Trial Outcomes & Findings for Trial of IW-1973, A Stimulator of Soluble Guanylate Cyclase (sGC) in Patients With Stable Type 2 Diabetes and Hypertension (NCT NCT03091920)
NCT ID: NCT03091920
Last Updated: 2020-08-31
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
26 participants
Primary outcome timeframe
Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42
Results posted on
2020-08-31
Participant Flow
Participant milestones
| Measure |
Placebo
Placebo oral tablet taken morning (AM) and night (PM) on Days 1-14.
|
IW-1973 40 mg Twice Dily (BID)/Once Daily (QD)
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
10
|
10
|
|
Overall Study
COMPLETED
|
6
|
9
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Placebo
Placebo oral tablet taken morning (AM) and night (PM) on Days 1-14.
|
IW-1973 40 mg Twice Dily (BID)/Once Daily (QD)
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
Baseline Characteristics
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 |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
40 to < 65 years old
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Age, Customized
>= 65 years old
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Percentage of Participants With Baseline Supine BP Less Than 130/80 mmHg
|
33.3 percentage of participants
n=5 Participants
|
80.0 percentage of participants
n=7 Participants
|
60.0 percentage of participants
n=5 Participants
|
70.0 percentage of participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42Population: Pharmacodynamic (PD) Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 2 predose AM
|
5.5 mmHg
Standard Error 3.5
|
-2.9 mmHg
Standard Error 2.8
|
-0.2 mmHg
Standard Error 2.7
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 8 predose AM
|
3.7 mmHg
Standard Error 4.6
|
-8.0 mmHg
Standard Error 3.7
|
-4.7 mmHg
Standard Error 3.6
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 8 postdose AM: 1 hour
|
-2.0 mmHg
Standard Error 5.3
|
-15.4 mmHg
Standard Error 4.3
|
-12.3 mmHg
Standard Error 4.1
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 8 postdose AM: 4 hour
|
-5.2 mmHg
Standard Error 6.1
|
-15.2 mmHg
Standard Error 4.9
|
-9.8 mmHg
Standard Error 4.7
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Study Baseline (Day 1 predose AM)
|
130.2 mmHg
Standard Error 11.1
|
120.1 mmHg
Standard Error 8.9
|
128.6 mmHg
Standard Error 10.1
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 1 postdose AM: 1 hour
|
-6.8 mmHg
Standard Error 4.8
|
-7.7 mmHg
Standard Error 3.9
|
-6.2 mmHg
Standard Error 3.7
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 1 postdose AM: 4 hour
|
4.4 mmHg
Standard Error 6.0
|
-9.5 mmHg
Standard Error 4.9
|
-11.1 mmHg
Standard Error 4.6
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 1 postdose AM: 8 hour
|
0.5 mmHg
Standard Error 5.0
|
-9.4 mmHg
Standard Error 4.0
|
-2.7 mmHg
Standard Error 3.8
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 1 predose PM
|
1.8 mmHg
Standard Error 6.3
|
-6.9 mmHg
Standard Error 5.1
|
-1.7 mmHg
Standard Error 4.8
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 1 postdose PM: 1 hour
|
-0.6 mmHg
Standard Error 5.6
|
-3.9 mmHg
Standard Error 4.5
|
-5.0 mmHg
Standard Error 4.3
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 2 postdose AM: 1 hour
|
2.0 mmHg
Standard Error 4.6
|
-13.4 mmHg
Standard Error 3.7
|
-7.4 mmHg
Standard Error 3.5
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 2 postdose AM: 4 hour
|
1.7 mmHg
Standard Error 6.1
|
-7.1 mmHg
Standard Error 4.9
|
-9.4 mmHg
Standard Error 4.7
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 2 predose PM
|
4.6 mmHg
Standard Error 4.5
|
-7.1 mmHg
Standard Error 3.6
|
-2.4 mmHg
Standard Error 3.4
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 2 postdose PM: 1 hour
|
-3.8 mmHg
Standard Error 5.3
|
-2.2 mmHg
Standard Error 4.3
|
-3.1 mmHg
Standard Error 4.1
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 2 postdose PM: 4 hour
|
-5.0 mmHg
Standard Error 4.2
|
-9.7 mmHg
Standard Error 3.4
|
-8.0 mmHg
Standard Error 3.3
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 3 predose AM
|
-0.8 mmHg
Standard Error 4.0
|
-5.5 mmHg
Standard Error 3.2
|
-6.5 mmHg
Standard Error 3.1
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 3 postdose PM: 4 hour
|
-5.8 mmHg
Standard Error 4.8
|
-6.0 mmHg
Standard Error 3.9
|
-8.6 mmHg
Standard Error 3.7
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 4 predose AM
|
-0.8 mmHg
Standard Error 3.3
|
-7.0 mmHg
Standard Error 2.7
|
-8.9 mmHg
Standard Error 2.6
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 5 predose AM
|
-0.2 mmHg
Standard Error 3.6
|
-1.9 mmHg
Standard Error 2.9
|
-10.3 mmHg
Standard Error 2.8
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 6 predose AM
|
-4.3 mmHg
Standard Error 4.1
|
-11.0 mmHg
Standard Error 3.3
|
-8.6 mmHg
Standard Error 3.2
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 7 predose AM
|
-4.3 mmHg
Standard Error 4.8
|
-3.3 mmHg
Standard Error 3.8
|
-8.1 mmHg
Standard Error 3.7
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 7 postdose AM: 1 hour
|
-5.3 mmHg
Standard Error 4.4
|
-8.4 mmHg
Standard Error 3.5
|
-11.7 mmHg
Standard Error 3.4
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 7 postdose AM: 4 hour
|
1.3 mmHg
Standard Error 4.8
|
-8.2 mmHg
Standard Error 3.9
|
-15.9 mmHg
Standard Error 3.7
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 8 predose PM
|
-4.5 mmHg
Standard Error 5.5
|
-8.8 mmHg
Standard Error 4.4
|
-5.8 mmHg
Standard Error 4.2
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 9 predose AM
|
3.0 mmHg
Standard Error 3.7
|
-9.7 mmHg
Standard Error 3.0
|
-2.1 mmHg
Standard Error 2.9
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 10 predose AM
|
-1.3 mmHg
Standard Error 4.0
|
-9.3 mmHg
Standard Error 3.2
|
-5.1 mmHg
Standard Error 3.0
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 11 predose AM
|
3.8 mmHg
Standard Error 5.4
|
-12.3 mmHg
Standard Error 4.4
|
-4.5 mmHg
Standard Error 4.2
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 12 predose AM
|
-6.5 mmHg
Standard Error 4.1
|
-9.8 mmHg
Standard Error 3.3
|
-12.0 mmHg
Standard Error 3.1
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 13 predose AM
|
-1.6 mmHg
Standard Error 3.7
|
-13.5 mmHg
Standard Error 3.0
|
-8.1 mmHg
Standard Error 2.8
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 13 postdose AM: 1 hour
|
-2.4 mmHg
Standard Error 4.0
|
-16.6 mmHg
Standard Error 3.2
|
-14.2 mmHg
Standard Error 3.1
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 13 postdose AM: 4 hour
|
-3.9 mmHg
Standard Error 6.3
|
-15.6 mmHg
Standard Error 5.1
|
-13.7 mmHg
Standard Error 4.8
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 13 predose PM
|
-1.9 mmHg
Standard Error 4.0
|
-13.2 mmHg
Standard Error 3.2
|
-11.8 mmHg
Standard Error 3.1
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 14 predose AM
|
-3.7 mmHg
Standard Error 5.9
|
-9.5 mmHg
Standard Error 4.7
|
-9.8 mmHg
Standard Error 4.5
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 15/Discharge
|
2.1 mmHg
Standard Error 4.9
|
-6.0 mmHg
Standard Error 4.0
|
-3.0 mmHg
Standard Error 3.8
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 21/Follow-Up
|
-3.5 mmHg
Standard Error 4.3
|
1.3 mmHg
Standard Error 3.5
|
1.7 mmHg
Standard Error 3.3
|
—
|
|
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Day 42/End of Trial
|
3.3 mmHg
Standard Error 6.2
|
8.8 mmHg
Standard Error 5.0
|
-1.2 mmHg
Standard Error 4.8
|
—
|
PRIMARY outcome
Timeframe: Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 1 postdose AM: 4 hour
|
-0.3 mmHg
Standard Error 2.4
|
-3.2 mmHg
Standard Error 1.8
|
-7.4 mmHg
Standard Error 1.8
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 1 postdose AM: 8 hour
|
0.9 mmHg
Standard Error 2.3
|
-4.6 mmHg
Standard Error 1.7
|
-3.7 mmHg
Standard Error 1.7
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Study Baseline (Day 1 predose AM)
|
80.3 mmHg
Standard Error 6.9
|
75.5 mmHg
Standard Error 4.4
|
74.8 mmHg
Standard Error 5.9
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 1 postdose AM: 1 hour
|
-3.1 mmHg
Standard Error 2.4
|
-5.7 mmHg
Standard Error 1.8
|
-5.1 mmHg
Standard Error 1.8
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 1 predose PM
|
-1.3 mmHg
Standard Error 2.2
|
-4.9 mmHg
Standard Error 1.6
|
-3.5 mmHg
Standard Error 1.6
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 1 postdose PM: 1 hour
|
-0.9 mmHg
Standard Error 3.4
|
-5.9 mmHg
Standard Error 2.5
|
-3.7 mmHg
Standard Error 2.5
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 2 predose AM
|
3.1 mmHg
Standard Error 2.0
|
-1.3 mmHg
Standard Error 1.5
|
0 mmHg
Standard Error 1.5
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 2 postdose AM: 1 hour
|
-1.4 mmHg
Standard Error 2.4
|
-8.1 mmHg
Standard Error 1.8
|
-6.7 mmHg
Standard Error 1.8
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 2 postdose AM: 4 hour
|
2.2 mmHg
Standard Error 3.4
|
-3.1 mmHg
Standard Error 2.5
|
-6.2 mmHg
Standard Error 2.5
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 2 predose PM
|
1.9 mmHg
Standard Error 2.3
|
-3.7 mmHg
Standard Error 1.7
|
-2.6 mmHg
Standard Error 1.7
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 2 postdose PM: 1 hour
|
-2.2 mmHg
Standard Error 2.6
|
-2.7 mmHg
Standard Error 1.9
|
-4.4 mmHg
Standard Error 1.9
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 2 postdose PM: 4 hour
|
-3.9 mmHg
Standard Error 2.7
|
-6.3 mmHg
Standard Error 2.0
|
-5.4 mmHg
Standard Error 2.0
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 3 predose AM
|
-0.8 mmHg
Standard Error 2.5
|
-0.6 mmHg
Standard Error 1.8
|
-0.5 mmHg
Standard Error 1.8
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 3 postdose PM: 4 hour
|
-5.5 mmHg
Standard Error 3.0
|
-4.0 mmHg
Standard Error 2.2
|
-6.7 mmHg
Standard Error 2.2
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 4 predose AM
|
0.3 mmHg
Standard Error 2.2
|
-4.0 mmHg
Standard Error 1.6
|
-4.2 mmHg
Standard Error 1.6
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 5 predose AM
|
1.8 mmHg
Standard Error 2.2
|
-0.6 mmHg
Standard Error 1.6
|
-5.3 mmHg
Standard Error 1.6
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 6 predose AM
|
-0.5 mmHg
Standard Error 1.9
|
-3.3 mmHg
Standard Error 1.4
|
-5.2 mmHg
Standard Error 1.4
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 7 predose AM
|
0.9 mmHg
Standard Error 2.9
|
-3.2 mmHg
Standard Error 2.1
|
-3.4 mmHg
Standard Error 2.1
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 7 postdose AM: 1 hour
|
-1.7 mmHg
Standard Error 2.4
|
-6.0 mmHg
Standard Error 1.8
|
-7.4 mmHg
Standard Error 1.8
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 7 postdose AM: 4 hour
|
-6.1 mmHg
Standard Error 3.5
|
-5.1 mmHg
Standard Error 2.6
|
-5.9 mmHg
Standard Error 2.6
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 8 predose AM
|
0.6 mmHg
Standard Error 2.7
|
-3.9 mmHg
Standard Error 1.9
|
-2.2 mmHg
Standard Error 2.0
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 8 postdose AM: 1 hour
|
0 mmHg
Standard Error 2.4
|
-9.3 mmHg
Standard Error 1.8
|
-8.3 mmHg
Standard Error 1.8
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 8 postdose AM: 4 hour
|
-3.6 mmHg
Standard Error 2.8
|
-8.9 mmHg
Standard Error 2.0
|
-4.9 mmHg
Standard Error 2.1
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 8 predose PM
|
-3.3 mmHg
Standard Error 2.9
|
-4.1 mmHg
Standard Error 2.1
|
-3.0 mmHg
Standard Error 2.1
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 9 predose AM
|
0.6 mmHg
Standard Error 2.1
|
-4.3 mmHg
Standard Error 1.5
|
-1.6 mmHg
Standard Error 1.5
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 10 predose AM
|
0.1 mmHg
Standard Error 2.4
|
-3.7 mmHg
Standard Error 1.7
|
-5.0 mmHg
Standard Error 1.8
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 11 predose AM
|
2.2 mmHg
Standard Error 2.5
|
-6.4 mmHg
Standard Error 1.8
|
-3.1 mmHg
Standard Error 1.9
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 12 predose AM
|
-1.1 mmHg
Standard Error 2.0
|
-3.5 mmHg
Standard Error 1.5
|
-5.6 mmHg
Standard Error 1.5
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 13 predose AM
|
0.1 mmHg
Standard Error 2.2
|
-4.8 mmHg
Standard Error 1.6
|
-4.4 mmHg
Standard Error 1.6
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 13 postdose AM: 1 hour
|
-2.0 mmHg
Standard Error 2.1
|
-11.0 mmHg
Standard Error 1.6
|
-10.5 mmHg
Standard Error 1.6
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 13 postdose AM: 4 hour
|
-2.5 mmHg
Standard Error 2.9
|
-8.6 mmHg
Standard Error 2.1
|
-9.0 mmHg
Standard Error 2.2
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 13 predose PM
|
0.1 mmHg
Standard Error 2.7
|
-7.8 mmHg
Standard Error 2.0
|
-7.0 mmHg
Standard Error 2.0
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 14 predose AM
|
-4.4 mmHg
Standard Error 3.1
|
-6.1 mmHg
Standard Error 2.3
|
-4.1 mmHg
Standard Error 2.3
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 15/Discharge
|
-0.9 mmHg
Standard Error 2.4
|
-3.5 mmHg
Standard Error 1.8
|
-1.6 mmHg
Standard Error 1.8
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 21/Follow-Up
|
0.1 mmHg
Standard Error 1.8
|
-0.7 mmHg
Standard Error 1.3
|
0.3 mmHg
Standard Error 1.3
|
—
|
|
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Day 42/End of Trial
|
0.7 mmHg
Standard Error 3.3
|
2.8 mmHg
Standard Error 2.4
|
1.5 mmHg
Standard Error 2.4
|
—
|
PRIMARY outcome
Timeframe: Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Study Baseline Over Time in Supine Pulse
Study Baseline (Day 1 predose AM)
|
70.3 bpm
Standard Error 13.7
|
70.3 bpm
Standard Error 10.9
|
70.0 bpm
Standard Error 10.3
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 1 postdose AM: 1 hour
|
1.0 bpm
Standard Error 4.1
|
7.2 bpm
Standard Error 3.1
|
10.2 bpm
Standard Error 3.1
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 1 postdose AM: 4 hour
|
4.3 bpm
Standard Error 3.4
|
4.3 bpm
Standard Error 2.7
|
8.8 bpm
Standard Error 2.7
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 1 postdose AM: 8 hour
|
2.8 bpm
Standard Error 2.8
|
2.6 bpm
Standard Error 2.2
|
4.5 bpm
Standard Error 2.2
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 1 predose PM
|
0 bpm
Standard Error 2.7
|
5.1 bpm
Standard Error 2.1
|
5.3 bpm
Standard Error 2.1
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 1 postdose PM: 1 hour
|
2.3 bpm
Standard Error 2.8
|
4.6 bpm
Standard Error 2.2
|
3.7 bpm
Standard Error 2.2
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 2 predose AM
|
-2.6 bpm
Standard Error 2.3
|
-1.7 bpm
Standard Error 1.8
|
-1.9 bpm
Standard Error 1.8
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 2 postdose AM: 1 hour
|
7.0 bpm
Standard Error 4.1
|
9.5 bpm
Standard Error 3.1
|
11.3 bpm
Standard Error 3.1
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 2 postdose AM: 4 hour
|
3.2 bpm
Standard Error 3.0
|
6.5 bpm
Standard Error 2.3
|
10.2 bpm
Standard Error 2.3
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 2 predose PM
|
7.9 bpm
Standard Error 2.7
|
6.5 bpm
Standard Error 2.1
|
6.6 bpm
Standard Error 2.1
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 2 postdose PM: 1 hour
|
7.2 bpm
Standard Error 3.6
|
7.3 bpm
Standard Error 2.8
|
7.0 bpm
Standard Error 2.8
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 2 postdose PM: 4 hour
|
1.9 bpm
Standard Error 2.4
|
3.0 bpm
Standard Error 1.8
|
4.8 bpm
Standard Error 1.8
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 3 predose AM
|
0.2 bpm
Standard Error 2.3
|
-1.2 bpm
Standard Error 1.8
|
-0.2 bpm
Standard Error 1.8
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 3 postdose PM: 4 hour
|
3.0 bpm
Standard Error 2.9
|
0.7 bpm
Standard Error 2.2
|
5.2 bpm
Standard Error 2.2
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 4 predose AM
|
-4.1 bpm
Standard Error 2.6
|
2.8 bpm
Standard Error 2.0
|
0.9 bpm
Standard Error 2.0
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 5 predose AM
|
-3.3 bpm
Standard Error 2.3
|
-0.4 bpm
Standard Error 1.8
|
-0.6 bpm
Standard Error 1.8
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 6 predose AM
|
-0.8 bpm
Standard Error 2.9
|
1.5 bpm
Standard Error 2.3
|
-1.5 bpm
Standard Error 2.3
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 7 predose AM
|
-4.0 bpm
Standard Error 2.5
|
1.1 bpm
Standard Error 2.0
|
1.0 bpm
Standard Error 2.0
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 7 postdose AM: 1 hour
|
0.2 bpm
Standard Error 4.2
|
9.5 bpm
Standard Error 3.2
|
13.2 bpm
Standard Error 3.2
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 7 postdose AM: 4 hour
|
-2.6 bpm
Standard Error 2.6
|
4.4 bpm
Standard Error 2.0
|
8.8 bpm
Standard Error 2.0
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 8 predose AM
|
-2.8 bpm
Standard Error 2.6
|
-0.9 bpm
Standard Error 2.0
|
1.3 bpm
Standard Error 2.0
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 8 postdose AM: 1 hour
|
2.7 bpm
Standard Error 3.8
|
12.4 bpm
Standard Error 2.9
|
12.3 bpm
Standard Error 2.9
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 8 postdose AM: 4 hour
|
-0.6 bpm
Standard Error 3.0
|
7.1 bpm
Standard Error 2.3
|
7.7 bpm
Standard Error 2.3
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 8 predose PM
|
2.7 bpm
Standard Error 3.2
|
6.0 bpm
Standard Error 2.5
|
5.7 bpm
Standard Error 2.5
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 9 predose AM
|
-1.8 bpm
Standard Error 2.9
|
-0.3 bpm
Standard Error 2.3
|
0.5 bpm
Standard Error 2.3
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 10 predose AM
|
-3.0 bpm
Standard Error 3.2
|
1.3 bpm
Standard Error 2.4
|
2.1 bpm
Standard Error 2.4
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 11 predose AM
|
2.2 bpm
Standard Error 3.6
|
0.7 bpm
Standard Error 2.8
|
1.4 bpm
Standard Error 2.8
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 12 predose AM
|
-0.6 bpm
Standard Error 4.0
|
2.3 bpm
Standard Error 3.1
|
0.6 bpm
Standard Error 3.1
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 13 predose AM
|
-0.2 bpm
Standard Error 3.6
|
0.8 bpm
Standard Error 2.8
|
-0.1 bpm
Standard Error 2.8
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 13 postdose AM: 1 hour
|
0.3 bpm
Standard Error 3.2
|
7.3 bpm
Standard Error 2.5
|
10.2 bpm
Standard Error 2.5
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 13 postdose AM: 4 hour
|
-0.8 bpm
Standard Error 2.5
|
4.8 bpm
Standard Error 2.0
|
6.4 bpm
Standard Error 2.0
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 13 predose PM
|
5.0 bpm
Standard Error 3.0
|
4.5 bpm
Standard Error 2.3
|
7.0 bpm
Standard Error 2.3
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 14 predose AM
|
-3.1 bpm
Standard Error 3.0
|
0.7 bpm
Standard Error 2.3
|
0.1 bpm
Standard Error 2.3
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 15/Discharge
|
1.1 bpm
Standard Error 2.9
|
0.7 bpm
Standard Error 2.3
|
1.5 bpm
Standard Error 2.3
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 21/Follow-Up
|
-1.3 bpm
Standard Error 4.1
|
-2.0 bpm
Standard Error 3.2
|
5.4 bpm
Standard Error 3.2
|
—
|
|
Change From Study Baseline Over Time in Supine Pulse
Day 42/End of Trial
|
0.4 bpm
Standard Error 3.6
|
0.6 bpm
Standard Error 2.8
|
1.2 bpm
Standard Error 2.8
|
—
|
PRIMARY outcome
Timeframe: Baseline, Days 1-14, Day 15, 21, 42Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Baseline
|
33.3 percentage of participants
|
80.0 percentage of participants
|
60.0 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 1
|
100 percentage of participants
|
100 percentage of participants
|
100 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 2
|
66.7 percentage of participants
|
100 percentage of participants
|
100 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 3
|
66.7 percentage of participants
|
100 percentage of participants
|
90.0 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 4
|
50.0 percentage of participants
|
100 percentage of participants
|
90.0 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 5
|
50.0 percentage of participants
|
70.0 percentage of participants
|
90.0 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 6
|
66.7 percentage of participants
|
90.0 percentage of participants
|
90.0 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 7
|
50.0 percentage of participants
|
90.0 percentage of participants
|
90.0 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 8
|
83.3 percentage of participants
|
90.0 percentage of participants
|
100 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 9
|
33.3 percentage of participants
|
100 percentage of participants
|
70.0 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 10
|
33.3 percentage of participants
|
100 percentage of participants
|
70.0 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 11
|
50.0 percentage of participants
|
100 percentage of participants
|
70.0 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 12
|
50.0 percentage of participants
|
90.0 percentage of participants
|
80.0 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 13
|
66.7 percentage of participants
|
100 percentage of participants
|
100 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 14
|
50.0 percentage of participants
|
90.0 percentage of participants
|
80.0 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 15 / Discharge
|
33.3 percentage of participants
|
100 percentage of participants
|
70.0 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 21 / Follow-Up
|
50.0 percentage of participants
|
80.0 percentage of participants
|
50.0 percentage of participants
|
—
|
|
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Day 42 / End of Trial
|
33.3 percentage of participants
|
40.0 percentage of participants
|
60.0 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PMPopulation: Safety Population: participants who received at least 1 dose of study drug.
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Orthostatic Systolic Blood Pressure Over Time
Day 1, 1 hour PM
|
5.7 mmHg
Standard Deviation 10.2
|
0.7 mmHg
Standard Deviation 18.0
|
4.1 mmHg
Standard Deviation 11.4
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 1, 4 hour PM
|
4.3 mmHg
Standard Deviation 14.4
|
0.4 mmHg
Standard Deviation 14.8
|
6.4 mmHg
Standard Deviation 5.3
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 8, 1 hour AM
|
-2.5 mmHg
Standard Deviation 8.5
|
5.9 mmHg
Standard Deviation 14.7
|
1.7 mmHg
Standard Deviation 12.6
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 8, 4 hour AM
|
1.0 mmHg
Standard Deviation 12.3
|
2.9 mmHg
Standard Deviation 10.3
|
-1.7 mmHg
Standard Deviation 16.0
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 13, 1 hour AM
|
-1.5 mmHg
Standard Deviation 12.8
|
8.3 mmHg
Standard Deviation 13.7
|
1.4 mmHg
Standard Deviation 12.1
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 13, 4 hour AM
|
0.8 mmHg
Standard Deviation 7.4
|
4.1 mmHg
Standard Deviation 10.9
|
2.2 mmHg
Standard Deviation 11.7
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 13, 0 hour PM
|
3.8 mmHg
Standard Deviation 9.1
|
4.8 mmHg
Standard Deviation 14.2
|
3.2 mmHg
Standard Deviation 10.3
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day -1, 1 hour AM
|
-0.8 mmHg
Standard Deviation 11.9
|
2.0 mmHg
Standard Deviation 12.1
|
5.6 mmHg
Standard Deviation 11.5
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day -1, 4 hour AM
|
0.3 mmHg
Standard Deviation 6.4
|
2.9 mmHg
Standard Deviation 9.9
|
2.3 mmHg
Standard Deviation 11.5
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day -1, 0 hour PM
|
3.0 mmHg
Standard Deviation 10.5
|
1.7 mmHg
Standard Deviation 12.4
|
-0.1 mmHg
Standard Deviation 7.3
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day -1, 1 hour PM
|
3.8 mmHg
Standard Deviation 9.0
|
5.3 mmHg
Standard Deviation 13.8
|
3.1 mmHg
Standard Deviation 11.5
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 1, 0 hour AM
|
1.3 mmHg
Standard Deviation 9.6
|
5.2 mmHg
Standard Deviation 11.8
|
3.7 mmHg
Standard Deviation 12.7
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 1, 1 hour AM
|
9.7 mmHg
Standard Deviation 7.9
|
3.7 mmHg
Standard Deviation 15.8
|
2.5 mmHg
Standard Deviation 11.5
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 1, 4 hour AM
|
3.0 mmHg
Standard Deviation 14.6
|
12.1 mmHg
Standard Deviation 11.3
|
5.8 mmHg
Standard Deviation 8.3
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 1, 8 hour AM
|
5.3 mmHg
Standard Deviation 6.4
|
4.7 mmHg
Standard Deviation 12.4
|
5.1 mmHg
Standard Deviation 11.5
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 1, 0 hour PM
|
10.2 mmHg
Standard Deviation 10.5
|
4.1 mmHg
Standard Deviation 17.0
|
0.2 mmHg
Standard Deviation 10.3
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 2, 0 hour AM
|
-2.7 mmHg
Standard Deviation 11.0
|
2.5 mmHg
Standard Deviation 13.5
|
1.1 mmHg
Standard Deviation 10.3
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 2, 1 hour AM
|
-4.7 mmHg
Standard Deviation 15.0
|
2.9 mmHg
Standard Deviation 8.5
|
2.2 mmHg
Standard Deviation 8.6
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 2, 4 hour AM
|
-1.7 mmHg
Standard Deviation 11.4
|
5.8 mmHg
Standard Deviation 6.8
|
4.6 mmHg
Standard Deviation 10.6
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 2, 0 Hour PM
|
-6.0 mmHg
Standard Deviation 14.9
|
6.6 mmHg
Standard Deviation 11.9
|
2.3 mmHg
Standard Deviation 10.4
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 2, 1 hour PM
|
2.7 mmHg
Standard Deviation 14.4
|
5.0 mmHg
Standard Deviation 14.3
|
0.5 mmHg
Standard Deviation 14.0
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 2, 4 hour PM
|
0.8 mmHg
Standard Deviation 6.8
|
-0.7 mmHg
Standard Deviation 18.9
|
7.1 mmHg
Standard Deviation 13.1
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 7, 0 hour AM
|
1.0 mmHg
Standard Deviation 7.6
|
2.5 mmHg
Standard Deviation 19.1
|
4.9 mmHg
Standard Deviation 10.7
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 7, 1 hour AM
|
-2.0 mmHg
Standard Deviation 6.8
|
6.3 mmHg
Standard Deviation 11.7
|
-2.5 mmHg
Standard Deviation 8.0
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 7, 4 hour AM
|
-1.2 mmHg
Standard Deviation 10.8
|
4.7 mmHg
Standard Deviation 11.3
|
4.7 mmHg
Standard Deviation 14.1
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 8, 0 hour AM
|
-4.0 mmHg
Standard Deviation 13.7
|
6.5 mmHg
Standard Deviation 11.9
|
-1.1 mmHg
Standard Deviation 5.7
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 8, 0 hour PM
|
1.0 mmHg
Standard Deviation 8.4
|
5.0 mmHg
Standard Deviation 9.7
|
4.2 mmHg
Standard Deviation 8.8
|
—
|
|
Orthostatic Systolic Blood Pressure Over Time
Day 13, 0 hour AM
|
-2.0 mmHg
Standard Deviation 5.2
|
6.2 mmHg
Standard Deviation 13.7
|
1.3 mmHg
Standard Deviation 7.4
|
—
|
PRIMARY outcome
Timeframe: Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PMPopulation: Safety Population: participants who received at least 1 dose of study drug.
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Orthostatic Diastolic Blood Pressure Over Time
Day -1, 1 hour AM
|
1.8 mmHg
Standard Deviation 3.0
|
3.3 mmHg
Standard Deviation 6.8
|
6.3 mmHg
Standard Deviation 5.9
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day -1, 0 hour PM
|
8.2 mmHg
Standard Deviation 4.6
|
4.2 mmHg
Standard Deviation 5.6
|
3.4 mmHg
Standard Deviation 4.4
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day -1, 1 hour PM
|
5.7 mmHg
Standard Deviation 4.6
|
4.0 mmHg
Standard Deviation 6.8
|
4.5 mmHg
Standard Deviation 4.3
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 1, 0 hour AM
|
3.3 mmHg
Standard Deviation 5.2
|
4.2 mmHg
Standard Deviation 4.4
|
5.4 mmHg
Standard Deviation 4.6
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 1, 1 hour AM
|
5.3 mmHg
Standard Deviation 8.9
|
2.9 mmHg
Standard Deviation 5.1
|
3.4 mmHg
Standard Deviation 5.9
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 1, 4 hour AM
|
4.2 mmHg
Standard Deviation 4.1
|
6.1 mmHg
Standard Deviation 5.8
|
7.0 mmHg
Standard Deviation 5.0
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 1, 8 hour AM
|
5.3 mmHg
Standard Deviation 1.9
|
3.6 mmHg
Standard Deviation 4.5
|
4.9 mmHg
Standard Deviation 6.0
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 1, 0 hour PM
|
10.0 mmHg
Standard Deviation 6.8
|
2.8 mmHg
Standard Deviation 6.3
|
5.1 mmHg
Standard Deviation 6.2
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 13, 0 hour AM
|
2.7 mmHg
Standard Deviation 5.1
|
4.0 mmHg
Standard Deviation 6.8
|
3.9 mmHg
Standard Deviation 4.1
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 13, 1 hour AM
|
3.3 mmHg
Standard Deviation 4.3
|
5.8 mmHg
Standard Deviation 4.7
|
5.0 mmHg
Standard Deviation 7.1
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 13, 4 hour AM
|
0.7 mmHg
Standard Deviation 4.5
|
3.7 mmHg
Standard Deviation 4.3
|
5.4 mmHg
Standard Deviation 7.7
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 13, 0 hour PM
|
4.0 mmHg
Standard Deviation 3.2
|
5.1 mmHg
Standard Deviation 6.3
|
3.9 mmHg
Standard Deviation 3.8
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day -1, 4 hour AM
|
-0.5 mmHg
Standard Deviation 5.1
|
3.6 mmHg
Standard Deviation 8.2
|
5.5 mmHg
Standard Deviation 6.4
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 1, 1 hour PM
|
3.0 mmHg
Standard Deviation 4.3
|
5.2 mmHg
Standard Deviation 9.2
|
5.1 mmHg
Standard Deviation 4.3
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 1, 4 hour PM
|
6.8 mmHg
Standard Deviation 4.2
|
3.4 mmHg
Standard Deviation 7.3
|
7.7 mmHg
Standard Deviation 4.9
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 2, 0 hour AM
|
2.7 mmHg
Standard Deviation 2.0
|
3.3 mmHg
Standard Deviation 5.2
|
3.3 mmHg
Standard Deviation 6.0
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 2, 1 hour AM
|
3.0 mmHg
Standard Deviation 4.1
|
1.8 mmHg
Standard Deviation 5.8
|
5.2 mmHg
Standard Deviation 3.2
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 2, 4 hour AM
|
0.5 mmHg
Standard Deviation 2.4
|
3.8 mmHg
Standard Deviation 3.5
|
5.7 mmHg
Standard Deviation 5.3
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 2, 0 Hour PM
|
-2.7 mmHg
Standard Deviation 10.2
|
3.2 mmHg
Standard Deviation 7.4
|
4.7 mmHg
Standard Deviation 5.2
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 2, 1 hour PM
|
2.3 mmHg
Standard Deviation 5.6
|
0.9 mmHg
Standard Deviation 6.1
|
5.3 mmHg
Standard Deviation 5.1
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 2, 4 hour PM
|
5.8 mmHg
Standard Deviation 4.3
|
1.3 mmHg
Standard Deviation 10.0
|
8.7 mmHg
Standard Deviation 7.5
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 7, 0 hour AM
|
2.3 mmHg
Standard Deviation 3.4
|
2.9 mmHg
Standard Deviation 7.9
|
5.6 mmHg
Standard Deviation 6.2
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 7, 1 hour AM
|
1.8 mmHg
Standard Deviation 2.9
|
3.7 mmHg
Standard Deviation 5.5
|
2.4 mmHg
Standard Deviation 3.5
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 7, 4 hour AM
|
7.3 mmHg
Standard Deviation 9.0
|
4.8 mmHg
Standard Deviation 7.4
|
3.2 mmHg
Standard Deviation 6.5
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 8, 0 hour AM
|
3.3 mmHg
Standard Deviation 6.1
|
6.2 mmHg
Standard Deviation 7.1
|
4.8 mmHg
Standard Deviation 5.5
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 8, 1 hour AM
|
-1.3 mmHg
Standard Deviation 8.9
|
2.2 mmHg
Standard Deviation 8.4
|
3.8 mmHg
Standard Deviation 6.7
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 8, 4 hour AM
|
4.0 mmHg
Standard Deviation 2.6
|
1.9 mmHg
Standard Deviation 7.3
|
1.2 mmHg
Standard Deviation 7.3
|
—
|
|
Orthostatic Diastolic Blood Pressure Over Time
Day 8, 0 hour PM
|
5.0 mmHg
Standard Deviation 2.6
|
3.8 mmHg
Standard Deviation 4.5
|
4.2 mmHg
Standard Deviation 4.0
|
—
|
PRIMARY outcome
Timeframe: Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PMPopulation: Safety Population: participants who received at least 1 dose of study drug.
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Orthostatic Pulse Over Time
Day 1, 1 hour AM
|
8.7 bpm
Standard Deviation 6.6
|
9.7 bpm
Standard Deviation 5.9
|
12.9 bpm
Standard Deviation 6.9
|
—
|
|
Orthostatic Pulse Over Time
Day 1, 4 hour AM
|
7.7 bpm
Standard Deviation 7.4
|
11.0 bpm
Standard Deviation 6.1
|
10.1 bpm
Standard Deviation 8.4
|
—
|
|
Orthostatic Pulse Over Time
Day 1, 8 hour AM
|
10.0 bpm
Standard Deviation 4.7
|
9.9 bpm
Standard Deviation 6.3
|
10.5 bpm
Standard Deviation 4.6
|
—
|
|
Orthostatic Pulse Over Time
Day 1, 0 hour PM
|
14.8 bpm
Standard Deviation 9.9
|
9.1 bpm
Standard Deviation 6.6
|
7.7 bpm
Standard Deviation 4.1
|
—
|
|
Orthostatic Pulse Over Time
Day 1, 1 hour PM
|
9.3 bpm
Standard Deviation 6.2
|
10.8 bpm
Standard Deviation 7.2
|
11.1 bpm
Standard Deviation 6.6
|
—
|
|
Orthostatic Pulse Over Time
Day 1, 4 hour PM
|
16.5 bpm
Standard Deviation 12.7
|
14.5 bpm
Standard Deviation 7.2
|
16.5 bpm
Standard Deviation 10.0
|
—
|
|
Orthostatic Pulse Over Time
Day 2, 0 hour AM
|
9.0 bpm
Standard Deviation 3.0
|
10.4 bpm
Standard Deviation 7.0
|
10.5 bpm
Standard Deviation 4.7
|
—
|
|
Orthostatic Pulse Over Time
Day -1, 0 hour PM
|
15.3 bpm
Standard Deviation 15.0
|
10.1 bpm
Standard Deviation 4.7
|
9.8 bpm
Standard Deviation 4.9
|
—
|
|
Orthostatic Pulse Over Time
Day 2, 4 hour AM
|
11.2 bpm
Standard Deviation 9.2
|
8.4 bpm
Standard Deviation 6.5
|
8.8 bpm
Standard Deviation 6.2
|
—
|
|
Orthostatic Pulse Over Time
Day 2, 0 Hour PM
|
6.0 bpm
Standard Deviation 8.6
|
8.6 bpm
Standard Deviation 5.8
|
9.0 bpm
Standard Deviation 4.2
|
—
|
|
Orthostatic Pulse Over Time
Day 13, 4 hour AM
|
14.5 bpm
Standard Deviation 8.1
|
9.1 bpm
Standard Deviation 6.0
|
11.5 bpm
Standard Deviation 5.9
|
—
|
|
Orthostatic Pulse Over Time
Day 13, 0 hour PM
|
9.3 bpm
Standard Deviation 3.4
|
9.3 bpm
Standard Deviation 4.6
|
11.2 bpm
Standard Deviation 4.3
|
—
|
|
Orthostatic Pulse Over Time
Day -1, 1 hour AM
|
9.2 bpm
Standard Deviation 6.4
|
9.2 bpm
Standard Deviation 4.3
|
10.2 bpm
Standard Deviation 8.8
|
—
|
|
Orthostatic Pulse Over Time
Day -1, 4 hour AM
|
4.7 bpm
Standard Deviation 9.8
|
10.9 bpm
Standard Deviation 5.8
|
9.5 bpm
Standard Deviation 8.3
|
—
|
|
Orthostatic Pulse Over Time
Day -1, 1 hour PM
|
11.3 bpm
Standard Deviation 3.9
|
11.0 bpm
Standard Deviation 4.3
|
11.4 bpm
Standard Deviation 6.0
|
—
|
|
Orthostatic Pulse Over Time
Day 1, 0 hour AM
|
4.8 bpm
Standard Deviation 10.4
|
8.8 bpm
Standard Deviation 4.3
|
10.3 bpm
Standard Deviation 7.7
|
—
|
|
Orthostatic Pulse Over Time
Day 2, 1 hour AM
|
6.5 bpm
Standard Deviation 6.0
|
11.2 bpm
Standard Deviation 8.7
|
10.7 bpm
Standard Deviation 5.8
|
—
|
|
Orthostatic Pulse Over Time
Day 2, 1 hour PM
|
10.0 bpm
Standard Deviation 5.4
|
9.4 bpm
Standard Deviation 6.8
|
7.9 bpm
Standard Deviation 4.6
|
—
|
|
Orthostatic Pulse Over Time
Day 2, 4 hour PM
|
10.8 bpm
Standard Deviation 6.3
|
15.9 bpm
Standard Deviation 8.6
|
13.6 bpm
Standard Deviation 7.1
|
—
|
|
Orthostatic Pulse Over Time
Day 7, 0 hour AM
|
10.8 bpm
Standard Deviation 5.2
|
7.1 bpm
Standard Deviation 8.5
|
9.7 bpm
Standard Deviation 4.6
|
—
|
|
Orthostatic Pulse Over Time
Day 7, 1 hour AM
|
11.5 bpm
Standard Deviation 6.3
|
9.5 bpm
Standard Deviation 6.6
|
10.1 bpm
Standard Deviation 7.9
|
—
|
|
Orthostatic Pulse Over Time
Day 7, 4 hour AM
|
10.8 bpm
Standard Deviation 3.3
|
8.7 bpm
Standard Deviation 2.6
|
9.6 bpm
Standard Deviation 4.7
|
—
|
|
Orthostatic Pulse Over Time
Day 8, 0 hour AM
|
10.3 bpm
Standard Deviation 8.3
|
8.6 bpm
Standard Deviation 8.6
|
9.5 bpm
Standard Deviation 7.8
|
—
|
|
Orthostatic Pulse Over Time
Day 8, 1 hour AM
|
5.3 bpm
Standard Deviation 9.3
|
9.5 bpm
Standard Deviation 8.7
|
10.5 bpm
Standard Deviation 3.3
|
—
|
|
Orthostatic Pulse Over Time
Day 8, 4 hour AM
|
10.7 bpm
Standard Deviation 7.4
|
8.1 bpm
Standard Deviation 7.8
|
7.3 bpm
Standard Deviation 6.1
|
—
|
|
Orthostatic Pulse Over Time
Day 8, 0 hour PM
|
9.3 bpm
Standard Deviation 3.6
|
9.6 bpm
Standard Deviation 5.6
|
8.9 bpm
Standard Deviation 4.7
|
—
|
|
Orthostatic Pulse Over Time
Day 13, 0 hour AM
|
7.8 bpm
Standard Deviation 14.9
|
9.1 bpm
Standard Deviation 8.6
|
10.9 bpm
Standard Deviation 5.9
|
—
|
|
Orthostatic Pulse Over Time
Day 13, 1 hour AM
|
11.0 bpm
Standard Deviation 4.6
|
7.9 bpm
Standard Deviation 6.0
|
11.2 bpm
Standard Deviation 7.5
|
—
|
PRIMARY outcome
Timeframe: Time Matched Baseline (Day -1), Days 1, 7, and 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
n=20 Participants
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure
Change at Day 7
|
-3.54 mmHg
Standard Error 2.68
|
-6.77 mmHg
Standard Error 2.07
|
-3.03 mmHg
Standard Error 2.04
|
-4.90 mmHg
Standard Error 1.45
|
|
Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure
Change at Day 14
|
-4.87 mmHg
Standard Error 3.17
|
-7.58 mmHg
Standard Error 2.59
|
-6.74 mmHg
Standard Error 2.39
|
-7.16 mmHg
Standard Error 1.75
|
|
Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure
Time Matched Baseline (Day -1)
|
132.34 mmHg
Standard Error 8.22
|
126.40 mmHg
Standard Error 11.07
|
129.00 mmHg
Standard Error 6.48
|
127.70 mmHg
Standard Error 8.93
|
|
Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure
Change at Day 1
|
-0.60 mmHg
Standard Error 2.39
|
-3.92 mmHg
Standard Error 1.84
|
-3.15 mmHg
Standard Error 1.81
|
-3.53 mmHg
Standard Error 1.29
|
PRIMARY outcome
Timeframe: Time Matched Baseline (Day -1), Days 1, 7, and 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
Time Matched Baseline (Day -1)
|
136.99 mmHg
Standard Error 8.42
|
130.64 mmHg
Standard Error 10.82
|
132.28 mmHg
Standard Error 7.07
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
Change at Day 1
|
-0.74 mmHg
Standard Error 2.81
|
-7.80 mmHg
Standard Error 2.14
|
-4.93 mmHg
Standard Error 2.12
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
Change at Day 7
|
-5.27 mmHg
Standard Error 2.89
|
-9.09 mmHg
Standard Error 2.20
|
-3.85 mmHg
Standard Error 2.17
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
Change at Day 14
|
-6.37 mmHg
Standard Error 3.62
|
-12.81 mmHg
Standard Error 2.92
|
-7.40 mmHg
Standard Error 2.71
|
—
|
PRIMARY outcome
Timeframe: Time Matched Baseline (Day -1), Days 1, 7, and 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure
Change at Day 7
|
-1.42 mmHg
Standard Error 2.93
|
-4.54 mmHg
Standard Error 2.28
|
-2.25 mmHg
Standard Error 2.25
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure
Time Matched Baseline (Day -1)
|
126.76 mmHg
Standard Error 9.36
|
121.77 mmHg
Standard Error 12.26
|
125.26 mmHg
Standard Error 7.24
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure
Change at Day 1
|
0.11 mmHg
Standard Error 2.55
|
-0.11 mmHg
Standard Error 1.98
|
-1.50 mmHg
Standard Error 1.96
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure
Change at Day 14
|
-3.25 mmHg
Standard Error 3.17
|
-2.38 mmHg
Standard Error 2.63
|
-6.23 mmHg
Standard Error 2.44
|
—
|
PRIMARY outcome
Timeframe: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdosePopulation: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Time-matched baseline (Day -1): 0-4 hours
|
134.45 mmHg
Standard Error 8.01
|
128.18 mmHg
Standard Error 9.90
|
128.38 mmHg
Standard Error 7.33
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Time-matched baseline (Day -1): 8-12 hours
|
140.46 mmHg
Standard Error 9.12
|
133.67 mmHg
Standard Error 11.90
|
135.93 mmHg
Standard Error 8.51
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Time-matched baseline (Day -1): 12-16 hours
|
130.31 mmHg
Standard Error 9.75
|
124.00 mmHg
Standard Error 11.93
|
128.44 mmHg
Standard Error 11.32
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 1, 0-4 hours
|
-1.61 mmHg
Standard Error 3.02
|
-7.15 mmHg
Standard Error 2.27
|
-4.08 mmHg
Standard Error 2.27
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 1, 4-8 hours
|
-0.62 mmHg
Standard Error 3.51
|
-8.67 mmHg
Standard Error 2.70
|
-8.89 mmHg
Standard Error 2.67
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 1, 12-16 hours
|
-4.83 mmHg
Standard Error 3.04
|
-1.46 mmHg
Standard Error 2.37
|
-2.00 mmHg
Standard Error 2.34
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 1, 20-24 hours
|
2.08 mmHg
Standard Error 3.04
|
1.27 mmHg
Standard Error 2.37
|
-0.55 mmHg
Standard Error 2.27
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 7, 4-8 hours
|
-6.24 mmHg
Standard Error 3.44
|
-9.13 mmHg
Standard Error 2.65
|
-4.07 mmHg
Standard Error 2.62
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 7, 8-12 hours
|
-3.70 mmHg
Standard Error 3.65
|
-7.93 mmHg
Standard Error 2.80
|
-2.33 mmHg
Standard Error 2.76
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 7, 20-24 hours
|
-1.10 mmHg
Standard Error 3.74
|
-4.94 mmHg
Standard Error 2.91
|
-0.33 mmHg
Standard Error 2.80
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 14, 0-4 hours
|
-6.67 mmHg
Standard Error 3.92
|
-13.80 mmHg
Standard Error 3.10
|
-5.01 mmHg
Standard Error 2.90
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 14, 4-8 hours
|
-7.36 mmHg
Standard Error 3.62
|
-13.67 mmHg
Standard Error 2.95
|
-8.53 mmHg
Standard Error 2.75
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 14, 16-20 hours
|
-1.06 mmHg
Standard Error 3.53
|
-2.79 mmHg
Standard Error 2.89
|
-6.61 mmHg
Standard Error 2.74
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 14, 20-24 hours
|
-2.98 mmHg
Standard Error 3.82
|
-1.00 mmHg
Standard Error 3.17
|
-1.91 mmHg
Standard Error 2.84
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Time-matched baseline (Day -1): 4-8 hours
|
136.10 mmHg
Standard Error 9.69
|
130.04 mmHg
Standard Error 13.15
|
132.53 mmHg
Standard Error 6.83
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Time-matched baseline (Day -1): 16-20 hours
|
120.34 mmHg
Standard Error 8.79
|
119.75 mmHg
Standard Error 14.51
|
120.41 mmHg
Standard Error 11.00
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Time-matched baseline (Day -1): 20-24 hours
|
132.10 mmHg
Standard Error 11.62
|
122.77 mmHg
Standard Error 9.60
|
128.13 mmHg
Standard Error 7.19
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 1, 8-12 hours
|
1.21 mmHg
Standard Error 3.80
|
-8.14 mmHg
Standard Error 2.91
|
-1.84 mmHg
Standard Error 2.88
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 1, 16-20 hours
|
3.77 mmHg
Standard Error 4.12
|
-0.66 mmHg
Standard Error 3.19
|
-1.08 mmHg
Standard Error 3.19
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 7, 0-4 hours
|
-5.14 mmHg
Standard Error 3.14
|
-10.68 mmHg
Standard Error 2.35
|
-5.15 mmHg
Standard Error 2.35
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 7, 12-16 hours
|
-4.46 mmHg
Standard Error 3.66
|
-5.03 mmHg
Standard Error 2.86
|
-1.97 mmHg
Standard Error 2.82
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 7, 16-20 hours
|
2.75 mmHg
Standard Error 3.98
|
-5.14 mmHg
Standard Error 3.08
|
-3.74 mmHg
Standard Error 3.08
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 14, 8-12 hours
|
-4.42 mmHg
Standard Error 4.41
|
-11.43 mmHg
Standard Error 3.58
|
-8.53 mmHg
Standard Error 3.31
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Day 14, 12-16 hours
|
-5.28 mmHg
Standard Error 4.14
|
-3.52 mmHg
Standard Error 3.43
|
-8.75 mmHg
Standard Error 3.18
|
—
|
PRIMARY outcome
Timeframe: Time Matched Baseline (Day -1), Days 1, 7, and 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
n=20 Participants
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure
Change at Day 1
|
-0.68 mmHg
Standard Error 1.61
|
-2.80 mmHg
Standard Error 1.20
|
-3.07 mmHg
Standard Error 1.19
|
-2.94 mmHg
Standard Error 0.85
|
|
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure
Change at Day 7
|
-1.84 mmHg
Standard Error 1.83
|
-5.24 mmHg
Standard Error 1.37
|
-3.46 mmHg
Standard Error 1.35
|
-4.35 mmHg
Standard Error 0.97
|
|
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure
Time Matched Baseline (Day -1)
|
96.44 mmHg
Standard Error 8.38
|
90.27 mmHg
Standard Error 6.89
|
91.14 mmHg
Standard Error 5.54
|
90.71 mmHg
Standard Error 6.10
|
|
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure
Change at Day 14
|
-1.55 mmHg
Standard Error 2.28
|
-6.50 mmHg
Standard Error 1.79
|
-6.05 mmHg
Standard Error 1.65
|
-6.28 mmHg
Standard Error 1.23
|
PRIMARY outcome
Timeframe: Time Matched Baseline (Day -1), Days 1, 7, and 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure
Time Matched Baseline (Day -1)
|
100.09 mmHg
Standard Error 7.14
|
93.31 mmHg
Standard Error 7.36
|
94.00 mmHg
Standard Error 5.54
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure
Change at Day 1
|
-0.20 mmHg
Standard Error 2.24
|
-5.07 mmHg
Standard Error 1.65
|
-5.22 mmHg
Standard Error 1.63
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure
Change at Day 7
|
-2.60 mmHg
Standard Error 2.01
|
-6.82 mmHg
Standard Error 1.48
|
-4.75 mmHg
Standard Error 1.46
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure
Change at Day 14
|
-1.97 mmHg
Standard Error 2.50
|
-10.71 mmHg
Standard Error 1.94
|
-7.31 mmHg
Standard Error 1.79
|
—
|
PRIMARY outcome
Timeframe: Time Matched Baseline (Day -1), Days 1, 7, and 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure
Time Matched Baseline (Day -1)
|
91.93 mmHg
Standard Error 10.03
|
86.85 mmHg
Standard Error 7.57
|
87.77 mmHg
Standard Error 6.37
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure
Change at Day 1
|
-0.39 mmHg
Standard Error 1.67
|
-0.84 mmHg
Standard Error 1.27
|
-1.10 mmHg
Standard Error 1.26
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure
Change at Day 7
|
-0.47 mmHg
Standard Error 2.07
|
-3.79 mmHg
Standard Error 1.57
|
-2.20 mmHg
Standard Error 1.56
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure
Change at Day 14
|
-0.54 mmHg
Standard Error 2.46
|
-2.42 mmHg
Standard Error 1.97
|
-4.83 mmHg
Standard Error 1.84
|
—
|
PRIMARY outcome
Timeframe: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdosePopulation: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 1, 12-16 hours
|
-2.21 mmHg
Standard Error 1.90
|
-1.84 mmHg
Standard Error 1.47
|
-2.23 mmHg
Standard Error 1.44
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Time-matched baseline (Day -1): 4-8 hours
|
98.92 mmHg
Standard Error 8.64
|
92.27 mmHg
Standard Error 7.73
|
93.98 mmHg
Standard Error 4.94
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Time-matched baseline (Day -1): 8-12 hours
|
103.25 mmHg
Standard Error 8.66
|
96.20 mmHg
Standard Error 9.50
|
96.76 mmHg
Standard Error 8.22
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Time-matched baseline (Day -1): 12-16 hours
|
93.31 mmHg
Standard Error 9.82
|
87.07 mmHg
Standard Error 6.75
|
90.02 mmHg
Standard Error 8.80
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Time-matched baseline (Day -1): 16-20 hours
|
87.48 mmHg
Standard Error 10.42
|
85.54 mmHg
Standard Error 9.68
|
83.70 mmHg
Standard Error 9.24
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 1, 0-4 hours
|
-0.40 mmHg
Standard Error 2.61
|
-4.84 mmHg
Standard Error 1.86
|
-5.57 mmHg
Standard Error 1.88
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 1, 4-8 hours
|
0.24 mmHg
Standard Error 2.86
|
-4.98 mmHg
Standard Error 2.15
|
-7.97 mmHg
Standard Error 2.11
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 1, 8-12 hours
|
0.84 mmHg
Standard Error 2.87
|
-5.87 mmHg
Standard Error 2.15
|
-2.30 mmHg
Standard Error 2.14
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 1, 20-24 hours
|
0.99 mmHg
Standard Error 2.20
|
0.25 mmHg
Standard Error 1.63
|
-0.13 mmHg
Standard Error 1.60
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 7, 8-12 hours
|
-1.71 mmHg
Standard Error 2.33
|
-6.47 mmHg
Standard Error 1.74
|
-2.96 mmHg
Standard Error 1.73
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 7, 12-16 hours
|
-2.35 mmHg
Standard Error 2.42
|
-4.46 mmHg
Standard Error 1.86
|
-2.30 mmHg
Standard Error 1.83
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 7, 16-20 hours
|
2.93 mmHg
Standard Error 2.89
|
-3.73 mmHg
Standard Error 2.23
|
-3.45 mmHg
Standard Error 2.24
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 14, 0-4 hours
|
-2.65 mmHg
Standard Error 2.67
|
-10.39 mmHg
Standard Error 1.99
|
-6.51 mmHg
Standard Error 1.86
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 14, 4-8 hours
|
-2.26 mmHg
Standard Error 2.38
|
-11.78 mmHg
Standard Error 1.89
|
-7.91 mmHg
Standard Error 1.74
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 14, 12-16 hours
|
-1.55 mmHg
Standard Error 3.31
|
-2.91 mmHg
Standard Error 2.71
|
-6.50 mmHg
Standard Error 2.49
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 14, 16-20 hours
|
0.05 mmHg
Standard Error 2.75
|
-3.38 mmHg
Standard Error 2.23
|
-5.33 mmHg
Standard Error 2.12
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 14, 20-24 hours
|
-0.49 mmHg
Standard Error 2.70
|
-0.57 mmHg
Standard Error 2.12
|
-2.38 mmHg
Standard Error 1.95
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Time-matched baseline (Day -1): 0-4 hours
|
98.10 mmHg
Standard Error 5.10
|
91.52 mmHg
Standard Error 7.00
|
91.16 mmHg
Standard Error 4.64
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Time-matched baseline (Day -1): 20-24 hours
|
97.62 mmHg
Standard Error 11.48
|
89.30 mmHg
Standard Error 6.40
|
90.96 mmHg
Standard Error 6.46
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 1, 16-20 hours
|
1.47 mmHg
Standard Error 2.96
|
-0.86 mmHg
Standard Error 2.28
|
-0.97 mmHg
Standard Error 2.29
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 7, 0-4 hours
|
-2.77 mmHg
Standard Error 2.13
|
-7.90 mmHg
Standard Error 1.52
|
-6.41 mmHg
Standard Error 1.53
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 7, 4-8 hours
|
-2.54 mmHg
Standard Error 2.73
|
-6.46 mmHg
Standard Error 2.06
|
-4.99 mmHg
Standard Error 2.02
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 7, 20-24 hours
|
-1.18 mmHg
Standard Error 2.62
|
-3.47 mmHg
Standard Error 1.94
|
-1.35 mmHg
Standard Error 1.91
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Day 14, 8-12 hours
|
-1.27 mmHg
Standard Error 3.35
|
-9.89 mmHg
Standard Error 2.65
|
-7.32 mmHg
Standard Error 2.46
|
—
|
PRIMARY outcome
Timeframe: Time Matched Baseline (Day -1), Days 1, 7, and 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
n=20 Participants
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure
Time Matched Baseline (Day -1)
|
77.37 mmHg
Standard Error 9.26
|
71.57 mmHg
Standard Error 8.58
|
71.50 mmHg
Standard Error 6.33
|
71.53 mmHg
Standard Error 7.34
|
|
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure
Change at Day 1
|
-1.73 mmHg
Standard Error 1.29
|
-2.53 mmHg
Standard Error 0.96
|
-2.82 mmHg
Standard Error 0.96
|
-2.67 mmHg
Standard Error 0.69
|
|
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure
Change at Day 14
|
-1.36 mmHg
Standard Error 2.04
|
-5.33 mmHg
Standard Error 1.61
|
-5.53 mmHg
Standard Error 1.51
|
-5.43 mmHg
Standard Error 1.11
|
|
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure
Change at Day 7
|
-1.60 mmHg
Standard Error 1.49
|
-4.27 mmHg
Standard Error 1.12
|
-3.44 mmHg
Standard Error 1.12
|
-3.86 mmHg
Standard Error 0.80
|
PRIMARY outcome
Timeframe: Time Matched Baseline (Day -1), Days 1, 7, and 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure
Time Matched Baseline (Day -1)
|
80.71 mmHg
Standard Error 8.65
|
74.31 mmHg
Standard Error 9.19
|
74.20 mmHg
Standard Error 6.45
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure
Change at Day 1
|
-0.88 mmHg
Standard Error 1.76
|
-4.28 mmHg
Standard Error 1.31
|
-4.47 mmHg
Standard Error 1.31
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure
Change at Day 7
|
-2.36 mmHg
Standard Error 1.61
|
-5.66 mmHg
Standard Error 1.20
|
-4.36 mmHg
Standard Error 1.20
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure
Change at Day 14
|
-1.59 mmHg
Standard Error 2.03
|
-8.88 mmHg
Standard Error 1.59
|
-6.69 mmHg
Standard Error 1.50
|
—
|
PRIMARY outcome
Timeframe: Time Matched Baseline (Day -1), Days 1, 7, and 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure
Time Matched Baseline (Day -1)
|
73.42 mmHg
Standard Error 10.04
|
68.44 mmHg
Standard Error 8.60
|
68.36 mmHg
Standard Error 6.80
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure
Change at Day 1
|
-2.02 mmHg
Standard Error 1.51
|
-1.03 mmHg
Standard Error 1.14
|
-1.46 mmHg
Standard Error 1.14
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure
Change at Day 7
|
-0.42 mmHg
Standard Error 1.94
|
-2.96 mmHg
Standard Error 1.47
|
-2.68 mmHg
Standard Error 1.47
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure
Change at Day 14
|
-0.81 mmHg
Standard Error 2.41
|
-1.84 mmHg
Standard Error 1.92
|
-4.48 mmHg
Standard Error 1.81
|
—
|
PRIMARY outcome
Timeframe: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdosePopulation: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 1, 0-4 hours
|
-0.57 mmHg
Standard Error 1.98
|
-3.15 mmHg
Standard Error 1.45
|
-4.63 mmHg
Standard Error 1.47
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 1, 4-8 hours
|
-1.02 mmHg
Standard Error 2.15
|
-4.88 mmHg
Standard Error 1.61
|
-5.75 mmHg
Standard Error 1.61
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 7, 4-8 hours
|
-2.55 mmHg
Standard Error 2.45
|
-5.94 mmHg
Standard Error 1.83
|
-3.61 mmHg
Standard Error 1.84
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 7, 8-12 hours
|
-2.16 mmHg
Standard Error 2.01
|
-4.98 mmHg
Standard Error 1.52
|
-3.52 mmHg
Standard Error 1.51
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 7, 16-20 hours
|
2.29 mmHg
Standard Error 2.62
|
-3.57 mmHg
Standard Error 2.01
|
-3.91 mmHg
Standard Error 2.03
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 14, 0-4 hours
|
-2.02 mmHg
Standard Error 2.16
|
-8.92 mmHg
Standard Error 1.66
|
-6.06 mmHg
Standard Error 1.57
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 14, 20-24 hours
|
0.50 mmHg
Standard Error 2.64
|
0.06 mmHg
Standard Error 2.08
|
-1.48 mmHg
Standard Error 1.95
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Time Matched Baseline (Day -1): 0-4 hours
|
78.96 mmHg
Standard Error 8.70
|
72.48 mmHg
Standard Error 8.58
|
71.58 mmHg
Standard Error 5.46
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Time Matched Baseline (Day -1): 4-8 hours
|
79.85 mmHg
Standard Error 9.34
|
73.96 mmHg
Standard Error 8.85
|
73.79 mmHg
Standard Error 6.71
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Time Matched Baseline (Day -1): 8-12 hours
|
83.31 mmHg
Standard Error 8.49
|
76.47 mmHg
Standard Error 11.76
|
77.13 mmHg
Standard Error 8.49
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Time Matched Baseline (Day -1): 12-16 hours
|
74.27 mmHg
Standard Error 10.88
|
68.10 mmHg
Standard Error 7.92
|
70.29 mmHg
Standard Error 8.87
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Time Matched Baseline (Day -1): 16-20 hours
|
70.07 mmHg
Standard Error 9.16
|
67.89 mmHg
Standard Error 10.04
|
64.87 mmHg
Standard Error 8.26
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Time Matched Baseline (Day -1): 20-24 hours
|
77.61 mmHg
Standard Error 10.95
|
70.57 mmHg
Standard Error 8.35
|
71.04 mmHg
Standard Error 7.34
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 1, 8-12 hours
|
-0.08 mmHg
Standard Error 2.64
|
-5.18 mmHg
Standard Error 1.99
|
-3.04 mmHg
Standard Error 1.99
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 1, 12-16 hours
|
-2.99 mmHg
Standard Error 2.10
|
-2.12 mmHg
Standard Error 1.61
|
-2.44 mmHg
Standard Error 1.59
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 1, 16-20 hours
|
-1.41 mmHg
Standard Error 2.56
|
-1.97 mmHg
Standard Error 1.96
|
-1.87 mmHg
Standard Error 1.99
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 1, 20-24 hours
|
-0.13 mmHg
Standard Error 1.89
|
1.59 mmHg
Standard Error 1.41
|
0.12 mmHg
Standard Error 1.40
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 7, 0-4 hours
|
-1.88 mmHg
Standard Error 1.56
|
-6.31 mmHg
Standard Error 1.14
|
-6.05 mmHg
Standard Error 1.15
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 7, 12-16 hours
|
-2.18 mmHg
Standard Error 2.32
|
-3.37 mmHg
Standard Error 1.78
|
-3.45 mmHg
Standard Error 1.75
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 7, 20-24 hours
|
-0.13 mmHg
Standard Error 2.37
|
-1.74 mmHg
Standard Error 1.77
|
-0.76 mmHg
Standard Error 1.76
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 14, 4-8 hours
|
-1.52 mmHg
Standard Error 1.98
|
-9.77 mmHg
Standard Error 1.56
|
-7.07 mmHg
Standard Error 1.47
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 14, 8-12 hours
|
-0.98 mmHg
Standard Error 2.99
|
-8.06 mmHg
Standard Error 2.39
|
-6.83 mmHg
Standard Error 2.24
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 14, 12-16 hours
|
-0.91 mmHg
Standard Error 3.19
|
-2.32 mmHg
Standard Error 2.59
|
-6.07 mmHg
Standard Error 2.40
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Day 14, 16-20 hours
|
-0.94 mmHg
Standard Error 2.91
|
-3.30 mmHg
Standard Error 2.34
|
-5.44 mmHg
Standard Error 2.24
|
—
|
PRIMARY outcome
Timeframe: Time Matched Baseline (Day -1), Days 1, 7, and 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
n=20 Participants
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse
Time Matched Baseline (Day -1)
|
75.08 bpm
Standard Error 14.09
|
72.81 bpm
Standard Error 10.79
|
75.40 bpm
Standard Error 10.84
|
74.10 bpm
Standard Error 10.61
|
|
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse
Change at Day 1
|
-0.90 bpm
Standard Error 1.25
|
2.29 bpm
Standard Error 0.97
|
2.64 bpm
Standard Error 0.97
|
2.47 bpm
Standard Error 0.69
|
|
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse
Change at Day 7
|
-1.92 bpm
Standard Error 1.38
|
2.67 bpm
Standard Error 1.08
|
2.57 bpm
Standard Error 1.07
|
2.62 bpm
Standard Error 0.76
|
|
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse
Change at Day 14
|
-0.45 bpm
Standard Error 1.50
|
2.12 bpm
Standard Error 1.23
|
2.71 bpm
Standard Error 1.16
|
2.42 bpm
Standard Error 0.84
|
PRIMARY outcome
Timeframe: Time Matched Baseline (Day -1), Days 1, 7, and 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse
Time Matched Baseline (Day -1)
|
76.81 bpm
Standard Error 15.00
|
75.98 bpm
Standard Error 12.84
|
78.18 bpm
Standard Error 11.47
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse
Change at Day 1
|
0.14 bpm
Standard Error 1.84
|
2.30 bpm
Standard Error 1.42
|
4.23 bpm
Standard Error 1.43
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse
Change at Day 7
|
-1.80 bpm
Standard Error 1.51
|
2.75 bpm
Standard Error 1.17
|
2.22 bpm
Standard Error 1.17
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse
Change at Day 14
|
-0.46 bpm
Standard Error 1.59
|
2.66 bpm
Standard Error 1.30
|
3.28 bpm
Standard Error 1.23
|
—
|
PRIMARY outcome
Timeframe: Time Matched Baseline (Day -1), Days 1, 7, and 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse
Change at Day 1
|
-2.01 bpm
Standard Error 1.21
|
2.29 bpm
Standard Error 0.94
|
0.93 bpm
Standard Error 0.94
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse
Change at Day 7
|
-2.24 bpm
Standard Error 1.63
|
2.57 bpm
Standard Error 1.27
|
2.86 bpm
Standard Error 1.26
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse
Time Matched Baseline (Day -1)
|
73.43 bpm
Standard Error 13.39
|
69.62 bpm
Standard Error 8.91
|
72.54 bpm
Standard Error 10.46
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse
Change at Day 14
|
-0.40 bpm
Standard Error 1.79
|
1.48 bpm
Standard Error 1.46
|
2.15 bpm
Standard Error 1.38
|
—
|
PRIMARY outcome
Timeframe: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdosePopulation: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 7, 20-24 hours
|
0.23 bpm
Standard Error 1.85
|
1.91 bpm
Standard Error 1.44
|
4.26 bpm
Standard Error 1.44
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 14, 0-4 hours
|
0.77 bpm
Standard Error 1.95
|
4.82 bpm
Standard Error 1.59
|
4.53 bpm
Standard Error 1.51
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 14, 4-8 hours
|
-2.85 bpm
Standard Error 2.56
|
2.33 bpm
Standard Error 2.09
|
2.76 bpm
Standard Error 1.99
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 14, 8-12 hours
|
0.89 bpm
Standard Error 1.91
|
0.68 bpm
Standard Error 1.56
|
2.50 bpm
Standard Error 1.48
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Time Matched Baseline (Day -1): 0-4 hours
|
73.52 bpm
Standard Error 14.02
|
73.89 bpm
Standard Error 12.23
|
76.46 bpm
Standard Error 9.48
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Time Matched Baseline (Day -1): 4-8 hours
|
77.65 bpm
Standard Error 15.57
|
76.88 bpm
Standard Error 15.09
|
79.91 bpm
Standard Error 14.33
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Time Matched Baseline (Day -1): 8-12 hours
|
79.00 bpm
Standard Error 15.50
|
77.34 bpm
Standard Error 11.42
|
78.21 bpm
Standard Error 11.67
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Time Matched Baseline (Day -1): 12-16 hours
|
78.60 bpm
Standard Error 15.22
|
72.93 bpm
Standard Error 9.38
|
75.36 bpm
Standard Error 11.89
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Time Matched Baseline (Day -1): 16-20 hours
|
72.08 bpm
Standard Error 13.37
|
67.79 bpm
Standard Error 8.80
|
70.51 bpm
Standard Error 10.23
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Time Matched Baseline (Day -1): 20-24 hours
|
68.05 bpm
Standard Error 11.26
|
67.97 bpm
Standard Error 8.75
|
71.45 bpm
Standard Error 10.35
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 1, 0-4 hours
|
0.87 bpm
Standard Error 2.07
|
7.68 bpm
Standard Error 1.60
|
7.42 bpm
Standard Error 1.60
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 1, 4-8 hours
|
1.18 bpm
Standard Error 2.76
|
0.23 bpm
Standard Error 2.14
|
3.02 bpm
Standard Error 2.14
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 1, 8-12 hours
|
-0.96 bpm
Standard Error 2.14
|
-1.33 bpm
Standard Error 1.65
|
2.15 bpm
Standard Error 1.65
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 1, 12-16 hours
|
-4.33 bpm
Standard Error 1.68
|
2.13 bpm
Standard Error 1.30
|
1.24 bpm
Standard Error 1.29
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 1, 16-20 hours
|
-1.67 bpm
Standard Error 1.24
|
1.95 bpm
Standard Error 0.97
|
0.73 bpm
Standard Error 0.96
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 1, 20-24 hours
|
0.76 bpm
Standard Error 1.77
|
2.50 bpm
Standard Error 1.37
|
1.09 bpm
Standard Error 1.38
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 7, 0-4 hours
|
-0.09 bpm
Standard Error 2.11
|
4.27 bpm
Standard Error 1.63
|
5.32 bpm
Standard Error 1.64
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 7, 4-8 hours
|
-2.94 bpm
Standard Error 1.72
|
1.95 bpm
Standard Error 1.34
|
1.36 bpm
Standard Error 1.34
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 7, 8-12 hours
|
-2.25 bpm
Standard Error 1.78
|
1.79 bpm
Standard Error 1.38
|
0.01 bpm
Standard Error 1.38
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 7, 12-16 hours
|
-4.05 bpm
Standard Error 1.89
|
2.85 bpm
Standard Error 1.46
|
2.10 bpm
Standard Error 1.45
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 7, 16-20 hours
|
-2.56 bpm
Standard Error 1.87
|
2.44 bpm
Standard Error 1.45
|
2.78 bpm
Standard Error 1.44
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 14, 12-16 hours
|
-3.74 bpm
Standard Error 2.33
|
1.35 bpm
Standard Error 1.89
|
1.56 bpm
Standard Error 1.79
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 14, 16-20 hours
|
-0.88 bpm
Standard Error 1.98
|
0.43 bpm
Standard Error 1.61
|
2.06 bpm
Standard Error 1.53
|
—
|
|
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Day 14, 20-24 hours
|
4.14 bpm
Standard Error 2.31
|
2.80 bpm
Standard Error 1.88
|
3.00 bpm
Standard Error 1.80
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 13 predose AMPopulation: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment. Participants with an assessment.
RHI is a measure of the extent of vessel dilatation and augmentation in vascular blood flow after a prespecified period of flow interruption. RHI is determined as the ratio of the post-to-pre- occlusion peripheral arterial tonometry amplitude of the tested (occluded) arm, divided by the post to-pre-occlusion ratio of the control arm. RHI values \>1.67 indicate normal endothelial function, while values ≤1.67 indicate endothelial dysfunction.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=9 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
n=19 Participants
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13
Baseline
|
2.327 ratio
Standard Error 1.118
|
1.918 ratio
Standard Error 0.587
|
1.683 ratio
Standard Error 0.379
|
1.807 ratio
Standard Error 0.501
|
|
Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13
Day 13 predose AM
|
0.282 ratio
Standard Error 0.219
|
-0.006 ratio
Standard Error 0.163
|
0.177 ratio
Standard Error 0.176
|
0.086 ratio
Standard Error 0.120
|
PRIMARY outcome
Timeframe: Baseline, Day 8, Day 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment. Participants with a baseline (BL) and postbaseline (PBL) assessment at given time point, by specific BL category \< 180 or ≥ 180 PRU.
Platelet reactivity, as measured by VerifyNow PRU assay, and presented as number of participants with \< 180 PRU or ≥ 180 PRU post-baseline (Days 8 and 14), by baseline category. The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values \< 180 units indicate impairment of platelet aggregation.
Outcome measures
| Measure |
Placebo
n=5 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay
PRU Day 8: ≥180 BL, ≥180 PBL
|
5 Participants
|
10 Participants
|
10 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay
PRU Day 14: ≥180 BL, ≥180 PBL
|
5 Participants
|
10 Participants
|
10 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay
Baseline: <180 PRU
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay
Baseline: ≥180 PRU
|
5 Participants
|
10 Participants
|
10 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay
PRU Day 8: ≥180 BL, <180 PBL
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay
PRU Day 14: ≥180 BL, <180 PBL
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 8, Day 14Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment. Participants with a baseline (BL) and postbaseline (PBL) assessment at given time point, by specific BL category (≤ 549 or \> 549 ARU).
Platelet reactivity, as measured by VerifyNow ARU assay, and presented as number of participants with ≤ 549 ARU or \> 549 ARU post-baseline (Days 8 and 14), by baseline category. Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the glycoprotein (GP)IIb/IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU.
Outcome measures
| Measure |
Placebo
n=5 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
Baseline: ≤ 549 ARU
|
2 Participants
|
5 Participants
|
6 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
Baseline: > 549 ARU
|
3 Participants
|
5 Participants
|
4 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
Day 8: ≤ 549 BL, ≤ 549 PBL
|
2 Participants
|
5 Participants
|
6 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
Day 8: ≤ 549 BL, > 549 PBL
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
Day 8: > 549 BL, ≤ 549 PBL
|
1 Participants
|
2 Participants
|
0 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
Day 8: > 549 BL, > 549 PBL
|
2 Participants
|
3 Participants
|
4 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
Day 14: ≤ 549 BL, ≤ 549 PBL
|
2 Participants
|
2 Participants
|
6 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
Day 14: ≤ 549 BL, > 549 PBL
|
0 Participants
|
3 Participants
|
0 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
Day 14: > 549 BL, ≤ 549 PBL
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
Day 14: > 549 BL, > 549 PBL
|
3 Participants
|
5 Participants
|
3 Participants
|
—
|
PRIMARY outcome
Timeframe: Study Baseline (Day 1 predose), Day 8 (predose AM), Day 14 (predose AM)Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment. Participants with a baseline (BL) and postbaseline (PBL) assessment at given time point.
The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values \<180 PRU indicate impairment of platelet aggregation.
Outcome measures
| Measure |
Placebo
n=5 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay
Study Baseline (Day 1 predose)
|
304.0 PRU
Standard Deviation 48.8
|
283.6 PRU
Standard Deviation 43.1
|
294.4 PRU
Standard Deviation 36.9
|
—
|
|
Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay
Change at Day 8
|
-9.4 PRU
Standard Deviation 47.8
|
8.2 PRU
Standard Deviation 31.4
|
-0.7 PRU
Standard Deviation 36.4
|
—
|
|
Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay
Change at Day 14
|
-4.4 PRU
Standard Deviation 38.1
|
24.4 PRU
Standard Deviation 38.2
|
8.5 PRU
Standard Deviation 24.5
|
—
|
PRIMARY outcome
Timeframe: Study Baseline (Day 1 predose), Day 8 (pre AM dose), Day 14 (pre AM dose)Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment. Participants with a baseline (BL) and postbaseline (PBL) assessment at given time point.
Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the GPIIb IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU.
Outcome measures
| Measure |
Placebo
n=5 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay
Study Baseline (Day 1 predose)
|
571.4 ARU
Standard Deviation 82.5
|
557.4 ARU
Standard Deviation 76.3
|
524.6 ARU
Standard Deviation 89.5
|
—
|
|
Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay
Change at Day 8
|
-8.0 ARU
Standard Deviation 58.5
|
-16.2 ARU
Standard Deviation 50.9
|
18.7 ARU
Standard Deviation 29.4
|
—
|
|
Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay
Change at Day 14
|
10.2 ARU
Standard Deviation 19.8
|
30.2 ARU
Standard Deviation 34.9
|
-11.7 ARU
Standard Deviation 34.9
|
—
|
PRIMARY outcome
Timeframe: Study baseline (defined as the last non-missing assessment before the first administration of study drug), Day 8, pre-AM dose, Day 15Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment. Participants with a baseline (BL) and postbaseline (PBL) assessment at given time point who did not use concomitant insulin.
Blood samples were taken for fasting glucose and insulin levels. From these results, insulin resistance was then estimated using the updated homeostasis model assessment method for insulin resistance (HOMA-IR) computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Typically a cutoff of HOMA-IR for identifying those with insulin resistance is 2.5.
Outcome measures
| Measure |
Placebo
n=4 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=5 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=7 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
n=12 Participants
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin
Study Baseline (Day 1 predose)
|
7.350 percent change
Standard Error 5.236
|
6.646 percent change
Standard Error 3.403
|
7.187 percent change
Standard Error 5.684
|
6.962 percent change
Standard Error 4.681
|
|
Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin
Day 8
|
-4.284 percent change
Standard Error 20.823
|
-27.473 percent change
Standard Error 18.639
|
-18.318 percent change
Standard Error 15.735
|
-22.895 percent change
Standard Error 12.191
|
|
Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin
Day 15
|
-12.839 percent change
Standard Error 12.565
|
-38.228 percent change
Standard Error 11.263
|
-34.015 percent change
Standard Error 10.270
|
-36.121 percent change
Standard Error 7.609
|
PRIMARY outcome
Timeframe: Days 1 and 7 (AM): 1, 3, and 6 hours postdosePopulation: Pharmacokinetic (PK) Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
Equivalent to AUC from time 0 to the last measurable concentration (AUClast), with time of last measurable concentration (Tlast)=12 hours for BID dosing and Tlast=24 hours for QD dosing.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7
Day 1
|
362 h*ng/mL
Standard Deviation 88
|
339 h*ng/mL
Standard Deviation 134
|
1190 h*ng/mL
Standard Deviation 499
|
—
|
|
IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7
Day 7
|
795 h*ng/mL
Standard Deviation 186
|
—
|
2200 h*ng/mL
Standard Deviation 591
|
—
|
PRIMARY outcome
Timeframe: Days 1 and 7 (AM): 1, 3, and 6 hours postdosePopulation: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7
Day 1
|
73.8 ng/mL
Standard Deviation 18.9
|
47.8 ng/mL
Standard Deviation 22.2
|
181 ng/mL
Standard Deviation 107
|
—
|
|
IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7
Day 7
|
117 ng/mL
Standard Deviation 32.6
|
—
|
242 ng/mL
Standard Deviation 80.0
|
—
|
PRIMARY outcome
Timeframe: Days 1 and 7 (AM): 1, 3, and 6 hours postdosePopulation: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7
Day 1
|
1.0 hours
Interval 1.0 to 3.0
|
3.0 hours
Interval 3.0 to 11.9
|
2.0 hours
Interval 1.0 to 6.0
|
—
|
|
IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7
Day 7
|
1.0 hours
Interval 1.0 to 3.0
|
—
|
1.0 hours
Interval 1.0 to 6.0
|
—
|
PRIMARY outcome
Timeframe: Days 1 and 7: predose; Day 2 (BID AM): predose; Day 6 (BID PM/QD): predosePopulation: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7
Day 1
|
11.6 ng/mL
Standard Deviation 4.29
|
19.6 ng/mL
Standard Deviation 5.04
|
15.6 ng/mL
Standard Deviation 5.24
|
—
|
|
IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7
Day 2
|
21.0 ng/mL
Standard Deviation 5.97
|
—
|
—
|
—
|
|
IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7
Day 6
|
—
|
48.4 ng/mL
Standard Deviation 10.1
|
53.7 ng/mL
Standard Deviation 14.5
|
—
|
|
IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7
Day 7
|
45.6 ng/mL
Standard Deviation 14.5
|
52.4 ng/mL
Standard Deviation 12.8
|
57.2 ng/mL
Standard Deviation 14.9
|
—
|
PRIMARY outcome
Timeframe: Day 8 and 14: 1, 3, 6h (± 5 min) postdosePopulation: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Plasma Concentration (AUClast) on Days 8 and 14
Day 8
|
1210 h*mg/mL
Standard Deviation 264
|
1540 h*mg/mL
Standard Deviation 482
|
—
|
—
|
|
IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Plasma Concentration (AUClast) on Days 8 and 14
Day 14
|
17100 h*mg/mL
Standard Deviation 6980
|
23600 h*mg/mL
Standard Deviation 8950
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 14: 1, 3, 6h (± 5 min) postdosePopulation: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
IW-1973 Pharmacokinetics: AUCtau on Day 14
|
2080 ng/mL
Standard Deviation 442
|
2910 ng/mL
Standard Deviation 770
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 8 and 14: 1, 3, 6h (± 5 min) postdosePopulation: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
IW-1973 Pharmacokinetics: Tmax on Days 8 and 14
Day 8
|
1.0 hours
Interval 1.0 to 3.0
|
1.0 hours
Interval 1.0 to 6.2
|
—
|
—
|
|
IW-1973 Pharmacokinetics: Tmax on Days 8 and 14
Day 14
|
1.0 hours
Interval 1.0 to 3.0
|
3.0 hours
Interval 1.0 to 6.0
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 8 and 14: 1, 3, 6h (± 5 min) postdosePopulation: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
IW-1973 Pharmacokinetics: Cmax on Days 8 and 14
Day 8
|
198 ng/mL
Standard Deviation 56.8
|
229 ng/mL
Standard Deviation 90.6
|
—
|
—
|
|
IW-1973 Pharmacokinetics: Cmax on Days 8 and 14
Day 14
|
181 ng/mL
Standard Deviation 46.8
|
250 ng/mL
Standard Deviation 139
|
—
|
—
|
PRIMARY outcome
Timeframe: Days 13 and 14: predosePopulation: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14
Day 14
|
65.7 ng/mL
Standard Deviation 23.0
|
90.7 ng/mL
Standard Deviation 26.2
|
—
|
—
|
|
IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14
Day 13
|
56.8 ng/mL
Standard Deviation 19.5
|
82.4 ng/mL
Standard Deviation 22.7
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 14: 1, 3, 6h (± 5 min) postdosePopulation: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
IW-1973 Pharmacokinetics: Apparent Total Body Clearance (CL/F) on Day 14
|
20.0 L/h
Standard Deviation 4.34
|
14.7 L/h
Standard Deviation 3.89
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 14: 1, 3, 6h (± 5 min) postdosePopulation: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
IW-1973 Pharmacokinetics: Apparent Volume of Distribution During the Terminal Phase (Vz/F) on Day 14
|
5570 L
Standard Deviation 1530
|
3880 L
Standard Deviation 1370
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 14 (final dose) time points 12 hours, 24 hours, 7 days after final dose (Day 21), and 28 days after final dose(Day 42)Population: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
Outcome measures
| Measure |
Placebo
n=10 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
IW-1973 Pharmacokinetics: Apparent Terminal Elimination Phase Half-Life (t1/2)
|
197 hours
Standard Deviation 57.4
|
183 hours
Standard Deviation 43.4
|
—
|
—
|
PRIMARY outcome
Timeframe: From first dose of study drug to End of Trial Visit (42 [± 3] days)Population: Safety Population: participants who received at least 1 dose of study drug.
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. AEs of clinical interest (AECI) included those related to bleeding and to hypotension. Study drug causality as assessed by the Investigator who was blinded to study drug assignment.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
TEAE
|
5 participants
|
6 participants
|
8 participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
SAE
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
Severe TEAE
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
Moderate TEAE
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
Mild TEAE
|
5 participants
|
6 participants
|
8 participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
TEAE Considered Study Drug Related
|
1 participants
|
3 participants
|
6 participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
TEAE Considered Not Study Drug Related
|
4 participants
|
6 participants
|
7 participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
TEAE Resulting in Study Discontinuation
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
TEAE Resulting in Death
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
AECI Related to Bleeding
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
AECI Related to Hypotension
|
1 participants
|
1 participants
|
0 participants
|
—
|
PRIMARY outcome
Timeframe: From first dose of study drug to End of Trial Visit (42 [± 3] days)Population: Safety Population: participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Meaningful Postbaseline Laboratory Test Results
|
0 participants
|
1 participants
|
1 participants
|
—
|
PRIMARY outcome
Timeframe: From first dose of study drug to End of Trial Visit (42 [± 3] days)Population: Safety Population: participants who received at least 1 dose of study drug.
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 heart rate (SHR): ≥ 110 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 heart rate (StHR): ≥ 110 bpm and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm. Orthostatic systolic blood pressure (SBP): ↓ \> 20 mmHg from supine to standing. Orthostatic diastolic blood pressure (DBP): ↓ \> 15 mmHg from supine to standing. Orthostatic HR: ↓ \> 30 bpm from supine to standing.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
SSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
SSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
SDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
SDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg
|
0 participants
|
2 participants
|
0 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
SHR: ≥ 110 bpm and ↑ from BL ≥ 20 bpm
|
1 participants
|
2 participants
|
0 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
SHR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm
|
1 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
StSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
StSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg
|
0 participants
|
2 participants
|
0 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
StDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
StHR: ≥ 120 bpm and ↑ from BL ≥ 25 bpm
|
0 participants
|
1 participants
|
1 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
Orthostatic SBP: ↓ > 20 mmHg, Supine to Standing
|
2 participants
|
4 participants
|
3 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
Orthostatic DBP: ↓ > 15 mmHg, Supine to Standing
|
1 participants
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
StDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
StHR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
Orthostatic HR: ↑ > 30 bpm, Supine to Standing
|
2 participants
|
2 participants
|
1 participants
|
—
|
PRIMARY outcome
Timeframe: Post-randomization to End of Trial Visit (42 [± 3] days)Population: Safety Population: participants who received at least 1 dose of study drug.
Physical examinations included examination and assessment of the following: general appearance, lymph nodes, skin, cardiovascular system, head, eyes, ears, nose, and throat, central nervous system, respiratory system, neck, peripheral nervous system, abdomen/liver/spleen, musculoskeletal system.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Post-Randomization Physical Examination Findings
|
0 participants
|
0 participants
|
0 participants
|
—
|
PRIMARY outcome
Timeframe: From first dose of study drug to End of Trial Visit (42 [± 3] days)Population: Safety Population: participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results
|
0 participants
|
0 participants
|
0 participants
|
—
|
PRIMARY outcome
Timeframe: Study Baseline, Day 15/Discharge, Day 42/End of TrialPopulation: Safety Population: participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
Placebo
n=6 Participants
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 Participants
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 Participants
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
IW-1973 40 mg Total Daily Dose (Overall)
IW-1973 40 mg BID/QD:
IW-973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7. IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
IW-1973 40 mg QD/QD:
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|---|
|
Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR)
Study Baseline
|
103.045 mL/min/1.73m^2
Standard Deviation 7.542
|
89.014 mL/min/1.73m^2
Standard Deviation 19.729
|
80.373 mL/min/1.73m^2
Standard Deviation 19.716
|
—
|
|
Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR)
Day 15/Discharge
|
0.158 mL/min/1.73m^2
Standard Deviation 4.050
|
-2.232 mL/min/1.73m^2
Standard Deviation 7.275
|
1.663 mL/min/1.73m^2
Standard Deviation 5.803
|
—
|
|
Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR)
Day 42/End of Trial
|
-3.727 mL/min/1.73m^2
Standard Deviation 10.262
|
-8.905 mL/min/1.73m^2
Standard Deviation 4.293
|
-5.587 mL/min/1.73m^2
Standard Deviation 6.196
|
—
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
IW-1973 40 mg BID/QD
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
IW-1973 40 mg QD/QD
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=6 participants at risk
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 participants at risk
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 participants at risk
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
Other adverse events
| Measure |
Placebo
n=6 participants at risk
Placebo oral tablet taken in AM and in PM on Days 1-14.
|
IW-1973 40 mg BID/QD
n=10 participants at risk
IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14.
|
IW-1973 40 mg QD/QD
n=10 participants at risk
IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Eye disorders
Eye irritation
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
20.0%
2/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
30.0%
3/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
30.0%
3/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
20.0%
2/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Gastrointestinal disorders
Gastrointestinal sounds abnormal
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
General disorders
Injection site haemorrhage
|
50.0%
3/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
General disorders
Injection site injury
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Infections and infestations
Paronychia
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
33.3%
2/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
20.0%
2/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
30.0%
3/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Metabolism and nutrition disorders
Pseudohypoglycaemia
|
16.7%
1/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Musculoskeletal and connective tissue disorders
Limb discomfort
|
16.7%
1/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Nervous system disorders
Headache
|
33.3%
2/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
20.0%
2/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
30.0%
3/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Nervous system disorders
Dizziness
|
16.7%
1/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Nervous system disorders
Tremor
|
16.7%
1/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Renal and urinary disorders
Nephrolithiasis
|
16.7%
1/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Renal and urinary disorders
Nocturia
|
16.7%
1/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/6 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
10.0%
1/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
0.00%
0/10 • From first dose of study drug to End of Trial Visit (42 [± 3] days)
|
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