Deviation 8.58
|
77.90 mmHg
Standard Deviation 8.58
|
77.90 mmHg
Standard Deviation 8.58
|
77.11 mmHg
Standard Deviation 8.71
|
77.11 mmHg
Standard Deviation 8.71
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
1 hr: Cycle Day 2 Change
|
-2.70 mmHg
Standard Deviation 7.29
|
-10.40 mmHg
Standard Deviation 5.38
|
-6.30 mmHg
Standard Deviation 10.63
|
-7.56 mmHg
Standard Deviation 6.11
|
-11.33 mmHg
Standard Deviation 8.08
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
1.5 hrs: Time Matched Baselline
|
73.70 mmHg
Standard Deviation 11.02
|
73.70 mmHg
Standard Deviation 11.02
|
73.70 mmHg
Standard Deviation 11.02
|
72.89 mmHg
Standard Deviation 11.36
|
72.89 mmHg
Standard Deviation 11.36
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
1.5 hrs: Cycle Day 2 Change
|
-4.70 mmHg
Standard Deviation 11.54
|
-6.30 mmHg
Standard Deviation 17.63
|
-9.20 mmHg
Standard Deviation 10.61
|
-9.78 mmHg
Standard Deviation 12.36
|
-10.11 mmHg
Standard Deviation 10.76
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
2 hrs: Time Matched Baseline
|
72.30 mmHg
Standard Deviation 7.59
|
72.30 mmHg
Standard Deviation 7.59
|
72.30 mmHg
Standard Deviation 7.59
|
71.00 mmHg
Standard Deviation 6.76
|
71.00 mmHg
Standard Deviation 6.76
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
2 hrs: Cycle Day 2 Change
|
-3.10 mmHg
Standard Deviation 8.54
|
-5.60 mmHg
Standard Deviation 10.41
|
-7.40 mmHg
Standard Deviation 8.37
|
-5.33 mmHg
Standard Deviation 10.99
|
-7.89 mmHg
Standard Deviation 9.40
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
2.5 hrs: Time Matched Baseline
|
72.20 mmHg
Standard Deviation 7.93
|
72.20 mmHg
Standard Deviation 7.93
|
72.20 mmHg
Standard Deviation 7.93
|
71.89 mmHg
Standard Deviation 8.34
|
71.89 mmHg
Standard Deviation 8.34
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
2.5 hrs: Cycle Day 2 Change
|
-3.10 mmHg
Standard Deviation 12.91
|
-9.70 mmHg
Standard Deviation 14.30
|
-5.80 mmHg
Standard Deviation 11.59
|
-11.11 mmHg
Standard Deviation 8.91
|
-6.22 mmHg
Standard Deviation 9.90
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
3 hrs: Time Matched Baseline
|
73.50 mmHg
Standard Deviation 11.83
|
73.50 mmHg
Standard Deviation 11.83
|
73.50 mmHg
Standard Deviation 11.83
|
73.44 mmHg
Standard Deviation 12.55
|
73.44 mmHg
Standard Deviation 12.55
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
3 hrs: Cycle Day 2 Change
|
-5.00 mmHg
Standard Deviation 9.82
|
-7.90 mmHg
Standard Deviation 15.67
|
-8.50 mmHg
Standard Deviation 14.18
|
-8.44 mmHg
Standard Deviation 9.62
|
-7.78 mmHg
Standard Deviation 17.50
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
3.5 hrs: Time Matched Baseline
|
70.33 mmHg
Standard Deviation 9.70
|
70.33 mmHg
Standard Deviation 9.70
|
70.33 mmHg
Standard Deviation 9.70
|
69.50 mmHg
Standard Deviation 10.01
|
69.50 mmHg
Standard Deviation 10.01
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
3.5 hrs: Cycle Day 2 Change
|
-1.67 mmHg
Standard Deviation 12.57
|
-6.89 mmHg
Standard Deviation 11.04
|
-3.78 mmHg
Standard Deviation 9.19
|
-8.00 mmHg
Standard Deviation 11.83
|
-5.88 mmHg
Standard Deviation 13.89
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
4 hrs: Time Matched Baseline
|
76.60 mmHg
Standard Deviation 6.02
|
76.60 mmHg
Standard Deviation 6.02
|
76.33 mmHg
Standard Deviation 6.32
|
76.89 mmHg
Standard Deviation 6.31
|
76.89 mmHg
Standard Deviation 6.31
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
4 hrs: Cycle Day 2 Change
|
-1.90 mmHg
Standard Deviation 6.40
|
-6.10 mmHg
Standard Deviation 6.08
|
-2.22 mmHg
Standard Deviation 11.02
|
-6.56 mmHg
Standard Deviation 9.58
|
-9.67 mmHg
Standard Deviation 9.71
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
4.5 hrs: Time Matched Baseline
|
79.40 mmHg
Standard Deviation 12.88
|
79.40 mmHg
Standard Deviation 12.88
|
79.40 mmHg
Standard Deviation 12.88
|
76.56 mmHg
Standard Deviation 9.77
|
76.56 mmHg
Standard Deviation 9.77
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
4.5 hrs: Cycle Day 2 Change
|
-1.60 mmHg
Standard Deviation 11.72
|
-5.80 mmHg
Standard Deviation 11.11
|
-7.30 mmHg
Standard Deviation 9.78
|
-3.78 mmHg
Standard Deviation 7.29
|
-6.44 mmHg
Standard Deviation 7.84
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
5 hrs: Time Matched Baseline
|
70.10 mmHg
Standard Deviation 14.10
|
70.10 mmHg
Standard Deviation 14.10
|
70.10 mmHg
Standard Deviation 14.10
|
67.78 mmHg
Standard Deviation 12.76
|
67.78 mmHg
Standard Deviation 12.76
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
5 hrs: Cycle Day 2 Change
|
-1.20 mmHg
Standard Deviation 14.65
|
1.70 mmHg
Standard Deviation 14.24
|
-0.70 mmHg
Standard Deviation 13.49
|
0.11 mmHg
Standard Deviation 14.17
|
-0.67 mmHg
Standard Deviation 14.49
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
5.5 hrs: Time Matched Baseline
|
75.30 mmHg
Standard Deviation 7.54
|
75.30 mmHg
Standard Deviation 7.54
|
75.30 mmHg
Standard Deviation 7.54
|
74.22 mmHg
Standard Deviation 7.14
|
74.22 mmHg
Standard Deviation 7.14
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
5.5 hrs: Cycle Day 2 Change
|
-3.30 mmHg
Standard Deviation 9.19
|
-6.00 mmHg
Standard Deviation 8.88
|
-5.00 mmHg
Standard Deviation 7.62
|
-14.67 mmHg
Standard Deviation 10.85
|
-9.33 mmHg
Standard Deviation 9.63
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
6 hrs: Time Matched Baseline
|
74.80 mmHg
Standard Deviation 7.67
|
75.89 mmHg
Standard Deviation 7.27
|
74.80 mmHg
Standard Deviation 7.67
|
73.44 mmHg
Standard Deviation 6.75
|
73.44 mmHg
Standard Deviation 6.75
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
6 hrs: Cycle Day 2 Change
|
-5.70 mmHg
Standard Deviation 16.38
|
-7.44 mmHg
Standard Deviation 9.86
|
-6.10 mmHg
Standard Deviation 10.87
|
-15.22 mmHg
Standard Deviation 10.72
|
-8.11 mmHg
Standard Deviation 10.45
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
6.5 hrs: Time Matched Baseline
|
73.60 mmHg
Standard Deviation 7.17
|
73.60 mmHg
Standard Deviation 7.17
|
73.60 mmHg
Standard Deviation 7.17
|
72.67 mmHg
Standard Deviation 6.93
|
72.67 mmHg
Standard Deviation 6.93
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
6.5 hrs: Cycle Day 2 Change
|
-3.70 mmHg
Standard Deviation 12.28
|
-5.30 mmHg
Standard Deviation 6.86
|
-3.20 mmHg
Standard Deviation 14.86
|
-8.00 mmHg
Standard Deviation 10.81
|
-8.78 mmHg
Standard Deviation 12.34
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
7 hrs: Cycle Day 2 Change
|
-1.50 mmHg
Standard Deviation 10.56
|
-5.60 mmHg
Standard Deviation 10.39
|
-1.70 mmHg
Standard Deviation 12.46
|
-11.22 mmHg
Standard Deviation 10.11
|
-4.78 mmHg
Standard Deviation 11.98
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
7.5 hrs: Time Matched Baseline
|
73.70 mmHg
Standard Deviation 12.29
|
73.70 mmHg
Standard Deviation 12.29
|
73.70 mmHg
Standard Deviation 12.29
|
71.89 mmHg
Standard Deviation 11.54
|
71.89 mmHg
Standard Deviation 11.54
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
7.5 hrs: Cycle Day 2 Change
|
-0.80 mmHg
Standard Deviation 12.65
|
-3.50 mmHg
Standard Deviation 14.73
|
-3.20 mmHg
Standard Deviation 16.51
|
-2.78 mmHg
Standard Deviation 15.71
|
-4.11 mmHg
Standard Deviation 20.57
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
8 hrs: Time Matched Baseline
|
73.70 mmHg
Standard Deviation 13.28
|
73.70 mmHg
Standard Deviation 13.28
|
73.70 mmHg
Standard Deviation 13.28
|
71.78 mmHg
Standard Deviation 12.52
|
71.78 mmHg
Standard Deviation 12.52
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
8 hrs: Cycle Day 2 Change
|
-0.40 mmHg
Standard Deviation 15.46
|
-1.80 mmHg
Standard Deviation 12.93
|
-0.70 mmHg
Standard Deviation 13.56
|
-5.33 mmHg
Standard Deviation 17.05
|
-5.11 mmHg
Standard Deviation 18.45
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
8.5 hrs: Time Matched Baseline
|
73.70 mmHg
Standard Deviation 9.26
|
73.70 mmHg
Standard Deviation 9.26
|
73.33 mmHg
Standard Deviation 9.75
|
71.33 mmHg
Standard Deviation 5.79
|
71.33 mmHg
Standard Deviation 5.79
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
8.5 hrs: Cycle Day 2 Change
|
2.20 mmHg
Standard Deviation 9.85
|
-3.60 mmHg
Standard Deviation 7.60
|
0.89 mmHg
Standard Deviation 10.48
|
-2.67 mmHg
Standard Deviation 10.23
|
-2.78 mmHg
Standard Deviation 11.22
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
9 hrs: Time Matched Baseline
|
75.90 mmHg
Standard Deviation 10.34
|
75.90 mmHg
Standard Deviation 10.34
|
75.90 mmHg
Standard Deviation 10.34
|
74.22 mmHg
Standard Deviation 9.42
|
74.22 mmHg
Standard Deviation 9.42
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
9 hrs: Cycle Day 2 Change
|
3.80 mmHg
Standard Deviation 11.51
|
-0.90 mmHg
Standard Deviation 13.92
|
-0.80 mmHg
Standard Deviation 12.86
|
-6.67 mmHg
Standard Deviation 12.74
|
-6.67 mmHg
Standard Deviation 12.13
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
9.5 hrs: Time Matched Baseline
|
80.90 mmHg
Standard Deviation 10.28
|
80.90 mmHg
Standard Deviation 10.28
|
80.90 mmHg
Standard Deviation 10.28
|
80.00 mmHg
Standard Deviation 10.48
|
80.00 mmHg
Standard Deviation 10.48
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
9.5 hrs: Cycle Day 2 Change
|
0.60 mmHg
Standard Deviation 13.48
|
-12.20 mmHg
Standard Deviation 11.63
|
-3.60 mmHg
Standard Deviation 15.04
|
-9.78 mmHg
Standard Deviation 11.38
|
-7.11 mmHg
Standard Deviation 13.36
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
10 hrs: Time Matched Baseline
|
79.56 mmHg
Standard Deviation 7.32
|
79.56 mmHg
Standard Deviation 7.32
|
79.56 mmHg
Standard Deviation 7.32
|
78.63 mmHg
Standard Deviation 7.23
|
78.63 mmHg
Standard Deviation 7.23
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
10 hrs: Cycle Day 2 Change
|
0.56 mmHg
Standard Deviation 10.45
|
-3.67 mmHg
Standard Deviation 9.68
|
-1.78 mmHg
Standard Deviation 4.66
|
-7.75 mmHg
Standard Deviation 13.04
|
-3.75 mmHg
Standard Deviation 12.69
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
10.5 hrs: Time Matched Baseline
|
83.60 mmHg
Standard Deviation 10.24
|
84.22 mmHg
Standard Deviation 10.66
|
83.60 mmHg
Standard Deviation 10.24
|
82.56 mmHg
Standard Deviation 10.28
|
82.56 mmHg
Standard Deviation 10.28
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
10.5 hrs: Cycle Day 2 Change
|
-2.80 mmHg
Standard Deviation 9.38
|
-4.56 mmHg
Standard Deviation 9.15
|
-1.60 mmHg
Standard Deviation 4.88
|
-8.11 mmHg
Standard Deviation 11.24
|
-9.22 mmHg
Standard Deviation 10.10
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
11 hrs: Time Matched Baseline
|
76.22 mmHg
Standard Deviation 8.45
|
77.00 mmHg
Standard Deviation 8.34
|
76.22 mmHg
Standard Deviation 8.45
|
75.89 mmHg
Standard Deviation 8.02
|
75.89 mmHg
Standard Deviation 8.02
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
11 hrs: Cycle Day 2 Change
|
0.89 mmHg
Standard Deviation 10.56
|
-5.40 mmHg
Standard Deviation 7.85
|
-5.56 mmHg
Standard Deviation 8.00
|
-6.44 mmHg
Standard Deviation 9.94
|
-8.22 mmHg
Standard Deviation 12.08
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
11.5 hrs: Time Matched Baseline
|
73.50 mmHg
Standard Deviation 9.96
|
73.50 mmHg
Standard Deviation 9.96
|
73.50 mmHg
Standard Deviation 9.96
|
72.78 mmHg
Standard Deviation 10.28
|
72.78 mmHg
Standard Deviation 10.28
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
11.5 hrs: Cycle Day 2 Change
|
0.20 mmHg
Standard Deviation 9.50
|
-0.50 mmHg
Standard Deviation 11.65
|
-2.80 mmHg
Standard Deviation 8.07
|
0.78 mmHg
Standard Deviation 10.37
|
-2.78 mmHg
Standard Deviation 10.29
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
12 hrs: Time Matched Baseline
|
73.20 mmHg
Standard Deviation 6.44
|
73.20 mmHg
Standard Deviation 6.44
|
73.20 mmHg
Standard Deviation 6.44
|
71.56 mmHg
Standard Deviation 4.03
|
71.56 mmHg
Standard Deviation 4.03
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
12 hrs: Cycle Day 2 Change
|
5.30 mmHg
Standard Deviation 8.21
|
-0.10 mmHg
Standard Deviation 5.57
|
2.50 mmHg
Standard Deviation 12.06
|
1.89 mmHg
Standard Deviation 9.49
|
0.89 mmHg
Standard Deviation 8.37
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 2Population: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.
Outcome measures
| Measure |
Control
n=10 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=10 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Diastolic Blood Pressure
Time-Matched Baseline
|
75.71 mmHg
Standard Deviation 6.27
|
75.71 mmHg
Standard Deviation 6.27
|
75.71 mmHg
Standard Deviation 6.27
|
74.51 mmHg
Standard Deviation 5.28
|
74.51 mmHg
Standard Deviation 5.28
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Diastolic Blood Pressure
Cycle Day 2 Change
|
-1.26 mmHg
Standard Deviation 4.08
|
-5.10 mmHg
Standard Deviation 4.67
|
-3.59 mmHg
Standard Deviation 5.72
|
-6.71 mmHg
Standard Deviation 4.38
|
-6.34 mmHg
Standard Deviation 5.84
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrsPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=10 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=10 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure
0-4 hrs: Time Matched Baseline
|
92.61 mmHg
Standard Deviation 6.23
|
92.61 mmHg
Standard Deviation 6.23
|
92.61 mmHg
Standard Deviation 6.23
|
92.21 mmHg
Standard Deviation 6.47
|
92.21 mmHg
Standard Deviation 6.47
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure
0-4 hrs: Cycle Day 2 Change
|
-3.93 mmHg
Standard Deviation 3.38
|
-8.93 mmHg
Standard Deviation 6.29
|
-7.64 mmHg
Standard Deviation 6.16
|
-9.13 mmHg
Standard Deviation 6.21
|
-9.67 mmHg
Standard Deviation 8.37
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure
4-8 hrs: Time Matched Baseline
|
91.38 mmHg
Standard Deviation 6.49
|
91.38 mmHg
Standard Deviation 6.49
|
91.38 mmHg
Standard Deviation 6.49
|
89.99 mmHg
Standard Deviation 5.06
|
89.99 mmHg
Standard Deviation 5.06
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure
4-8 hrs: Cycle Day 2 Change
|
-3.50 mmHg
Standard Deviation 7.59
|
-5.80 mmHg
Standard Deviation 6.58
|
-5.55 mmHg
Standard Deviation 9.34
|
-10.29 mmHg
Standard Deviation 6.73
|
-8.65 mmHg
Standard Deviation 6.93
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure
8-12 hrs: Time Matched Baseline
|
93.99 mmHg
Standard Deviation 6.38
|
93.99 mmHg
Standard Deviation 6.38
|
93.99 mmHg
Standard Deviation 6.38
|
92.51 mmHg
Standard Deviation 4.63
|
92.51 mmHg
Standard Deviation 4.63
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure
8-12 hrs: Cycle Day 2 Change
|
0.36 mmHg
Standard Deviation 8.87
|
-4.34 mmHg
Standard Deviation 7.72
|
-3.00 mmHg
Standard Deviation 6.44
|
-6.81 mmHg
Standard Deviation 5.80
|
-6.58 mmHg
Standard Deviation 8.05
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrsPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=10 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=10 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
1.5 hrs: Time Matched Baseline
|
91.30 mmHg
Standard Deviation 13.02
|
91.30 mmHg
Standard Deviation 13.02
|
91.30 mmHg
Standard Deviation 13.02
|
91.22 mmHg
Standard Deviation 13.81
|
91.22 mmHg
Standard Deviation 13.81
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
1.5 hrs: Cycle Day 2 Change
|
-5.20 mmHg
Standard Deviation 11.39
|
-8.80 mmHg
Standard Deviation 17.82
|
-10.00 mmHg
Standard Deviation 11.55
|
-11.67 mmHg
Standard Deviation 14.97
|
-12.00 mmHg
Standard Deviation 15.28
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
2 hrs: Time Matched Baseline
|
89.20 mmHg
Standard Deviation 6.58
|
89.20 mmHg
Standard Deviation 6.58
|
89.20 mmHg
Standard Deviation 6.58
|
88.44 mmHg
Standard Deviation 6.50
|
88.44 mmHg
Standard Deviation 6.50
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
2 hrs: Cycle Day 2 Change
|
-1.70 mmHg
Standard Deviation 11.16
|
-6.10 mmHg
Standard Deviation 8.92
|
-9.10 mmHg
Standard Deviation 8.52
|
-8.11 mmHg
Standard Deviation 10.17
|
-8.67 mmHg
Standard Deviation 16.51
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
2.5 hrs: Time Matched Baseline
|
88.80 mmHg
Standard Deviation 6.70
|
88.80 mmHg
Standard Deviation 6.70
|
88.80 mmHg
Standard Deviation 6.70
|
88.67 mmHg
Standard Deviation 7.09
|
88.67 mmHg
Standard Deviation 7.09
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
0.5 hr: Time Matched Baseline
|
104.50 mmHg
Standard Deviation 9.96
|
104.50 mmHg
Standard Deviation 9.96
|
104.50 mmHg
Standard Deviation 9.96
|
102.00 mmHg
Standard Deviation 6.42
|
102.00 mmHg
Standard Deviation 6.42
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
0.5 hr: Cycle Day 2 Change
|
-3.70 mmHg
Standard Deviation 7.21
|
-9.20 mmHg
Standard Deviation 10.99
|
-3.90 mmHg
Standard Deviation 8.50
|
-5.33 mmHg
Standard Deviation 6.06
|
-4.11 mmHg
Standard Deviation 10.41
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
1 hr: Time Matched Baseline
|
96.80 mmHg
Standard Deviation 7.73
|
96.80 mmHg
Standard Deviation 7.73
|
96.80 mmHg
Standard Deviation 7.73
|
96.33 mmHg
Standard Deviation 8.05
|
96.33 mmHg
Standard Deviation 8.05
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
1 hr: Cycle Day 2 Change
|
-7.00 mmHg
Standard Deviation 7.73
|
-12.70 mmHg
Standard Deviation 6.80
|
-10.60 mmHg
Standard Deviation 11.05
|
-10.11 mmHg
Standard Deviation 9.24
|
-14.89 mmHg
Standard Deviation 9.31
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
2.5 hrs: Cycle Day 2 Change
|
-2.40 mmHg
Standard Deviation 12.75
|
-11.40 mmHg
Standard Deviation 15.25
|
-7.20 mmHg
Standard Deviation 10.94
|
-12.22 mmHg
Standard Deviation 9.86
|
-10.11 mmHg
Standard Deviation 9.83
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
3 hrs: Time Matched Baseline
|
88.10 mmHg
Standard Deviation 11.24
|
88.10 mmHg
Standard Deviation 11.24
|
88.10 mmHg
Standard Deviation 11.24
|
88.22 mmHg
Standard Deviation 11.91
|
88.22 mmHg
Standard Deviation 11.91
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
3 hrs: Cycle Day 2 Change
|
-4.20 mmHg
Standard Deviation 10.54
|
-6.90 mmHg
Standard Deviation 14.26
|
-5.50 mmHg
Standard Deviation 15.17
|
-8.78 mmHg
Standard Deviation 9.43
|
-7.44 mmHg
Standard Deviation 17.26
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
3.5 hrs: Time Matched Baseline
|
87.44 mmHg
Standard Deviation 10.08
|
87.44 mmHg
Standard Deviation 10.08
|
87.44 mmHg
Standard Deviation 10.08
|
87.25 mmHg
Standard Deviation 10.75
|
87.25 mmHg
Standard Deviation 10.75
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
3.5 hrs: Cycle Day 2 Change
|
-3.89 mmHg
Standard Deviation 13.40
|
-9.00 mmHg
Standard Deviation 11.24
|
-6.56 mmHg
Standard Deviation 8.80
|
-8.63 mmHg
Standard Deviation 13.16
|
-7.50 mmHg
Standard Deviation 15.68
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
4 hrs: Time Matched Baseline
|
94.10 mmHg
Standard Deviation 7.34
|
94.10 mmHg
Standard Deviation 7.34
|
92.78 mmHg
Standard Deviation 6.40
|
94.78 mmHg
Standard Deviation 7.45
|
94.78 mmHg
Standard Deviation 7.45
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
4 hrs: Cycle Day 2 Change
|
-4.00 mmHg
Standard Deviation 8.46
|
-7.90 mmHg
Standard Deviation 7.29
|
-5.78 mmHg
Standard Deviation 10.33
|
-8.78 mmHg
Standard Deviation 9.02
|
-12.11 mmHg
Standard Deviation 13.60
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
4.5 hrs: Time Matched Baseline
|
97.30 mmHg
Standard Deviation 10.92
|
97.30 mmHg
Standard Deviation 10.92
|
97.30 mmHg
Standard Deviation 10.92
|
94.67 mmHg
Standard Deviation 7.50
|
94.67 mmHg
Standard Deviation 7.50
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
4.5 hrs: Cycle Day 2 Change
|
-4.30 mmHg
Standard Deviation 7.75
|
-7.40 mmHg
Standard Deviation 10.16
|
-11.30 mmHg
Standard Deviation 8.14
|
-5.89 mmHg
Standard Deviation 2.93
|
-9.67 mmHg
Standard Deviation 7.94
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
5 hrs: Time Matched Baseline
|
86.60 mmHg
Standard Deviation 12.47
|
86.60 mmHg
Standard Deviation 12.47
|
86.60 mmHg
Standard Deviation 12.47
|
84.56 mmHg
Standard Deviation 11.30
|
84.56 mmHg
Standard Deviation 11.30
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
5 hrs: Cycle Day 2 Change
|
-1.30 mmHg
Standard Deviation 14.03
|
-0.80 mmHg
Standard Deviation 11.52
|
-2.80 mmHg
Standard Deviation 15.51
|
-3.00 mmHg
Standard Deviation 12.61
|
-5.11 mmHg
Standard Deviation 12.29
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
5.5 hrs: Time Matched Baseline
|
92.00 mmHg
Standard Deviation 7.21
|
92.00 mmHg
Standard Deviation 7.21
|
92.00 mmHg
Standard Deviation 7.21
|
91.11 mmHg
Standard Deviation 7.04
|
91.11 mmHg
Standard Deviation 7.04
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
5.5 hrs: Cycle Day 2 Change
|
-3.40 mmHg
Standard Deviation 10.95
|
-8.70 mmHg
Standard Deviation 8.38
|
-7.10 mmHg
Standard Deviation 8.12
|
-18.44 mmHg
Standard Deviation 10.03
|
-13.33 mmHg
Standard Deviation 11.09
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
6 hrs: Time Matched Baseline
|
90.70 mmHg
Standard Deviation 7.18
|
92.33 mmHg
Standard Deviation 5.29
|
90.70 mmHg
Standard Deviation 7.18
|
89.78 mmHg
Standard Deviation 6.96
|
89.78 mmHg
Standard Deviation 6.96
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
6 hrs: Cycle Day 2 Change
|
-5.80 mmHg
Standard Deviation 14.99
|
-9.00 mmHg
Standard Deviation 9.54
|
-7.20 mmHg
Standard Deviation 11.06
|
-15.56 mmHg
Standard Deviation 10.50
|
-10.67 mmHg
Standard Deviation 11.15
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
6.5 hrs: Time Matched Baseline
|
89.80 mmHg
Standard Deviation 6.41
|
89.80 mmHg
Standard Deviation 6.41
|
89.80 mmHg
Standard Deviation 6.41
|
89.44 mmHg
Standard Deviation 6.69
|
89.44 mmHg
Standard Deviation 6.69
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
6.5 hrs: Cycle Day 2 Change
|
-3.50 mmHg
Standard Deviation 12.09
|
-6.10 mmHg
Standard Deviation 9.18
|
-4.40 mmHg
Standard Deviation 12.82
|
-11.44 mmHg
Standard Deviation 11.07
|
-11.33 mmHg
Standard Deviation 10.63
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
7 hrs: Time Matched Baseline
|
92.90 mmHg
Standard Deviation 7.92
|
92.90 mmHg
Standard Deviation 7.92
|
92.90 mmHg
Standard Deviation 7.92
|
92.44 mmHg
Standard Deviation 8.26
|
92.44 mmHg
Standard Deviation 8.26
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
7 hrs: Cycle Day 2 Change
|
-3.90 mmHg
Standard Deviation 12.06
|
-8.50 mmHg
Standard Deviation 12.43
|
-5.60 mmHg
Standard Deviation 12.73
|
-14.11 mmHg
Standard Deviation 10.81
|
-6.44 mmHg
Standard Deviation 11.67
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
7.5 hrs: Time Matched Baseline
|
90.50 mmHg
Standard Deviation 11.72
|
90.50 mmHg
Standard Deviation 11.72
|
90.50 mmHg
Standard Deviation 11.72
|
88.78 mmHg
Standard Deviation 11.01
|
88.78 mmHg
Standard Deviation 11.01
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
7.5 hrs: Cycle Day 2 Change
|
-2.70 mmHg
Standard Deviation 15.60
|
-3.90 mmHg
Standard Deviation 15.15
|
-3.70 mmHg
Standard Deviation 17.84
|
-6.33 mmHg
Standard Deviation 16.67
|
-5.44 mmHg
Standard Deviation 18.26
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
8 hrs: Time Matched Baseline
|
91.20 mmHg
Standard Deviation 13.00
|
91.20 mmHg
Standard Deviation 13.00
|
91.20 mmHg
Standard Deviation 13.00
|
89.11 mmHg
Standard Deviation 11.88
|
89.11 mmHg
Standard Deviation 11.88
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
8 hrs: Cycle Day 2 Change
|
-3.10 mmHg
Standard Deviation 17.12
|
-3.90 mmHg
Standard Deviation 12.57
|
-2.30 mmHg
Standard Deviation 15.82
|
-7.56 mmHg
Standard Deviation 17.98
|
-7.22 mmHg
Standard Deviation 13.63
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
8.5 hrs: Time Matched Baseline
|
91.80 mmHg
Standard Deviation 10.08
|
91.80 mmHg
Standard Deviation 10.08
|
91.00 mmHg
Standard Deviation 10.34
|
89.44 mmHg
Standard Deviation 7.20
|
89.44 mmHg
Standard Deviation 7.20
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
8.5 hrs: Cycle Day 2 Change
|
-0.80 mmHg
Standard Deviation 11.21
|
-6.30 mmHg
Standard Deviation 9.26
|
-0.89 mmHg
Standard Deviation 10.29
|
-6.11 mmHg
Standard Deviation 12.73
|
-6.33 mmHg
Standard Deviation 11.28
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
9 hrs: Time Matched Baseline
|
92.00 mmHg
Standard Deviation 8.50
|
92.00 mmHg
Standard Deviation 8.50
|
92.00 mmHg
Standard Deviation 8.50
|
90.44 mmHg
Standard Deviation 7.35
|
90.44 mmHg
Standard Deviation 7.35
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
9 hrs: Cycle Day 2 Change
|
3.30 mmHg
Standard Deviation 12.00
|
-1.80 mmHg
Standard Deviation 14.61
|
-1.30 mmHg
Standard Deviation 14.25
|
-7.44 mmHg
Standard Deviation 12.41
|
-8.11 mmHg
Standard Deviation 11.26
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
9.5 hrs: Time Matched Baseline
|
96.40 mmHg
Standard Deviation 11.75
|
96.40 mmHg
Standard Deviation 11.75
|
96.40 mmHg
Standard Deviation 11.75
|
95.22 mmHg
Standard Deviation 11.82
|
95.22 mmHg
Standard Deviation 11.82
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
9.5 hrs: Cycle Day 2 Change
|
1.50 mmHg
Standard Deviation 20.74
|
-11.90 mmHg
Standard Deviation 14.81
|
-3.40 mmHg
Standard Deviation 16.81
|
-11.11 mmHg
Standard Deviation 15.32
|
-8.22 mmHg
Standard Deviation 16.05
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
10 hrs: Time Matched Baseline
|
95.11 mmHg
Standard Deviation 9.68
|
95.11 mmHg
Standard Deviation 9.68
|
95.11 mmHg
Standard Deviation 9.68
|
93.63 mmHg
Standard Deviation 9.18
|
93.63 mmHg
Standard Deviation 9.18
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
10 hrs: Cycle Day 2 Change
|
-0.44 mmHg
Standard Deviation 14.79
|
-4.89 mmHg
Standard Deviation 10.73
|
-2.56 mmHg
Standard Deviation 7.99
|
-9.75 mmHg
Standard Deviation 14.32
|
-2.50 mmHg
Standard Deviation 18.24
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
10.5 hrs: Time Matched Baseline
|
101.00 mmHg
Standard Deviation 10.84
|
101.78 mmHg
Standard Deviation 11.20
|
101.00 mmHg
Standard Deviation 10.84
|
98.89 mmHg
Standard Deviation 9.06
|
98.89 mmHg
Standard Deviation 9.06
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
10.5 hrs: Cycle Day 2 Change
|
-2.70 mmHg
Standard Deviation 13.15
|
-3.67 mmHg
Standard Deviation 10.95
|
-3.50 mmHg
Standard Deviation 6.52
|
-10.11 mmHg
Standard Deviation 7.69
|
-10.67 mmHg
Standard Deviation 11.45
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
11 hrs: Time Matched Baseline
|
95.00 mmHg
Standard Deviation 10.28
|
95.50 mmHg
Standard Deviation 9.82
|
95.00 mmHg
Standard Deviation 10.28
|
94.33 mmHg
Standard Deviation 9.66
|
94.33 mmHg
Standard Deviation 9.66
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
11 hrs: Cycle Day 2 Change
|
-0.56 mmHg
Standard Deviation 11.17
|
-7.10 mmHg
Standard Deviation 11.26
|
-8.22 mmHg
Standard Deviation 9.92
|
-10.00 mmHg
Standard Deviation 14.24
|
-11.78 mmHg
Standard Deviation 14.70
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
11.5 hrs: Time Matched Baseline
|
90.10 mmHg
Standard Deviation 8.45
|
90.10 mmHg
Standard Deviation 8.45
|
90.10 mmHg
Standard Deviation 8.45
|
89.56 mmHg
Standard Deviation 8.78
|
89.56 mmHg
Standard Deviation 8.78
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
11.5 hrs: Cycle Day 2 Change
|
-1.40 mmHg
Standard Deviation 7.66
|
0.60 mmHg
Standard Deviation 10.62
|
-5.20 mmHg
Standard Deviation 5.39
|
-0.78 mmHg
Standard Deviation 8.35
|
-3.89 mmHg
Standard Deviation 7.46
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
12 hrs: Time Matched Baseline
|
90.45 mmHg
Standard Deviation 6.30
|
90.45 mmHg
Standard Deviation 6.30
|
90.45 mmHg
Standard Deviation 6.30
|
88.94 mmHg
Standard Deviation 4.37
|
88.94 mmHg
Standard Deviation 4.37
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
12 hrs: Cycle Day 2 Change
|
3.80 mmHg
Standard Deviation 7.63
|
-0.25 mmHg
Standard Deviation 7.67
|
0.95 mmHg
Standard Deviation 10.96
|
-0.72 mmHg
Standard Deviation 6.64
|
-0.89 mmHg
Standard Deviation 7.88
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 2Population: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.
Outcome measures
| Measure |
Control
n=10 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=10 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Mean Arterial Pressure
Time-Matched Baseline
|
92.64 mmHg
Standard Deviation 5.77
|
92.64 mmHg
Standard Deviation 5.77
|
92.64 mmHg
Standard Deviation 5.77
|
91.55 mmHg
Standard Deviation 4.90
|
91.55 mmHg
Standard Deviation 4.90
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Mean Arterial Pressure
Cycle Day 2 Change
|
-2.33 mmHg
Standard Deviation 5.21
|
-6.33 mmHg
Standard Deviation 5.44
|
-5.34 mmHg
Standard Deviation 6.58
|
-8.72 mmHg
Standard Deviation 5.43
|
-8.28 mmHg
Standard Deviation 6.54
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrsPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=10 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=10 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse
0-4 hrs: Time Matched Baseline
|
75.61 mmHg
Standard Deviation 12.37
|
75.61 mmHg
Standard Deviation 12.37
|
75.61 mmHg
Standard Deviation 12.37
|
76.59 mmHg
Standard Deviation 12.70
|
76.59 mmHg
Standard Deviation 12.70
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse
0-4 hrs: Cycle Day 2 Change
|
2.49 mmHg
Standard Deviation 3.62
|
6.11 mmHg
Standard Deviation 4.49
|
8.91 mmHg
Standard Deviation 7.60
|
7.10 mmHg
Standard Deviation 4.43
|
7.38 mmHg
Standard Deviation 6.58
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse
4-8 hrs: Time Matched Baseline
|
73.24 mmHg
Standard Deviation 11.19
|
73.24 mmHg
Standard Deviation 11.19
|
73.24 mmHg
Standard Deviation 11.19
|
73.81 mmHg
Standard Deviation 11.72
|
73.81 mmHg
Standard Deviation 11.72
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse
4-8 hrs: Cycle Day 2 Change
|
9.24 mmHg
Standard Deviation 5.30
|
7.56 mmHg
Standard Deviation 6.51
|
6.50 mmHg
Standard Deviation 7.82
|
12.82 mmHg
Standard Deviation 7.16
|
8.89 mmHg
Standard Deviation 8.83
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse
8-12 hrs: Time Matched Baseline
|
76.22 mmHg
Standard Deviation 12.59
|
76.22 mmHg
Standard Deviation 12.59
|
76.22 mmHg
Standard Deviation 12.59
|
76.95 mmHg
Standard Deviation 13.13
|
76.95 mmHg
Standard Deviation 13.13
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse
8-12 hrs: Cycle Day 2 Change
|
1.91 mmHg
Standard Deviation 7.04
|
-1.20 mmHg
Standard Deviation 6.52
|
1.51 mmHg
Standard Deviation 5.34
|
2.53 mmHg
Standard Deviation 5.55
|
3.35 mmHg
Standard Deviation 8.48
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrsPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=10 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=10 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
1 hr: Time Matched Baseline
|
73.50 mmHg
Standard Deviation 11.69
|
73.50 mmHg
Standard Deviation 11.69
|
73.50 mmHg
Standard Deviation 11.69
|
74.44 mmHg
Standard Deviation 11.99
|
74.44 mmHg
Standard Deviation 11.99
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
5 hrs: Time Matched Baseline
|
75.50 mmHg
Standard Deviation 10.21
|
75.50 mmHg
Standard Deviation 10.21
|
75.50 mmHg
Standard Deviation 10.21
|
76.44 mmHg
Standard Deviation 10.36
|
76.44 mmHg
Standard Deviation 10.36
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
5.5 hrs: Cycle Day 2 Change
|
7.80 mmHg
Standard Deviation 11.69
|
5.70 mmHg
Standard Deviation 11.79
|
6.80 mmHg
Standard Deviation 11.12
|
10.00 mmHg
Standard Deviation 11.22
|
5.00 mmHg
Standard Deviation 13.22
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
8 hrs: Time Matched Baseline
|
71.20 mmHg
Standard Deviation 13.72
|
71.20 mmHg
Standard Deviation 13.72
|
71.20 mmHg
Standard Deviation 13.72
|
72.44 mmHg
Standard Deviation 13.94
|
72.44 mmHg
Standard Deviation 13.94
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
11 hrs: Time Matched Baseline
|
82.22 mmHg
Standard Deviation 17.10
|
81.30 mmHg
Standard Deviation 16.38
|
82.22 mmHg
Standard Deviation 17.10
|
82.56 mmHg
Standard Deviation 16.86
|
82.56 mmHg
Standard Deviation 16.86
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
0.5 hr: Time Matched Baseline
|
76.30 mmHg
Standard Deviation 9.89
|
76.30 mmHg
Standard Deviation 9.89
|
76.30 mmHg
Standard Deviation 9.89
|
75.67 mmHg
Standard Deviation 10.27
|
75.67 mmHg
Standard Deviation 10.27
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
0.5 hr: Cycle Day 2 Change
|
-0.60 mmHg
Standard Deviation 4.17
|
1.60 mmHg
Standard Deviation 5.23
|
1.50 mmHg
Standard Deviation 8.34
|
2.67 mmHg
Standard Deviation 9.62
|
2.11 mmHg
Standard Deviation 5.42
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
1 hr: Cycle Day 2 Change
|
3.00 mmHg
Standard Deviation 6.09
|
7.30 mmHg
Standard Deviation 8.19
|
11.00 mmHg
Standard Deviation 10.09
|
8.11 mmHg
Standard Deviation 7.85
|
9.89 mmHg
Standard Deviation 9.98
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
1.5 hrs: Time Matched Baseline
|
74.80 mmHg
Standard Deviation 12.25
|
74.80 mmHg
Standard Deviation 12.25
|
74.80 mmHg
Standard Deviation 12.25
|
75.56 mmHg
Standard Deviation 12.74
|
75.56 mmHg
Standard Deviation 12.74
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
1.5 hrs: Cycle Day 2 Change
|
5.60 mmHg
Standard Deviation 4.93
|
18.90 mmHg
Standard Deviation 12.72
|
14.60 mmHg
Standard Deviation 14.21
|
10.44 mmHg
Standard Deviation 7.75
|
14.44 mmHg
Standard Deviation 5.39
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
2 hrs: Time Matched Baseline
|
78.80 mmHg
Standard Deviation 15.30
|
78.80 mmHg
Standard Deviation 15.30
|
78.80 mmHg
Standard Deviation 15.30
|
80.22 mmHg
Standard Deviation 15.51
|
80.22 mmHg
Standard Deviation 15.51
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
2 hrs: Cycle Day 2 Change
|
0.90 mmHg
Standard Deviation 8.13
|
7.40 mmHg
Standard Deviation 5.91
|
6.90 mmHg
Standard Deviation 7.03
|
14.00 mmHg
Standard Deviation 22.92
|
5.33 mmHg
Standard Deviation 9.50
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
2.5 hrs: Time Matched Baseline
|
76.60 mmHg
Standard Deviation 13.43
|
76.60 mmHg
Standard Deviation 13.43
|
76.60 mmHg
Standard Deviation 13.43
|
77.89 mmHg
Standard Deviation 13.57
|
77.89 mmHg
Standard Deviation 13.57
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
2.5 hrs: Cycle Day 2 Change
|
3.20 mmHg
Standard Deviation 7.79
|
5.20 mmHg
Standard Deviation 6.71
|
9.30 mmHg
Standard Deviation 12.28
|
8.44 mmHg
Standard Deviation 7.70
|
6.67 mmHg
Standard Deviation 11.70
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
3 hrs: Time Matched Baseline
|
77.10 mmHg
Standard Deviation 15.53
|
77.10 mmHg
Standard Deviation 15.53
|
77.10 mmHg
Standard Deviation 15.53
|
78.56 mmHg
Standard Deviation 15.73
|
78.56 mmHg
Standard Deviation 15.73
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
3 hrs: Cycle Day 2 Change
|
2.70 mmHg
Standard Deviation 9.01
|
1.20 mmHg
Standard Deviation 10.81
|
12.10 mmHg
Standard Deviation 14.56
|
2.22 mmHg
Standard Deviation 8.77
|
7.89 mmHg
Standard Deviation 12.23
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
3.5 hrs: Time Matched Baseline
|
74.33 mmHg
Standard Deviation 15.84
|
74.33 mmHg
Standard Deviation 15.84
|
74.33 mmHg
Standard Deviation 15.84
|
75.75 mmHg
Standard Deviation 16.31
|
75.75 mmHg
Standard Deviation 16.31
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
3.5 hrs: Cycle Day 2 Change
|
2.78 mmHg
Standard Deviation 6.85
|
2.44 mmHg
Standard Deviation 5.17
|
8.33 mmHg
Standard Deviation 10.10
|
5.13 mmHg
Standard Deviation 10.52
|
5.13 mmHg
Standard Deviation 13.82
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
4 hrs: Time Matched Baseline
|
73.70 mmHg
Standard Deviation 15.98
|
73.70 mmHg
Standard Deviation 15.98
|
74.67 mmHg
Standard Deviation 16.64
|
75.11 mmHg
Standard Deviation 16.27
|
75.11 mmHg
Standard Deviation 16.27
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
4 hrs: Cycle Day 2 Change
|
2.70 mmHg
Standard Deviation 6.63
|
3.90 mmHg
Standard Deviation 9.45
|
8.89 mmHg
Standard Deviation 13.59
|
5.78 mmHg
Standard Deviation 8.76
|
7.44 mmHg
Standard Deviation 13.53
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
4.5 hrs: Time Matched Baseline
|
80.80 mmHg
Standard Deviation 13.73
|
80.80 mmHg
Standard Deviation 13.73
|
80.80 mmHg
Standard Deviation 13.73
|
81.56 mmHg
Standard Deviation 14.34
|
81.56 mmHg
Standard Deviation 14.34
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
4.5 hrs: Cycle Day 2 Change
|
4.70 mmHg
Standard Deviation 7.02
|
2.70 mmHg
Standard Deviation 8.03
|
9.60 mmHg
Standard Deviation 15.24
|
10.56 mmHg
Standard Deviation 10.86
|
7.33 mmHg
Standard Deviation 9.64
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
5 hrs: Cycle Day 2 Change
|
5.50 mmHg
Standard Deviation 11.45
|
7.90 mmHg
Standard Deviation 13.87
|
4.00 mmHg
Standard Deviation 10.65
|
17.78 mmHg
Standard Deviation 14.81
|
7.00 mmHg
Standard Deviation 15.26
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
5.5 hrs: Time Matched Baseline
|
75.50 mmHg
Standard Deviation 10.10
|
75.50 mmHg
Standard Deviation 10.10
|
75.50 mmHg
Standard Deviation 10.10
|
76.11 mmHg
Standard Deviation 10.52
|
76.11 mmHg
Standard Deviation 10.52
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
6 hrs: Time Matched Baseline
|
72.00 mmHg
Standard Deviation 11.11
|
71.44 mmHg
Standard Deviation 11.63
|
72.00 mmHg
Standard Deviation 11.11
|
72.22 mmHg
Standard Deviation 11.76
|
72.22 mmHg
Standard Deviation 11.76
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
6 hrs: Cycle Day 2 Change
|
12.60 mmHg
Standard Deviation 15.07
|
7.89 mmHg
Standard Deviation 9.57
|
7.40 mmHg
Standard Deviation 10.36
|
16.00 mmHg
Standard Deviation 13.87
|
8.56 mmHg
Standard Deviation 8.79
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
6.5 hrs: Time Matched Baseline
|
71.40 mmHg
Standard Deviation 11.04
|
71.40 mmHg
Standard Deviation 11.04
|
71.40 mmHg
Standard Deviation 11.04
|
71.56 mmHg
Standard Deviation 11.70
|
71.56 mmHg
Standard Deviation 11.70
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
6.5 hrs: Cycle Day 2 Change
|
13.10 mmHg
Standard Deviation 7.53
|
10.30 mmHg
Standard Deviation 10.47
|
8.30 mmHg
Standard Deviation 11.73
|
13.44 mmHg
Standard Deviation 10.57
|
13.00 mmHg
Standard Deviation 15.73
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
7 hrs: Time Matched Baseline
|
69.10 mmHg
Standard Deviation 13.47
|
69.10 mmHg
Standard Deviation 13.47
|
69.10 mmHg
Standard Deviation 13.47
|
69.56 mmHg
Standard Deviation 14.20
|
69.56 mmHg
Standard Deviation 14.20
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
7 hrs: Cycle Day 2 Change
|
14.00 mmHg
Standard Deviation 6.39
|
14.20 mmHg
Standard Deviation 14.20
|
8.30 mmHg
Standard Deviation 7.04
|
12.56 mmHg
Standard Deviation 4.42
|
13.00 mmHg
Standard Deviation 9.75
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
7.5 hrs: Time Matched Baseline
|
70.40 mmHg
Standard Deviation 14.42
|
70.40 mmHg
Standard Deviation 14.42
|
70.40 mmHg
Standard Deviation 14.42
|
70.56 mmHg
Standard Deviation 15.28
|
70.56 mmHg
Standard Deviation 15.28
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
7.5 hrs: Cycle Day 2 Change
|
9.70 mmHg
Standard Deviation 9.23
|
6.40 mmHg
Standard Deviation 8.76
|
5.70 mmHg
Standard Deviation 7.24
|
12.78 mmHg
Standard Deviation 9.76
|
11.67 mmHg
Standard Deviation 14.98
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
8 hrs: Cycle Day 2 Change
|
6.50 mmHg
Standard Deviation 7.04
|
3.70 mmHg
Standard Deviation 5.14
|
1.90 mmHg
Standard Deviation 6.57
|
9.44 mmHg
Standard Deviation 8.11
|
5.56 mmHg
Standard Deviation 8.71
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
8.5 hrs: Time Matched Baseline
|
70.40 mmHg
Standard Deviation 13.63
|
70.40 mmHg
Standard Deviation 13.63
|
71.33 mmHg
Standard Deviation 14.12
|
71.22 mmHg
Standard Deviation 14.19
|
71.22 mmHg
Standard Deviation 14.19
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
8.5 hrs: Cycle Day 2 Change
|
5.80 mmHg
Standard Deviation 9.61
|
3.60 mmHg
Standard Deviation 7.18
|
1.33 mmHg
Standard Deviation 8.44
|
6.33 mmHg
Standard Deviation 7.92
|
8.78 mmHg
Standard Deviation 10.35
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
9 hrs: Time Matched Baseline
|
71.30 mmHg
Standard Deviation 15.10
|
71.30 mmHg
Standard Deviation 15.10
|
71.30 mmHg
Standard Deviation 15.10
|
71.89 mmHg
Standard Deviation 15.89
|
71.89 mmHg
Standard Deviation 15.89
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
9 hrs: Cycle Day 2 Change
|
5.30 mmHg
Standard Deviation 12.45
|
1.50 mmHg
Standard Deviation 9.65
|
1.60 mmHg
Standard Deviation 10.27
|
2.22 mmHg
Standard Deviation 13.89
|
4.44 mmHg
Standard Deviation 11.26
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
9.5 hrs: Time Matched Baseline
|
72.00 mmHg
Standard Deviation 14.83
|
72.00 mmHg
Standard Deviation 14.83
|
72.00 mmHg
Standard Deviation 14.83
|
72.67 mmHg
Standard Deviation 15.57
|
72.67 mmHg
Standard Deviation 15.57
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
9.5 hrs: Cycle Day 2 Change
|
3.60 mmHg
Standard Deviation 9.38
|
0.80 mmHg
Standard Deviation 9.20
|
3.60 mmHg
Standard Deviation 12.33
|
6.22 mmHg
Standard Deviation 7.51
|
8.78 mmHg
Standard Deviation 10.17
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
10 hrs: Time Matched Baseline
|
73.56 mmHg
Standard Deviation 12.82
|
73.56 mmHg
Standard Deviation 12.82
|
73.56 mmHg
Standard Deviation 12.82
|
74.13 mmHg
Standard Deviation 13.58
|
74.13 mmHg
Standard Deviation 13.58
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
10 hrs: Cycle Day 2 Change
|
4.89 mmHg
Standard Deviation 12.20
|
1.56 mmHg
Standard Deviation 8.00
|
3.11 mmHg
Standard Deviation 5.88
|
7.88 mmHg
Standard Deviation 9.60
|
5.75 mmHg
Standard Deviation 12.13
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
10.5 hrs: Time Matched Baseline
|
81.00 mmHg
Standard Deviation 12.12
|
81.78 mmHg
Standard Deviation 12.59
|
81.00 mmHg
Standard Deviation 12.12
|
81.33 mmHg
Standard Deviation 12.81
|
81.33 mmHg
Standard Deviation 12.81
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
10.5 hrs: Cycle Day 2 Change
|
0.60 mmHg
Standard Deviation 10.84
|
-3.89 mmHg
Standard Deviation 10.17
|
-1.00 mmHg
Standard Deviation 5.77
|
3.11 mmHg
Standard Deviation 11.19
|
2.11 mmHg
Standard Deviation 9.51
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
11 hrs: Cycle Day 2 Change
|
-4.33 mmHg
Standard Deviation 14.96
|
-7.30 mmHg
Standard Deviation 14.62
|
-2.67 mmHg
Standard Deviation 12.47
|
-2.22 mmHg
Standard Deviation 15.21
|
-3.56 mmHg
Standard Deviation 7.49
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
11.5 hrs: Time Matched Baseline
|
81.60 mmHg
Standard Deviation 15.90
|
81.60 mmHg
Standard Deviation 15.90
|
81.60 mmHg
Standard Deviation 15.90
|
82.78 mmHg
Standard Deviation 16.40
|
82.78 mmHg
Standard Deviation 16.40
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
11.5 hrs: Cycle Day 2 Change
|
-3.10 mmHg
Standard Deviation 8.70
|
-5.80 mmHg
Standard Deviation 11.28
|
0.20 mmHg
Standard Deviation 9.44
|
-4.89 mmHg
Standard Deviation 9.52
|
-3.56 mmHg
Standard Deviation 13.42
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
12 hrs: Time Matched Baseline
|
78.45 mmHg
Standard Deviation 12.16
|
78.45 mmHg
Standard Deviation 12.16
|
78.45 mmHg
Standard Deviation 12.16
|
78.94 mmHg
Standard Deviation 12.79
|
78.94 mmHg
Standard Deviation 12.79
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
12 hrs: Cycle Day 2 Change
|
2.25 mmHg
Standard Deviation 12.76
|
0.65 mmHg
Standard Deviation 9.60
|
4.40 mmHg
Standard Deviation 7.17
|
2.44 mmHg
Standard Deviation 6.94
|
2.78 mmHg
Standard Deviation 10.60
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle); Cycle Day 2Population: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.
Outcome measures
| Measure |
Control
n=10 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=10 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Pulse
Cycle Day 2 Change
|
4.55 mmHg
Standard Deviation 4.43
|
4.14 mmHg
Standard Deviation 4.80
|
5.70 mmHg
Standard Deviation 6.22
|
7.49 mmHg
Standard Deviation 3.88
|
6.55 mmHg
Standard Deviation 7.30
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Pulse
Time-Matched Baseline
|
75.01 mmHg
Standard Deviation 11.95
|
75.01 mmHg
Standard Deviation 11.95
|
75.01 mmHg
Standard Deviation 11.95
|
75.78 mmHg
Standard Deviation 12.42
|
75.78 mmHg
Standard Deviation 12.42
|
—
|
PRIMARY outcome
Timeframe: Follow-up Visit Day 32 (± 2 days)Population: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Pulse
|
-2.5 bpm
Standard Deviation 5.4
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Follow-up Visit Day 32 (± 2 days)Population: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Systolic Blood Pressure
|
3.5 mmHg
Standard Deviation 7.3
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Follow-up Visit Day 32 (± 2 days)Population: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Diastolic Blood Pressure
|
-0.5 mmHg
Standard Deviation 3.8
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Study Baseline; Cycle Day 3: 0 h, 4 h, 12 hPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Study baseline is defined as the Day -1 assessment. Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=11 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=10 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
n=9 Participants
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Study Baseline Over Time in Endothelial Function: Reactive Hyperemia Index (RHI)
Change at Cycle Day 3, 12 h
|
-0.03 units on a scale
Standard Deviation 0.64
|
0.33 units on a scale
Standard Deviation 1.07
|
0.29 units on a scale
Standard Deviation 0.68
|
0.07 units on a scale
Standard Deviation 0.91
|
0.17 units on a scale
Standard Deviation 1.06
|
0.37 units on a scale
Standard Deviation 1.14
|
|
Change From Study Baseline Over Time in Endothelial Function: Reactive Hyperemia Index (RHI)
Study Baseline
|
2.21 units on a scale
Standard Deviation 0.62
|
2.21 units on a scale
Standard Deviation 0.62
|
2.28 units on a scale
Standard Deviation 0.61
|
2.21 units on a scale
Standard Deviation 0.66
|
2.28 units on a scale
Standard Deviation 0.66
|
2.28 units on a scale
Standard Deviation 0.66
|
|
Change From Study Baseline Over Time in Endothelial Function: Reactive Hyperemia Index (RHI)
Change at Cycle Day 3, 0 h
|
-0.08 units on a scale
Standard Deviation 0.74
|
-0.14 units on a scale
Standard Deviation 0.91
|
-0.13 units on a scale
Standard Deviation 0.69
|
0.31 units on a scale
Standard Deviation 1.08
|
0.20 units on a scale
Standard Deviation 0.87
|
-0.09 units on a scale
Standard Deviation 0.87
|
|
Change From Study Baseline Over Time in Endothelial Function: Reactive Hyperemia Index (RHI)
Change at Cycle Day 3, 4 h
|
-0.39 units on a scale
Standard Deviation 0.65
|
0.08 units on a scale
Standard Deviation 0.99
|
0.01 units on a scale
Standard Deviation 0.75
|
-0.15 units on a scale
Standard Deviation 0.80
|
-0.17 units on a scale
Standard Deviation 0.98
|
-0.06 units on a scale
Standard Deviation 0.78
|
PRIMARY outcome
Timeframe: Time-matched Baseline (Placebo Cycle); Cycle Day 3: 0 h, 4 h, 12 hPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction. Baseline is designated per protocol as Day 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 3 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI
Time-Matched Baseline, 0 h
|
2.13 units on a scale
Standard Deviation 0.57
|
2.15 units on a scale
Standard Deviation 0.60
|
2.24 units on a scale
Standard Deviation 0.49
|
2.28 units on a scale
Standard Deviation 0.50
|
2.28 units on a scale
Standard Deviation 0.50
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI
Change at Cycle Day 3, 0 h
|
-0.07 units on a scale
Standard Deviation 0.74
|
0 units on a scale
Standard Deviation 0.87
|
0.28 units on a scale
Standard Deviation 0.64
|
0.19 units on a scale
Standard Deviation 0.39
|
-0.09 units on a scale
Standard Deviation 1.01
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI
Time-Matched Baseline, 4 h
|
1.82 units on a scale
Standard Deviation 0.26
|
1.82 units on a scale
Standard Deviation 0.26
|
1.82 units on a scale
Standard Deviation 0.27
|
1.84 units on a scale
Standard Deviation 0.27
|
1.84 units on a scale
Standard Deviation 0.27
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI
Change at Cycle Day 3, 4 h
|
0.47 units on a scale
Standard Deviation 1.02
|
0.40 units on a scale
Standard Deviation 0.50
|
0.25 units on a scale
Standard Deviation 0.60
|
0.26 units on a scale
Standard Deviation 0.67
|
0.37 units on a scale
Standard Deviation 0.75
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI
Time-Matched Baseline, 12 h
|
2.18 units on a scale
Standard Deviation 0.48
|
2.18 units on a scale
Standard Deviation 0.48
|
2.16 units on a scale
Standard Deviation 0.51
|
2.12 units on a scale
Standard Deviation 0.51
|
2.12 units on a scale
Standard Deviation 0.51
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI
Change at Cycle Day 3, 12 h
|
0.36 units on a scale
Standard Deviation 0.77
|
0.32 units on a scale
Standard Deviation 0.39
|
0.20 units on a scale
Standard Deviation 0.54
|
0.32 units on a scale
Standard Deviation 0.66
|
0.53 units on a scale
Standard Deviation 0.68
|
—
|
PRIMARY outcome
Timeframe: Follow-up Visit Day 32 (± 2 days)Population: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.
Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Pre- to Post-Nitroglycerin Dose Assessment in Endothelial Function: RHI
|
-0.05 units on a scale
Standard Deviation 0.37
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Time-Matched Baseline (Placebo Cycle), Cycle Day 1, 0 h, Cycle Day 1, 4 hPopulation: PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Time-matched baseline is defined as the corresponding assessment on Day 1 of the placebo cycle. Platelet function assessment used the PFA-100® instrument to evaluate collagen/epinephrine time to aggregation. Baseline is designated per protocol as Day 1 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 of each IW-1973 dose at given time point are presented as the second row of data.
Outcome measures
| Measure |
Control
n=11 Participants
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 Participants
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=10 Participants
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=9 Participants
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 Participants
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Change From Time-Matched Baseline (Placebo Cycle) in Platelet Function Assessments: Collagen/Epinephrine Time to Aggregation
Time-Matched Baseline, 0 h
|
131.8 secs
Standard Deviation 60.6
|
132.8 secs
Standard Deviation 63.8
|
115.5 secs
Standard Deviation 28.7
|
114.8 secs
Standard Deviation 30.3
|
114.8 secs
Standard Deviation 30.3
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) in Platelet Function Assessments: Collagen/Epinephrine Time to Aggregation
Change at Cycle Day 1, 0 h
|
-21.0 secs
Standard Deviation 54.6
|
-38.7 secs
Standard Deviation 46.5
|
-6.8 secs
Standard Deviation 25.0
|
9.9 secs
Standard Deviation 47.4
|
-4.2 secs
Standard Deviation 28.8
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) in Platelet Function Assessments: Collagen/Epinephrine Time to Aggregation
Time-Matched Baseline, 4 h
|
121.3 secs
Standard Deviation 35.0
|
121.3 secs
Standard Deviation 35.0
|
115.0 secs
Standard Deviation 29.6
|
114.6 secs
Standard Deviation 31.4
|
114.6 secs
Standard Deviation 31.4
|
—
|
|
Change From Time-Matched Baseline (Placebo Cycle) in Platelet Function Assessments: Collagen/Epinephrine Time to Aggregation
Change at Cycle Day 1, 4 h
|
-3.8 secs
Standard Deviation 22.2
|
-15.5 secs
Standard Deviation 40.2
|
-7.4 secs
Standard Deviation 23.9
|
14.2 secs
Standard Deviation 42.7
|
-4.0 secs
Standard Deviation 32.4
|
—
|
Adverse Events
Control
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
10 mg IW-1973
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
20 mg IW-1973
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
30 mg IW-1973
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
40 mg IW-1973
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
50 mg IW-1973
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 |
Control
n=11 participants at risk
Placebo taken once daily Day 1-Day 3
|
10 mg IW-1973
n=11 participants at risk
10 mg IW-1973 take once daily Day 4-Day 6
|
20 mg IW-1973
n=11 participants at risk
20 mg IW-1973 taken once daily Day 7-Day 9
|
30 mg IW-1973
n=10 participants at risk
30 mg IW-1973 taken once daily Day 10-Day 12
|
40 mg IW-1973
n=9 participants at risk
40 mg IW-1973 taken once daily Day 13-Day 15
|
50 mg IW-1973
n=9 participants at risk
50 mg IW-1973 taken once daily Day 16-Day 18
|
|---|---|---|---|---|---|---|
|
Cardiac disorders
Palpitations
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
11.1%
1/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Gastrointestinal disorders
Constipation
|
9.1%
1/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
10.0%
1/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
11.1%
1/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
11.1%
1/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
9.1%
1/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
11.1%
1/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Gastrointestinal disorders
Tongue eruption
|
9.1%
1/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
11.1%
1/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Investigations
Blood pressure systolic decreased
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
9.1%
1/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
11.1%
1/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
9.1%
1/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
10.0%
1/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
11.1%
1/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
11.1%
1/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Nervous system disorders
Headache
|
9.1%
1/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
18.2%
2/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
20.0%
2/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
11.1%
1/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
22.2%
2/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
10.0%
1/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
11.1%
1/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
9.1%
1/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
10.0%
1/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
9.1%
1/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Vascular disorders
Flushing
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
10.0%
1/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/11 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/10 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
11.1%
1/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
0.00%
0/9 • From first dose of study drug through end of trial (Day 46 [±3 days])
Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee PI may publish or disclose the results of the study 24 months after final data lock provided that sponsor can review the publication prior to public release, sponsor can request removal of confidential information of sponsor (not including results of trial), and sponsor can request a publication delay in order to protect potentially patentable information. Furthermore, if a publication committee is developing an initial publication, PI is to delay disclosure until that publication is published.
- Publication restrictions are in place
Restriction type: OTHER