| Outcome Measures: |
Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to TEAEs, 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., From first dose of study drug through end of trial (Day 46 [±3 days])|Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19), Study baseline is defined as the Day -1 assessment., Baseline, Day 19|Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32), Study baseline is defined as the Day -1 assessment., Baseline, Day 32|Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase at Discharge Day (Day 19), Study baseline is defined as the Day -1 assessment., Baseline, Day 19|Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in GGT and Lactate Dehydrogenase at Follow-Up (Day 32), Study baseline is defined as the Day -1 assessment., Baseline, Day 32|Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Discharge Day (Day 19), Study baseline is defined as the Day -1 assessment., Baseline, Day 19|Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Follow-Up (Day 32), Study baseline is defined as the Day -1 assessment., Baseline, Day 32|Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Discharge Day (Day 19), Study baseline is defined as the Day -1 assessment., Baseline, Day 19|Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Follow-Up (Day 32), Study baseline is defined as the Day -1 assessment., Baseline, Day 32|Change From Time-Matched Baseline in Fasting Blood Glucose on Day 2 of Each Dose Cycle, Time-matched baseline is defined as the corresponding assessment on Day 2 of the placebo cycle. Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data., Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)|Change From Time-Matched Baseline in Serum Insulin on Day 2 of Each Dose Cycle, Time-matched baseline is defined as the corresponding assessment on Day 2 of the placebo cycle. Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data., Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)|Number of Participants With Notable Changes in Post Baseline Vital Signs Values, Supine systolic blood pressure (SSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Supine Diastolic Blood Pressure (SDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Supine pulse rate (SPR): ≥ 110 beats per minute (bpm) and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm. Standing systolic blood pressure (StSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Standing Diastolic Blood Pressure (StDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Standing pulse rate (StPR): ≥ 110 beats per minute (bpm) and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm., Up to Day 32|Number of Participants With Notable Post Baseline Orthostatic Vital Signs Values, Systolic blood pressure (SBP): Decrease of \> 20 mmHg from supine to standing Diastolic blood pressure (DBP): Decrease of \> 10 mmHg from supine to standing Pulse rate (PR): Increase of \> 20 bpm from supine to standing., Up to Day 32|Change From Baseline Over Time in Respiratory Rate, Baseline, Day 19, Day 32|Change From Baseline Over Time in Temperature, Baseline, Day 19, Day 32|Change From Baseline Over Time in Weight, Baseline, Day 19, Day 32|Number of Participants With Clinically Significant Findings or Shifts in Baseline in Electrocardiograms (ECGs), Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19|Number of Participants With Clinically Significant Findings or Shifts in Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF), Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19|Change From Study Baseline Over Time in Supine Pulse, Study baseline is defined as the Day -1 assessment., Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h|Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse, Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h|Change From Study Baseline Over Time in Supine Systolic Blood Pressure, Study baseline is defined as the Day -1 assessment., Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h|Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure, Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h|Change From Study Baseline Over Time in Supine Diastolic Blood Pressure, Study baseline is defined as the Day -1 assessment., Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h|Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure, Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h|Orthostatic Pulse Over Time, An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement., Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h|Orthostatic Systolic Blood Pressure Over Time, An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement., Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h|Orthostatic Diastolic Blood Pressure Over Time, An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement., Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h|Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure, Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs|Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure, Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs|Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure, Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 2|Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure, Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs|Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure, Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs|Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Diastolic Blood Pressure, Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 2|Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure, Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs|Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure, Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs|Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Mean Arterial Pressure, Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 2|Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse, Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs|Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse, Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs|Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Pulse, Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data., Time-Matched Baseline (Placebo Cycle); Cycle Day 2|Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Pulse, Follow-up Visit Day 32 (± 2 days)|Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Systolic Blood Pressure, Follow-up Visit Day 32 (± 2 days)|Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Diastolic Blood Pressure, Follow-up Visit Day 32 (± 2 days)|Change From Study Baseline Over Time in Endothelial Function: Reactive Hyperemia Index (RHI), Study baseline is defined as the Day -1 assessment. Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction., Study Baseline; Cycle Day 3: 0 h, 4 h, 12 h|Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI, Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction. Baseline is designated per protocol as Day 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 3 of each IW-1973 dose at given time point are presented as the second row of data., Time-matched Baseline (Placebo Cycle); Cycle Day 3: 0 h, 4 h, 12 h|Change From Pre- to Post-Nitroglycerin Dose Assessment in Endothelial Function: RHI, Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction., Follow-up Visit Day 32 (± 2 days)|Change From Time-Matched Baseline (Placebo Cycle) in Platelet Function Assessments: Collagen/Epinephrine Time to Aggregation, Time-matched baseline is defined as the corresponding assessment on Day 1 of the placebo cycle. Platelet function assessment used the PFA-100® instrument to evaluate collagen/epinephrine time to aggregation. Baseline is designated per protocol as Day 1 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 of each IW-1973 dose at given time point are presented as the second row of data., Time-Matched Baseline (Placebo Cycle), Cycle Day 1, 0 h, Cycle Day 1, 4 h |
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