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A Phase 2 Trial of IW-1973, A Stimulator of Soluble Guanylate Cyclase (sGC), in Patients With Stable Type 2 Diabetes and Hypertension

Sponsor
Cyclerion Therapeutics (Industry)
Overall Status
Completed
CT.gov ID
NCT02906579
Collaborator
(none)
11
Enrollment
1
Location
1
Arm
6.5
Actual Duration (Months)
1.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the impact of escalating doses of IW-1973 on endothelial function [using EndoPAT to measure fingertip small vessel pulse volume], blood pressure (BP), and heart rate.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
11 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Phase 2a Trial to Evaluate the Effect of Escalating Doses of IW-1973 on Tolerability, Endothelial Function, and Hemodynamics in Patients With Stable Type 2 Diabetes and Hypertension
Actual Study Start Date :
Sep 1, 2016
Actual Primary Completion Date :
Mar 17, 2017
Actual Study Completion Date :
Mar 17, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: IW-1973

Placebo taken once daily Day 1-Day 3; 10 mg IW-1973 take once daily Day 4-Day 6; 20 mg IW-1973 taken once daily Day 7-Day 9; 30 mg IW-1973 taken once daily Day 10-Day 12; 40 mg IW-1973 taken once daily Day 13-Day 15; 50 mg IW-1973 taken once daily Day 16-Day 18

Drug: Matching Placebo

Drug: IW-1973

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to TEAEs [From first dose of study drug through end of trial (Day 46 [±3 days])]

    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.

  2. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19) [Baseline, Day 19]

    Study baseline is defined as the Day -1 assessment.

  3. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32) [Baseline, Day 32]

    Study baseline is defined as the Day -1 assessment.

  4. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase at Discharge Day (Day 19) [Baseline, Day 19]

    Study baseline is defined as the Day -1 assessment.

  5. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in GGT and Lactate Dehydrogenase at Follow-Up (Day 32) [Baseline, Day 32]

    Study baseline is defined as the Day -1 assessment.

  6. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Discharge Day (Day 19) [Baseline, Day 19]

    Study baseline is defined as the Day -1 assessment.

  7. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Follow-Up (Day 32) [Baseline, Day 32]

    Study baseline is defined as the Day -1 assessment.

  8. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Discharge Day (Day 19) [Baseline, Day 19]

    Study baseline is defined as the Day -1 assessment.

  9. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Follow-Up (Day 32) [Baseline, Day 32]

    Study baseline is defined as the Day -1 assessment.

  10. Change From Time-Matched Baseline in Fasting Blood Glucose on Day 2 of Each Dose Cycle [Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)]

    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.

  11. Change From Time-Matched Baseline in Serum Insulin on Day 2 of Each Dose Cycle [Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)]

    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.

  12. Number of Participants With Notable Changes in Post Baseline Vital Signs Values [Up to Day 32]

    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.

  13. Number of Participants With Notable Post Baseline Orthostatic Vital Signs Values [Up to Day 32]

    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.

  14. Change From Baseline Over Time in Respiratory Rate [Baseline, Day 19, Day 32]

  15. Change From Baseline Over Time in Temperature [Baseline, Day 19, Day 32]

  16. Change From Baseline Over Time in Weight [Baseline, Day 19, Day 32]

  17. 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]

  18. 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]

  19. Change From Study Baseline Over Time in Supine Pulse [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]

    Study baseline is defined as the Day -1 assessment.

  20. Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse [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]

    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.

  21. Change From Study Baseline Over Time in Supine Systolic Blood Pressure [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]

    Study baseline is defined as the Day -1 assessment.

  22. Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure [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]

    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.

  23. Change From Study Baseline Over Time in Supine Diastolic Blood Pressure [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]

    Study baseline is defined as the Day -1 assessment.

  24. Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure [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]

    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.

  25. Orthostatic Pulse Over Time [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]

    An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.

  26. Orthostatic Systolic Blood Pressure Over Time [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]

    An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.

  27. Orthostatic Diastolic Blood Pressure Over Time [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]

    An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.

  28. Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure [Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs]

    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.

  29. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure [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]

    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.

  30. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure [Time-Matched Baseline (Placebo Cycle); Cycle Day 2]

    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.

  31. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure [Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs]

    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.

  32. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure [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]

    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.

  33. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Diastolic Blood Pressure [Time-Matched Baseline (Placebo Cycle); Cycle Day 2]

    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.

  34. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure [Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs]

    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.

  35. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure [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]

    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.

  36. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Mean Arterial Pressure [Time-Matched Baseline (Placebo Cycle); Cycle Day 2]

    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.

  37. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse [Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs]

    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.

  38. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse [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]

    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.

  39. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Pulse [Time-Matched Baseline (Placebo Cycle); Cycle Day 2]

    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.

  40. Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Pulse [Follow-up Visit Day 32 (± 2 days)]

  41. Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Systolic Blood Pressure [Follow-up Visit Day 32 (± 2 days)]

  42. Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Diastolic Blood Pressure [Follow-up Visit Day 32 (± 2 days)]

  43. Change From Study Baseline Over Time in Endothelial Function: Reactive Hyperemia Index (RHI) [Study Baseline; Cycle Day 3: 0 h, 4 h, 12 h]

    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.

  44. Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI [Time-matched Baseline (Placebo Cycle); Cycle Day 3: 0 h, 4 h, 12 h]

    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.

  45. Change From Pre- to Post-Nitroglycerin Dose Assessment in Endothelial Function: RHI [Follow-up Visit Day 32 (± 2 days)]

    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.

  46. Change From Time-Matched Baseline (Placebo Cycle) in Platelet Function Assessments: Collagen/Epinephrine Time to Aggregation [Time-Matched Baseline (Placebo Cycle), Cycle Day 1, 0 h, Cycle Day 1, 4 h]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
30 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Patient is ambulatory male or female

  • Patient's body mass index score is >20 and <40 kg/m2 at the Screening Visit

  • Women of childbearing potential must have a negative pregnancy test at the time of check-in and must agree to use double-barrier contraception throughout the duration of the study

  • Patient's health is stable with no clinically significant findings on a physical examination

  • Patient has type 2 (ie adult onset) diabetes mellitus diagnosed by a physician or nurse practitioner > 6 months before the Screening Visit, and an entry HbA1c that does not mandate prompt intervention for improved control

  • Patient has hypertension diagnosed by a physician or nurse practitioner > 6 months before the Screening Visit and BP within the protocol's acceptable range

  • Patients must be on a stable regimen for glycemic control, and a stable regimen for hypertension control that includes an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB)

  • Patient has abnormal endothelial function measured by the EndoPAT

  • Other inclusion criteria per protocol

Exclusion Criteria:

  • Patient has a clinically significant active or unstable medical condition that, in the opinion of the Investigator, would preclude trial participation

  • Patient is on medication(s) that when co-administered with a soluble guanylate cyclase (sGC) stimulator, could increase the risk of hypotension

  • Patient has evidence of severe or active end-organ damage attributable to diabetes

  • Patient has severe renal insufficiency, has undergone renal transplantation, or has planned renal transplantation

  • Other exclusion criteria per protocol

Contacts and Locations

Locations

Site City State Country Postal Code
1 ICON Early Phase Unit San Antonio Texas United States 78209

Sponsors and Collaborators

  • Cyclerion Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Cyclerion Therapeutics
ClinicalTrials.gov Identifier:
NCT02906579
Other Study ID Numbers:
  • C1973-201
First Posted:
Sep 20, 2016
Last Update Posted:
Apr 16, 2020
Last Verified:
Apr 1, 2020
Additional relevant MeSH terms:
Hypertension
Diabetes Mellitus
Diabetes Mellitus, Type 2
Praliciguat

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Period Title: Overall Study
STARTED 11
Completed Cycle 1 (Placebo) 11
Completed Cycle 2 (10 mg IW-1973) 11
Completed Cycle 3 (20 mg IW-1973) 11
Completed Cycle 4 (30 mg IW-1973) 10
Completed Cycle 5 (40 mg IW-1973) 9
Completed Cycle 6 (50 mg IW-1973) 9
COMPLETED 9
NOT COMPLETED 2

Baseline Characteristics

Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Overall Participants 11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
56.6
(6.8)
Sex: Female, Male (Count of Participants)
Female
4
36.4%
Male
7
63.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
5
45.5%
Not Hispanic or Latino
6
54.5%
Unknown or Not Reported
0
0%
Race/Ethnicity, Customized (Count of Participants)
White
6
54.5%
Black or African American
5
45.5%
Study Baseline: Supine systolic blood pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]
136.3
(12.9)
Study Baseline: Supine diastolic blood pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]
80.4
(5.9)
Study Baseline: Pulse (beats per minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats per minute]
72.0
(15.9)
Study Baseline: Cholesterol, Glucose, HDL-C, LDL-C, Triglycerides (mg/dL) [Mean (Standard Deviation) ]
Cholesterol
185.0
(44.9)
Glucose
143.27
(34.34)
High-density lipoprotein cholesterol (HDL-C)
50.27
(14.11)
Low-density lipoprotein cholesterol (LDL-C)
107.45
(36.74)
Triglycerides
137.73
(54.23)
Study Baseline: Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (U/L) [Mean (Standard Deviation) ]
GGT
36.2
(28.4)
Lactate Dehydrogenase
163.1
(30.7)
Study Baseline: Hemoglobin A1c (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]
7.67
(1.33)
Study Baseline: Insulin (μIU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [μIU/mL]
17.50
(12.17)
Study Baseline: Respiratory Rate (breaths/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [breaths/min]
16.4
(2.2)
Study Baseline: Temperature (degrees celcius) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [degrees celcius]
36.68
(0.21)
Study Baseline: Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]
91.08
(11.58)

Outcome Measures

1. Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to TEAEs
Description 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.
Time Frame From first dose of study drug through end of trial (Day 46 [±3 days])

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description Placebo taken once daily Day 1-Day 3 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 11 10 9 9
≥1 TEAE
3
27.3%
3
NaN
2
NaN
4
NaN
3
NaN
2
NaN
SAE
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
Deaths
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
Discontinuations (DCs) due to AEs
0
0%
0
NaN
1
NaN
0
NaN
0
NaN
0
NaN
DCs Due to Trough Blood Pressure Decline
0
0%
0
NaN
1
NaN
1
NaN
0
NaN
0
NaN
2. Primary Outcome
Title Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)
Description Study baseline is defined as the Day -1 assessment.
Time Frame Baseline, Day 19

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Cholesterol: Day 19/Discharge
141.7
(39.6)
Cholesterol: Change at Day 19/Discharge
-43.3
(35.1)
Glucose: Day 19/Discharge
116.82
(25.43)
Glucose: Change at Day 19/Discharge
-26.45
(25.25)
HDL-C: Day 19/Discharge
44.36
(10.74)
HDL-C: Change at Day 19/Discharge
-5.91
(7.73)
LDL-C: Day 19/Discharge
73.09
(34.69)
LDL-C: Change at Day 19/Discharge
-34.36
(28.88)
Triglycerides: Day 19/Discharge
121.73
(46.10)
Triglycerides: Change at Day 19/Discharge
-16.00
(42.45)
3. Primary Outcome
Title Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)
Description Study baseline is defined as the Day -1 assessment.
Time Frame Baseline, Day 32

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Cholesterol: Day 32/Follow-Up
183.1
(48.6)
Cholesterol: Change at Day 32/Follow-Up
-1.9
(27.1)
Glucose: Day 32/Follow-Up
154.27
(48.54)
Glucose: Change at Day 32/Follow-Up
11.00
(41.47)
HDL-C: Day 32/Follow-Up
48.18
(10.32)
HDL-C: Change at Day 32/Follow-Up
-2.09
(6.88)
LDL-C: Day 32/Follow-Up
107.27
(42.11)
LDL-C: Change at Day 32/Follow-Up
-0.18
(23.84)
Triglycerides: Day 32/Follow-Up
138.09
(46.26)
Triglycerides: Change at Day 32/Follow-Up
0.36
(52.94)
4. Primary Outcome
Title Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase at Discharge Day (Day 19)
Description Study baseline is defined as the Day -1 assessment.
Time Frame Baseline, Day 19

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
GGT: Day 19/Discharge
28.3
(17.2)
GGT: Change at Day 19/Discharge
-7.9
(15.9)
Lactate Dehydrogenase: Day 19/Discharge
135.7
(18.2)
Lactate Dehydrogenase: Change at Day 19/Discharge
-27.4
(21.2)
5. Primary Outcome
Title Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in GGT and Lactate Dehydrogenase at Follow-Up (Day 32)
Description Study baseline is defined as the Day -1 assessment.
Time Frame Baseline, Day 32

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
GGT: Day 32/Follow-Up
53.6
(83.9)
GGT: Change at Day 32/Follow-Up
17.5
(67.8)
Lactate Dehydrogenase: Day 32/Follow-Up
171.6
(55.2)
Lactate Dehydrogenase: Change at Day 32/Follow-Up
8.5
(46.4)
6. Primary Outcome
Title Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Discharge Day (Day 19)
Description Study baseline is defined as the Day -1 assessment.
Time Frame Baseline, Day 19

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Discharge Day (Day 19)
7.27
(1.53)
Change at Discharge Day (Day 19)
-0.40
(0.54)
7. Primary Outcome
Title Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Follow-Up (Day 32)
Description Study baseline is defined as the Day -1 assessment.
Time Frame Baseline, Day 32

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Follow-Up (Day 32)
7.54
(1.49)
Change at Follow-Up (Day 32)
-0.14
(0.49)
8. Primary Outcome
Title Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Discharge Day (Day 19)
Description Study baseline is defined as the Day -1 assessment.
Time Frame Baseline, Day 19

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Discharge Day (Day 19)
17.45
(14.20)
Change at Discharge Day (Day 19)
-0.05
(5.31)
9. Primary Outcome
Title Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Follow-Up (Day 32)
Description Study baseline is defined as the Day -1 assessment.
Time Frame Baseline, Day 32

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Follow-Up (Day 32)
23.81
(18.81)
Change at Follow-Up (Day 32)
6.31
(11.18)
10. Primary Outcome
Title Change From Time-Matched Baseline in Fasting Blood Glucose on Day 2 of Each Dose Cycle
Description 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 Frame Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)

Outcome Measure Data

Analysis Population Description
Pharmacodynamic (PD) Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 10 9 9
Time-Matched Baseline
142.3
(32.6)
142.3
(32.6)
144.1
(33.8)
147.7
(33.8)
147.7
(33.8)
Cycle Day 2 Change
-12.0
(10.3)
-13.4
(9.9)
-21.1
(16.0)
-24.3
(16.9)
-25.3
(15.9)
11. Primary Outcome
Title Change From Time-Matched Baseline in Serum Insulin on Day 2 of Each Dose Cycle
Description 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 Frame Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 10 9 9
Time-Matched Baseline
17.35
(10.70)
17.35
(10.70)
17.37
(11.28)
14.32
(6.21)
14.32
(6.21)
Cycle Day 2 Change
0.20
(5.04)
-0.40
(6.26)
-2.61
(3.11)
-2.49
(5.65)
-2.70
(4.20)
12. Primary Outcome
Title Number of Participants With Notable Changes in Post Baseline Vital Signs Values
Description 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.
Time Frame Up to Day 32

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment
Arm/Group Title Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description Placebo taken once daily Day 1-Day 3 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 11 10 9 9
SSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
SSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg
0
0%
0
NaN
1
NaN
2
NaN
0
NaN
0
NaN
SDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
SDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
SPR: ≥ 110 bpm and ↑ from BL
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
SPR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
StSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
StSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg
0
0%
0
NaN
0
NaN
0
NaN
1
NaN
0
NaN
StDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
StDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
StPR: ≥ 120 bpm and ↑ from BL
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
StPR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
13. Primary Outcome
Title Number of Participants With Notable Post Baseline Orthostatic Vital Signs Values
Description 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.
Time Frame Up to Day 32

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment
Arm/Group Title Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description Placebo taken once daily Day 1-Day 3 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 11 10 9 9
SBP: Decrease of > 20 mmHg, supine to standing
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
DBP: Decrease of > 10 mmHg from supine to standin
0
0%
0
NaN
1
NaN
0
NaN
1
NaN
0
NaN
PR: Increase of > 20 bpm from supine to standing
3
27.3%
4
NaN
3
NaN
5
NaN
3
NaN
3
NaN
14. Primary Outcome
Title Change From Baseline Over Time in Respiratory Rate
Description
Time Frame Baseline, Day 19, Day 32

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Change at Day 19/Discharge
-0.7
(1.8)
Change at Day 32/Follow-Up
-1.5
(2.7)
15. Primary Outcome
Title Change From Baseline Over Time in Temperature
Description
Time Frame Baseline, Day 19, Day 32

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Change at Day 19/Discharge
0.12
(0.19)
Change at Day 32/Follow-Up
-0.03
(0.20)
16. Primary Outcome
Title Change From Baseline Over Time in Weight
Description
Time Frame Baseline, Day 19, Day 32

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Change at Day 19/Discharge
-3.47
(2.16)
Change at Day 32/Follow-Up
-1.40
(1.61)
17. Primary Outcome
Title Number of Participants With Clinically Significant Findings or Shifts in Baseline in Electrocardiograms (ECGs)
Description
Time Frame Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Count of Participants [Participants]
0
0%
18. Primary Outcome
Title Number of Participants With Clinically Significant Findings or Shifts in Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF)
Description
Time Frame Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.
Arm/Group Title Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description Placebo taken once daily Day 1-Day 3 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 11 10 9 9
Count of Participants [Participants]
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
19. Primary Outcome
Title Change From Study Baseline Over Time in Supine Pulse
Description Study baseline is defined as the Day -1 assessment.
Time Frame 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

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description Placebo taken once daily Day 1-Day 3 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 11 10 9 9
Study Baseline
72.0
(15.9)
72.0
(15.9)
72.0
(15.9)
72.7
(16.6)
73.2
(17.5)
73.2
(17.5)
Change at Cycle Day 1, 0 h
-5.5
(7.6)
-6.5
(11.6)
-5.8
(11.1)
-7.2
(11.0)
-4.9
(12.1)
-6.3
(13.7)
Change at Cycle Day 1, 1 h
-0.1
(8.7)
-1.9
(9.8)
1.7
(12.7)
5.7
(12.7)
1.0
(9.4)
4.8
(12.1)
Change at Cycle Day 1, 2 h
-1.8
(7.6)
3.4
(8.9)
6.3
(11.7)
11.9
(14.1)
13.9
(10.9)
9.0
(12.1)
Change at Cycle Day 1, 4 h
-3.5
(9.4)
-2.2
(10.7)
1.7
(9.5)
0.7
(10.6)
3.7
(7.5)
0.2
(8.8)
Change at Cycle Day 1, 8 h
-3.2
(9.7)
2.1
(12.3)
0.8
(10.2)
-1.4
(9.3)
-1.7
(11.7)
-0.2
(8.9)
Change at Cycle Day 1, 12 h
-2.3
(8.4)
4.1
(10.4)
2.9
(9.6)
0
(9.4)
3.2
(12.9)
0.8
(10.2)
Change at Cycle Day 3, 0 h
-4.1
(11.7)
-6.2
(10.7)
-5.1
(11.2)
-5.4
(10.8)
-6.8
(12.2)
-6.3
(11.4)
Change at Cycle Day 3, 1 h
-1.8
(9.3)
3.9
(11.9)
5.5
(11.7)
6.1
(8.4)
8.8
(15.2)
10.0
(13.2)
Change at Cycle Day 3, 2 h
2.0
(9.1)
4.5
(11.3)
7.2
(8.9)
9.1
(10.7)
11.1
(12.6)
11.6
(13.1)
Change at Cycle Day 3, 8 h
-1.0
(11.2)
0.6
(9.3)
-1.6
(11.7)
-1.2
(7.8)
-0.3
(11.4)
4.2
(14.8)
20. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
Description 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 Frame 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

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 10 9 9
Time Matched Baseline (Cycle Day 1, 0 h)
66.5
(10.8)
66.5
(10.8)
66.7
(11.3)
67.0
(12.0)
67.0
(12.0)
Change at Cycle Day 1, 0 h
-1.1
(5.5)
-0.4
(5.2)
-1.2
(5.7)
1.3
(7.0)
-0.1
(8.4)
Time Matched Baseline (Cycle Day 1, 1 h)
71.9
(12.6)
71.9
(12.6)
72.6
(13.0)
73.4
(13.5)
73.4
(13.5)
Change at Cycle Day 1, 1 h
-1.8
(3.2)
1.8
(5.0)
5.8
(4.7)
0.8
(4.5)
4.6
(4.3)
Time Matched Baseline (Cycle Day 1, 2 h)
70.2
(11.7)
70.2
(11.7)
70.8
(12.2)
71.8
(12.5)
71.8
(12.5)
Change at Cycle Day 1, 2 h
5.2
(4.3)
8.1
(6.7)
13.8
(7.2)
15.3
(7.2)
10.4
(5.8)
Time Matched Baseline (Cycle Day 1, 4 h)
68.5
(10.4)
68.5
(10.4)
68.3
(10.9)
68.4
(11.6)
68.4
(11.6)
Change at Cycle Day 1, 4 h
1.3
(6.2)
5.2
(7.7)
5.1
(7.5)
8.4
(6.8)
5.0
(4.5)
Time Matched Baseline (Cycle Day 1, 8 h)
68.8
(10.9)
68.8
(10.9)
68.6
(11.5)
68.9
(12.1)
68.9
(12.1)
Change at Cycle Day 1, 8 h
5.3
(6.3)
4.0
(3.8)
2.7
(4.8)
2.7
(5.8)
4.1
(4.9)
Time Matched Baseline (Cycle Day 1, 12 h)
69.7
(11.5)
69.7
(11.5)
70.0
(12.1)
70.2
(12.8)
70.2
(12.8)
Change at Cycle Day 1, 12 h
6.4
(6.3)
5.2
(5.9)
2.7
(4.0)
6.2
(7.3)
3.8
(5.2)
Time Matched Baseline (Cycle Day 3, 0 h)
67.9
(11.9)
67.9
(11.9)
66.6
(11.7)
67.1
(12.3)
67.1
(12.3)
Change at Cycle Day 3, 0 h
-2.1
(4.2)
-1.0
(6.4)
0.7
(6.1)
-0.7
(2.9)
-0.2
(3.8)
Time Matched Baseline (Cycle Day 3, 1 h)
70.2
(13.6)
70.2
(13.6)
70.6
(14.3)
71.2
(15.0)
71.2
(15.0)
Change at Cycle Day 3, 1 h
5.7
(8.6)
7.4
(9.9)
8.2
(5.4)
10.8
(6.9)
12.0
(6.4)
Time Matched Baseline (Cycle Day 3, 2 h)
73.8
(15.0)
73.8
(15.0)
74.2
(15.9)
75.6
(16.4)
75.6
(16.4)
Change at Cycle Day 3, 2 h
3.7
(6.2)
5.1
(6.2)
8.0
(6.3)
10.3
(6.9)
10.4
(8.3)
Time Matched Baseline (Cycle Day 3, 8 h)
71.0
(12.9)
71.0
(12.9)
69.8
(14.1)
70.8
(14.1)
70.8
(14.1)
Change at Cycle Day 3, 8 h
1.6
(5.9)
-0.6
(8.4)
-0.6
(5.2)
2.1
(6.5)
6.7
(14.4)
21. Primary Outcome
Title Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Description Study baseline is defined as the Day -1 assessment.
Time Frame 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

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description Placebo taken once daily Day 1-Day 3 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 11 10 9 9
Study Baseline
136.3
(12.9)
136.3
(12.9)
136.3
(12.9)
133.9
(10.8)
132.9
(10.9)
132.9
(10.9)
Change at Cycle Day 1, 0 h
-8.9
(9.9)
-9.8
(19.6)
-18.7
(16.4)
-16.1
(10.3)
-15.0
(14.3)
-16.1
(15.7)
Change at Cycle Day 1, 1 h
-14.8
(13.0)
-18.1
(18.7)
-25.6
(16.8)
-24.0
(13.5)
-22.9
(13.2)
-27.2
(13.5)
Change at Cycle Day 1, 2 h
-17.3
(11.5)
-22.5
(17.8)
-27.5
(15.7)
-27.9
(14.5)
-26.6
(16.8)
-27.2
(15.1)
Change at Cycle Day 1, 4 h
-13.5
(10.7)
-18.4
(13.0)
-24.4
(13.4)
-23.9
(15.1)
-27.0
(14.7)
-25.3
(16.7)
Change at Cycle Day 1, 8 h
-16.6
(12.0)
-17.7
(13.5)
-25.3
(11.5)
-21.7
(13.5)
-24.3
(14.4)
-30.6
(15.5)
Change at Cycle Day 1, 12 h
-14.4
(12.7)
-15.5
(16.8)
-23.8
(13.4)
-20.9
(14.2)
-22.3
(15.6)
-23.4
(17.4)
Change at Cycle Day 3, 0 h
-13.3
(15.0)
-13.0
(16.1)
-18.3
(16.1)
-18.5
(15.1)
-16.9
(11.5)
-18.8
(16.7)
Change at Cycle Day 3, 1 h
-16.1
(15.6)
-22.1
(17.8)
-24.9
(21.1)
-26.3
(15.1)
-24.7
(16.3)
-25.7
(13.5)
Change at Cycle Day 3, 2 h
-16.1
(15.5)
-23.2
(16.7)
-27.7
(18.7)
-28.8
(15.7)
-28.0
(12.8)
-26.6
(12.0)
Change at Cycle Day 3, 8 h
-15.4
(15.0)
-20.5
(14.6)
-23.5
(16.3)
-26.2
(12.5)
-24.9
(14.3)
-20.6
(13.5)
22. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
Description 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 Frame 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

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 10 9 9
Time Matched Baseline (Cycle Day 1, 0 h)
127.4
(9.1)
127.4
(9.1)
126.3
(8.9)
125.2
(8.7)
125.2
(8.7)
Change at Cycle Day 1, 0 h
-0.9
(14.0)
-9.8
(9.9)
-8.5
(7.9)
-7.3
(7.4)
-8.4
(11.8)
Time Matched Baseline (Cycle Day 1, 1 h)
121.5
(11.3)
121.5
(11.3)
121.2
(11.8)
119.7
(11.5)
119.7
(11.5)
Change at Cycle Day 1, 1 h
-3.3
(12.1)
-10.8
(11.1)
-11.3
(10.6)
-9.7
(11.4)
-14.0
(11.5)
Time Matched Baseline (Cycle Day 1, 2 h)
119.0
(8.8)
119.0
(8.8)
117.6
(7.9)
117.2
(8.3)
117.2
(8.3)
Change at Cycle Day 1, 2 h
-5.3
(11.4)
-10.3
(11.4)
-11.6
(7.5)
-10.9
(8.1)
-11.6
(6.8)
Time Matched Baseline (Cycle Day 1, 4 h)
122.7
(6.4)
122.7
(6.4)
121.8
(5.9)
120.7
(4.9)
120.7
(4.9)
Change at Cycle Day 1, 4 h
-4.8
(8.8)
-10.8
(11.3)
-11.8
(11.6)
-14.8
(10.4)
-13.1
(10.4)
Time Matched Baseline (Cycle Day 1, 8 h)
119.6
(9.9)
119.6
(9.9)
117.3
(6.5)
116.4
(6.3)
116.4
(6.3)
Change at Cycle Day 1, 8 h
-1.1
(12.8)
-8.6
(11.1)
-5.1
(11.4)
-7.9
(11.4)
-14.1
(9.3)
Time Matched Baseline (Cycle Day 1, 12 h)
121.9
(10.7)
121.9
(10.7)
120.7
(10.4)
119.0
(9.5)
119.0
(9.5)
Change at Cycle Day 1, 12 h
-1.2
(13.7)
-9.5
(9.8)
-7.7
(10.7)
-8.4
(9.2)
-9.6
(12.5)
Time Matched Baseline (Cycle Day 3, 0 h)
123.0
(11.4)
123.0
(11.4)
124.0
(11.5)
124.3
(12.1)
124.3
(12.1)
Change at Cycle Day 3, 0 h
0.3
(11.3)
-5.0
(12.2)
-8.6
(10.8)
-8.3
(10.2)
-10.2
(16.6)
Time Matched Baseline (Cycle Day 3, 1 h)
120.2
(12.6)
120.2
(12.6)
121.0
(12.9)
121.3
(13.7)
121.3
(13.7)
Change at Cycle Day 3, 1 h
-6.0
(7.9)
-8.8
(10.4)
-13.4
(11.3)
-13.1
(15.7)
-14.1
(10.6)
Time Matched Baseline (Cycle Day 3, 2 h)
119.2
(10.8)
119.2
(10.8)
119.4
(11.5)
120.4
(11.9)
120.4
(11.9)
Change at Cycle Day 3, 2 h
-5.5
(6.8)
-10.4
(6.0)
-13.9
(5.0)
-16.3
(9.5)
-14.8
(4.7)
Time Matched Baseline (Cycle Day 3, 8 h)
120.9
(12.0)
120.9
(12.0)
120.6
(13.2)
122.1
(13.1)
122.1
(13.1)
Change at Cycle Day 3, 8 h
-5.1
(10.3)
-8.1
(9.2)
-12.1
(10.6)
-14.1
(10.4)
-9.8
(13.9)
23. Primary Outcome
Title Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Description Study baseline is defined as the Day -1 assessment.
Time Frame 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

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description Placebo taken once daily Day 1-Day 3 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 11 10 9 9
Study Baseline
80.4
(5.9)
80.4
(5.9)
80.4
(5.9)
79.9
(6.0)
78.2
(2.9)
78.2
(2.9)
Change at Cycle Day 1, 0 h
-3.3
(5.1)
-4.4
(9.2)
-6.9
(6.9)
-6.4
(6.8)
-6.3
(5.6)
-5.9
(6.1)
Change at Cycle Day 1, 1 h
-6.8
(6.8)
-7.9
(8.4)
-12.5
(8.2)
-13.3
(7.0)
-11.3
(5.5)
-13.7
(6.0)
Change at Cycle Day 1, 2 h
-8.4
(7.4)
-10.9
(9.4)
-12.9
(7.5)
-16.3
(8.2)
-11.7
(6.6)
-13.3
(5.9)
Change at Cycle Day 1, 4 h
-8.2
(4.9)
-8.2
(7.3)
-10.1
(5.8)
-11.7
(6.6)
-12.0
(4.9)
-10.8
(5.5)
Change at Cycle Day 1, 8 h
-7.2
(7.5)
-6.7
(8.7)
-11.5
(6.3)
-10.1
(8.8)
-8.4
(7.7)
-13.3
(6.8)
Change at Cycle Day 1, 12 h
-6.5
(6.6)
-8.6
(8.7)
-9.7
(10.6)
-10.3
(9.7)
-9.9
(6.8)
-11.0
(9.4)
Change at Cycle Day 3, 0 h
-4.6
(6.7)
-2.6
(6.9)
-5.6
(7.1)
-7.0
(6.5)
-7.4
(5.4)
-5.3
(6.8)
Change at Cycle Day 3, 1 h
-7.6
(7.9)
-10.9
(9.1)
-14.1
(9.6)
-13.6
(8.8)
-13.3
(6.3)
-13.2
(6.3)
Change at Cycle Day 3, 2 h
-4.8
(8.6)
-10.5
(8.9)
-13.5
(8.4)
-12.3
(10.7)
-12.2
(5.6)
-16.3
(5.3)
Change at Cycle Day 3, 8 h
-7.5
(7.8)
-9.1
(8.5)
-11.2
(6.2)
-12.1
(8.3)
-10.9
(5.3)
-9.4
(5.6)
24. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
Description 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 Frame 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

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 10 9 9
Time Matched Baseline (Cycle Day 1, 0 h)
77.1
(5.3)
77.1
(5.3)
77.0
(5.6)
75.7
(3.8)
75.7
(3.8)
Change at Cycle Day 1, 0 h
-1.1
(6.2)
-3.6
(3.7)
-3.5
(4.4)
-3.8
(2.5)
-3.3
(4.9)
Time Matched Baseline (Cycle Day 1, 1 h)
73.5
(8.0)
73.5
(8.0)
74.1
(8.2)
72.1
(5.6)
72.1
(5.6)
Change at Cycle Day 1, 1 h
-1.1
(6.5)
-5.6
(7.4)
-7.5
(7.3)
-5.2
(5.3)
-7.6
(5.8)
Time Matched Baseline (Cycle Day 1, 2 h)
72.0
(5.5)
72.0
(5.5)
71.9
(5.8)
71.4
(5.9)
71.4
(5.9)
Change at Cycle Day 1, 2 h
-2.5
(6.0)
-4.5
(5.4)
-8.3
(4.7)
-4.9
(6.8)
-6.6
(5.7)
Time Matched Baseline (Cycle Day 1, 4 h)
72.2
(6.1)
72.2
(6.1)
72.5
(6.4)
71.0
(4.5)
71.0
(4.5)
Change at Cycle Day 1, 4 h
0
(7.0)
-1.9
(6.1)
-4.3
(6.6)
-4.8
(6.0)
-3.6
(3.3)
Time Matched Baseline (Cycle Day 1, 8 h)
73.2
(7.3)
73.2
(7.3)
71.9
(6.2)
70.9
(5.7)
70.9
(5.7)
Change at Cycle Day 1, 8 h
0.5
(9.9)
-4.3
(8.4)
-2.1
(7.9)
-1.1
(10.6)
-6.0
(6.2)
Time Matched Baseline (Cycle Day 1, 12 h)
73.8
(7.7)
73.8
(7.7)
72.9
(7.4)
71.3
(5.9)
71.3
(5.9)
Change at Cycle Day 1, 12 h
-2.1
(7.2)
-3.2
(10.7)
-3.3
(6.8)
-3.0
(5.4)
-4.1
(5.6)
Time Matched Baseline (Cycle Day 3, 0 h)
75.7
(4.3)
75.7
(4.3)
76.1
(4.4)
75.7
(4.4)
75.7
(4.4)
Change at Cycle Day 3, 0 h
2.0
(4.4)
-1.0
(4.8)
-3.2
(4.6)
-4.9
(3.3)
-2.8
(6.3)
Time Matched Baseline (Cycle Day 3, 1 h)
72.7
(6.1)
72.7
(6.1)
72.9
(6.3)
72.6
(6.6)
72.6
(6.6)
Change at Cycle Day 3, 1 h
-3.3
(4.6)
-6.5
(6.0)
-6.6
(5.9)
-7.7
(7.3)
-7.6
(5.5)
Time Matched Baseline (Cycle Day 3, 2 h)
75.6
(6.3)
75.6
(6.3)
75.3
(6.7)
75.4
(7.1)
75.4
(7.1)
Change at Cycle Day 3, 2 h
-5.1
(4.0)
-8.0
(6.4)
-7.0
(6.2)
-8.5
(4.9)
-13.3
(5.1)
Time Matched Baseline (Cycle Day 3, 8 h)
72.8
(6.5)
72.8
(6.5)
73.0
(6.8)
73.0
(6.8)
73.0
(6.8)
Change at Cycle Day 3, 8 h
-1.5
(5.5)
-3.6
(4.0)
-4.8
(5.3)
-5.7
(3.9)
-4.2
(5.5)
25. Primary Outcome
Title Orthostatic Pulse Over Time
Description An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Time Frame 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

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description Placebo taken once daily Day 1-Day 3 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 11 10 9 9
Cycle Day 1, Predose
9.7
(3.8)
11.6
(5.6)
11.0
(4.1)
11.9
(3.8)
11.0
(3.9)
10.4
(2.7)
Cycle Day 1, 1 h
9.7
(5.4)
11.5
(7.1)
12.6
(6.4)
17.8
(6.1)
17.8
(7.6)
16.0
(7.4)
Cycle Day 1, 2 h
10.9
(4.1)
10.6
(5.9)
12.3
(8.4)
14.6
(6.8)
13.9
(5.9)
15.6
(5.7)
Cycle Day 1, 4 h
9.5
(7.7)
10.3
(9.5)
11.0
(6.4)
14.6
(5.3)
12.3
(9.3)
14.8
(8.0)
Cycle Day 1, 8 h
10.8
(7.8)
10.3
(6.7)
12.7
(6.5)
13.0
(3.4)
15.2
(4.4)
11.0
(7.6)
Cycle Day 1, 12 h
10.7
(4.8)
10.6
(5.1)
9.9
(13.0)
10.8
(7.5)
13.0
(7.4)
11.3
(6.8)
26. Primary Outcome
Title Orthostatic Systolic Blood Pressure Over Time
Description An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Time Frame 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

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description Placebo taken once daily Day 1-Day 3 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 11 10 9 9
Cycle Day 1, Predose
4.4
(7.2)
3.7
(6.5)
5.9
(7.3)
4.0
(13.0)
3.4
(5.3)
4.2
(9.1)
Cycle Day 1, 1 h
7.0
(5.6)
9.1
(8.4)
5.2
(3.5)
5.8
(8.2)
4.0
(6.8)
6.2
(6.7)
Cycle Day 1, 2 h
8.5
(12.4)
8.2
(4.6)
6.2
(8.7)
7.3
(8.4)
3.3
(6.5)
4.6
(8.3)
Cycle Day 1, 4 h
3.6
(9.2)
3.2
(8.7)
4.2
(5.8)
4.3
(5.0)
6.3
(9.2)
6.7
(7.7)
Cycle Day 1, 8 h
8.4
(5.8)
5.4
(5.8)
8.1
(14.1)
5.5
(7.8)
5.6
(4.9)
8.0
(4.5)
Cycle Day 1, 12 h
9.7
(10.5)
6.2
(5.3)
6.0
(6.1)
8.0
(6.7)
2.1
(4.5)
3.4
(7.9)
27. Primary Outcome
Title Orthostatic Diastolic Blood Pressure Over Time
Description An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Time Frame 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

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description Placebo taken once daily Day 1-Day 3 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 11 10 9 9
Cycle Day 1, Predose
7.0
(2.4)
9.3
(4.7)
8.1
(7.7)
5.7
(5.1)
8.3
(2.7)
7.4
(4.4)
Cycle Day 1, 1 h
6.9
(4.1)
7.0
(3.9)
6.5
(3.7)
4.7
(4.4)
5.7
(3.6)
5.8
(3.8)
Cycle Day 1, 2 h
10.5
(6.5)
8.3
(3.5)
6.5
(5.6)
7.6
(3.7)
3.2
(7.2)
4.2
(4.6)
Cycle Day 1, 4 h
9.1
(3.6)
6.6
(7.8)
4.9
(4.3)
5.1
(3.1)
6.2
(2.7)
6.9
(5.5)
Cycle Day 1, 8 h
9.1
(7.1)
6.0
(5.5)
7.9
(5.2)
5.5
(3.4)
4.7
(7.6)
7.0
(5.0)
Cycle Day 1, 12 h
8.6
(7.7)
7.9
(3.9)
5.5
(6.2)
9.3
(6.3)
6.6
(2.5)
6.2
(4.3)
28. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure
Description 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 Frame Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 10 10 10 9 9
0-4 hrs: Time Matched Baseline
125.67
(10.39)
125.67
(10.39)
125.67
(10.39)
125.72
(11.02)
125.72
(11.02)
0-4 hrs: Cycle Day 2 Change
-5.18
(5.70)
-10.57
(8.67)
-8.98
(9.08)
-11.57
(11.00)
-13.15
(12.59)
4-8 hrs: Time Matched Baseline
124.28
(8.07)
124.28
(8.07)
124.28
(8.07)
123.32
(7.94)
123.32
(7.94)
4-8 hrs: Cycle Day 2 Change
-5.56
(10.61)
-9.45
(9.68)
-9.03
(12.55)
-13.26
(11.78)
-14.18
(10.07)
8-12 hrs: Time Matched Baseline
128.95
(9.99)
128.95
(9.99)
128.95
(9.99)
127.42
(9.26)
127.42
(9.26)
8-12 hrs: Cycle Day 2 Change
-2.65
(12.85)
-8.80
(14.91)
-6.81
(10.27)
-10.51
(12.34)
-11.93
(13.47)
29. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
Description 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 Frame 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

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 10 10 10 9 9
0.5 hr: Time Matched Baseline
140.30
(18.66)
140.30
(18.66)
140.30
(18.66)
138.22
(18.53)
138.22
(18.53)
0.5 hr: Cycle Day 2 Change
-4.90
(6.89)
-14.80
(8.78)
-10.10
(10.09)
-11.67
(13.06)
-10.67
(9.95)
1 hr: Time Matched Baseline
128.60
(12.56)
128.60
(12.56)
128.60
(12.56)
128.89
(13.29)
128.89
(13.29)
1 hr: Cycle Day 2 Change
-7.70
(12.36)
-12.50
(14.00)
-10.80
(16.19)
-8.56
(17.41)
-14.22
(15.74)
1.5 hrs: Time Matched Baseline
125.10
(13.99)
125.10
(13.99)
125.10
(13.99)
125.67
(14.71)
125.67
(14.71)
1.5 hrs: Cycle Day 2 Change
-5.00
(11.75)
-9.10
(18.46)
-10.40
(14.39)
-14.33
(12.71)
-13.67
(16.81)
2 hrs: Time Matched Baseline
122.70
(10.68)
122.70
(10.68)
122.70
(10.68)
123.22
(11.19)
123.22
(11.19)
2 hrs: Cycle Day 2 Change
-5.10
(14.42)
-6.30
(10.56)
-8.90
(9.92)
-12.56
(13.25)
-13.11
(16.32)
2.5 hrs: Time Matched Baseline
120.20
(6.05)
120.20
(6.05)
120.20
(6.05)
120.22
(6.42)
120.22
(6.42)
2.5 hrs: Cycle Day 2 Change
0
(13.55)
-10.10
(12.56)
-7.40
(12.81)
-13.11
(13.16)
-12.33
(12.11)
3 hrs: Time Matched Baseline
119.10
(13.04)
119.10
(13.04)
119.10
(13.04)
118.78
(13.79)
118.78
(13.79)
3 hrs: Cycle Day 2 Change
-3.20
(16.29)
-6.40
(19.78)
-4.70
(17.61)
-8.22
(18.77)
-11.56
(18.42)
3.5 hrs: Time Matched Baseline
120.89
(13.77)
120.89
(13.77)
120.89
(13.77)
120.75
(14.71)
120.75
(14.71)
3.5 hrs: Cycle Day 2 Change
-6.56
(15.95)
-14.11
(14.29)
-10.67
(12.36)
-9.25
(19.03)
-12.88
(22.40)
4 hrs: Time Matched Baseline
126.30
(12.57)
126.30
(12.57)
123.78
(10.31)
127.56
(12.65)
127.56
(12.65)
4 hrs: Cycle Day 2 Change
-8.00
(8.94)
-11.30
(12.70)
-5.56
(13.31)
-13.78
(12.66)
-15.33
(18.41)
4.5 hrs: Time Matched Baseline
129.80
(13.60)
129.80
(13.60)
129.80
(13.60)
127.33
(11.82)
127.33
(11.82)
4.5 hrs: Cycle Day 2 Change
-10.70
(11.98)
-10.50
(14.69)
-14.70
(10.71)
-8.78
(11.20)
-13.44
(17.40)
5 hrs: Time Matched Baseline
120.80
(14.44)
120.80
(14.44)
120.80
(14.44)
119.56
(14.73)
119.56
(14.73)
5 hrs: Cycle Day 2 Change
-1.90
(13.89)
-6.20
(14.54)
-5.20
(19.86)
-7.33
(17.33)
-11.67
(17.43)
5.5 hrs: Time Matched Baseline
123.50
(16.18)
123.50
(16.18)
123.50
(16.18)
123.33
(17.15)
123.33
(17.15)
5.5 hrs: Cycle Day 2 Change
-3.10
(15.74)
-9.40
(14.95)
-9.20
(14.90)
-18.11
(19.66)
-17.44
(20.73)
6 hrs: Time Matched Baseline
122.00
(11.27)
124.89
(7.01)
122.00
(11.27)
120.78
(11.23)
120.78
(11.23)
6 hrs: Cycle Day 2 Change
-6.90
(16.04)
-12.00
(11.86)
-7.80
(13.80)
-15.33
(17.73)
-16.11
(14.48)
6.5 hrs: Time Matched Baseline
121.40
(7.68)
121.40
(7.68)
121.40
(7.68)
121.44
(8.14)
121.44
(8.14)
6.5 hrs: Cycle Day 2 Change
-2.00
(17.95)
-7.60
(15.90)
-4.60
(17.60)
-12.44
(18.41)
-14.44
(13.97)
7 hrs: Time Matched Baseline
125.50
(10.17)
125.50
(10.17)
125.50
(10.17)
126.22
(10.51)
126.22
(10.51)
7 hrs: Cycle Day 2 Change
-5.50
(13.88)
-11.60
(15.28)
-10.70
(16.34)
-15.44
(13.46)
-13.78
(11.36)
7.5 hrs: Time Matched Baseline
126.30
(12.31)
126.30
(12.31)
126.30
(12.31)
125.44
(12.74)
125.44
(12.74)
7.5 hrs: Cycle Day 2 Change
-8.00
(16.80)
-12.30
(17.75)
-12.30
(21.43)
-16.56
(22.57)
-14.33
(20.27)
8 hrs: Time Matched Baseline
124.90
(12.68)
124.90
(12.68)
124.90
(12.68)
122.44
(10.63)
122.44
(10.63)
8 hrs: Cycle Day 2 Change
-6.40
(21.29)
-9.10
(13.54)
-7.70
(19.81)
-12.11
(22.83)
-12.22
(15.70)
8.5 hrs: Time Matched Baseline
126.10
(12.13)
126.10
(12.13)
125.11
(12.43)
123.89
(10.52)
123.89
(10.52)
8.5 hrs: Cycle Day 2 Change
-5.00
(13.32)
-8.40
(17.58)
-1.33
(9.42)
-12.11
(16.97)
-12.11
(17.51)
9 hrs: Time Matched Baseline
127.20
(11.12)
127.20
(11.12)
127.20
(11.12)
125.67
(10.62)
125.67
(10.62)
9 hrs: Cycle Day 2 Change
-2.60
(17.44)
-7.90
(21.66)
-7.20
(18.33)
-13.78
(19.77)
-15.44
(15.16)
9.5 hrs: Time Matched Baseline
128.30
(14.38)
128.30
(14.38)
128.30
(14.38)
126.78
(14.38)
126.78
(14.38)
9.5 hrs: Cycle Day 2 Change
-1.90
(23.19)
-14.00
(22.14)
-4.70
(18.69)
-12.11
(22.79)
-11.56
(19.64)
10 hrs: Time Matched Baseline
128.56
(14.78)
128.56
(14.78)
128.56
(14.78)
126.50
(14.36)
126.50
(14.36)
10 hrs: Cycle Day 2 Change
-2.78
(20.11)
-10.67
(19.54)
-5.44
(13.42)
-9.63
(22.49)
-4.25
(24.81)
10.5 hrs: Time Matched Baseline
136.90
(19.17)
137.89
(20.07)
136.90
(19.17)
133.33
(16.45)
133.33
(16.45)
10.5 hrs: Cycle Day 2 Change
-5.20
(22.09)
-5.78
(18.03)
-8.10
(16.13)
-11.33
(11.96)
-11.78
(16.28)
11 hrs: Time Matched Baseline
133.44
(14.97)
133.70
(14.13)
133.44
(14.97)
133.11
(14.86)
133.11
(14.86)
11 hrs: Cycle Day 2 Change
-3.00
(16.05)
-15.50
(11.64)
-12.56
(9.17)
-15.78
(16.54)
-19.00
(21.04)
11.5 hrs: Time Matched Baseline
126.30
(10.04)
126.30
(10.04)
126.30
(10.04)
126.11
(10.64)
126.11
(10.64)
11.5 hrs: Cycle Day 2 Change
-3.20
(8.40)
-3.20
(12.93)
-8.70
(6.06)
-4.56
(8.26)
-12.22
(14.01)
12 hrs: Time Matched Baseline
124.05
(9.42)
124.05
(9.42)
124.05
(9.42)
123.17
(9.55)
123.17
(9.55)
12 hrs: Cycle Day 2 Change
3.45
(9.54)
-4.10
(13.33)
-2.55
(10.93)
-4.94
(7.27)
-6.72
(14.85)
30. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
Description 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 Frame Time-Matched Baseline (Placebo Cycle); Cycle Day 2

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 10 10 10 9 9
Time-Matched Baseline
126.27
(8.62)
126.27
(8.62)
126.27
(8.62)
125.45
(8.72)
125.45
(8.72)
Cycle Day 2 Change
-4.42
(8.59)
-9.55
(9.98)
-8.22
(9.74)
-11.74
(10.71)
-13.05
(10.66)
31. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure
Description 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 Frame Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 10 10 10 9 9
0-4 hrs: Time Matched Baseline
75.59
(6.05)
75.59
(6.05)
75.59
(6.05)
74.94
(6.04)
74.94
(6.04)
0-4 hrs: Cycle Day 2 Change
-2.96
(3.75)
-7.59
(6.04)
-5.96
(5.53)
-7.94
(4.75)
-8.32
(6.28)
4-8 hrs: Time Matched Baseline
74.54
(7.54)
74.54
(7.54)
74.54
(7.54)
72.88
(5.74)
72.88
(5.74)
4-8 hrs: Cycle Day 2 Change
-2.28
(7.46)
-4.03
(6.37)
-3.49
(8.91)
-7.61
(5.88)
-5.92
(7.12)
8-12 hrs: Time Matched Baseline
77.05
(6.31)
77.05
(6.31)
77.05
(6.31)
75.75
(5.08)
75.75
(5.08)
8-12 hrs: Cycle Day 2 Change
1.41
(5.71)
-3.70
(5.89)
-1.45
(4.79)
-4.63
(4.92)
-4.84
(6.78)
32. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
Description 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 Frame 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

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 10 10 10 9 9
0.5 hr: Time Matched Baseline
87.90
(7.45)
87.90
(7.45)
87.90
(7.45)
86.44
(6.21)
86.44
(6.21)
0.5 hr: Cycle Day 2 Change
-2.40
(6.04)
-8.70
(11.37)
-2.60
(6.50)
-7.56
(6.48)
-7.44
(9.81)
1 hr: Time Matched Baseline
77.90
(8.58)
77.90
(8.58)
77.90
(8.58)
77.11
(8.71)
77.11
(8.71)
1 hr: Cycle Day 2 Change
-2.70
(7.29)
-10.40
(5.38)
-6.30
(10.63)
-7.56
(6.11)
-11.33
(8.08)
1.5 hrs: Time Matched Baselline
73.70
(11.02)
73.70
(11.02)
73.70
(11.02)
72.89
(11.36)
72.89
(11.36)
1.5 hrs: Cycle Day 2 Change
-4.70
(11.54)
-6.30
(17.63)
-9.20
(10.61)
-9.78
(12.36)
-10.11
(10.76)
2 hrs: Time Matched Baseline
72.30
(7.59)
72.30
(7.59)
72.30
(7.59)
71.00
(6.76)
71.00
(6.76)
2 hrs: Cycle Day 2 Change
-3.10
(8.54)
-5.60
(10.41)
-7.40
(8.37)
-5.33
(10.99)
-7.89
(9.40)
2.5 hrs: Time Matched Baseline
72.20
(7.93)
72.20
(7.93)
72.20
(7.93)
71.89
(8.34)
71.89
(8.34)
2.5 hrs: Cycle Day 2 Change
-3.10
(12.91)
-9.70
(14.30)
-5.80
(11.59)
-11.11
(8.91)
-6.22
(9.90)
3 hrs: Time Matched Baseline
73.50
(11.83)
73.50
(11.83)
73.50
(11.83)
73.44
(12.55)
73.44
(12.55)
3 hrs: Cycle Day 2 Change
-5.00
(9.82)
-7.90
(15.67)
-8.50
(14.18)
-8.44
(9.62)
-7.78
(17.50)
3.5 hrs: Time Matched Baseline
70.33
(9.70)
70.33
(9.70)
70.33
(9.70)
69.50
(10.01)
69.50
(10.01)
3.5 hrs: Cycle Day 2 Change
-1.67
(12.57)
-6.89
(11.04)
-3.78
(9.19)
-8.00
(11.83)
-5.88
(13.89)
4 hrs: Time Matched Baseline
76.60
(6.02)
76.60
(6.02)
76.33
(6.32)
76.89
(6.31)
76.89
(6.31)
4 hrs: Cycle Day 2 Change
-1.90
(6.40)
-6.10
(6.08)
-2.22
(11.02)
-6.56
(9.58)
-9.67
(9.71)
4.5 hrs: Time Matched Baseline
79.40
(12.88)
79.40
(12.88)
79.40
(12.88)
76.56
(9.77)
76.56
(9.77)
4.5 hrs: Cycle Day 2 Change
-1.60
(11.72)
-5.80
(11.11)
-7.30
(9.78)
-3.78
(7.29)
-6.44
(7.84)
5 hrs: Time Matched Baseline
70.10
(14.10)
70.10
(14.10)
70.10
(14.10)
67.78
(12.76)
67.78
(12.76)
5 hrs: Cycle Day 2 Change
-1.20
(14.65)
1.70
(14.24)
-0.70
(13.49)
0.11
(14.17)
-0.67
(14.49)
5.5 hrs: Time Matched Baseline
75.30
(7.54)
75.30
(7.54)
75.30
(7.54)
74.22
(7.14)
74.22
(7.14)
5.5 hrs: Cycle Day 2 Change
-3.30
(9.19)
-6.00
(8.88)
-5.00
(7.62)
-14.67
(10.85)
-9.33
(9.63)
6 hrs: Time Matched Baseline
74.80
(7.67)
75.89
(7.27)
74.80
(7.67)
73.44
(6.75)
73.44
(6.75)
6 hrs: Cycle Day 2 Change
-5.70
(16.38)
-7.44
(9.86)
-6.10
(10.87)
-15.22
(10.72)
-8.11
(10.45)
6.5 hrs: Time Matched Baseline
73.60
(7.17)
73.60
(7.17)
73.60
(7.17)
72.67
(6.93)
72.67
(6.93)
6.5 hrs: Cycle Day 2 Change
-3.70
(12.28)
-5.30
(6.86)
-3.20
(14.86)
-8.00
(10.81)
-8.78
(12.34)
7 hrs: Time Matched Baseline
75.70
(7.76)
75.70
(7.76)
75.70
(7.76)
74.67
(7.47)
74.67
(7.47)
7 hrs: Cycle Day 2 Change
-1.50
(10.56)
-5.60
(10.39)
-1.70
(12.46)
-11.22
(10.11)
-4.78
(11.98)
7.5 hrs: Time Matched Baseline
73.70
(12.29)
73.70
(12.29)
73.70
(12.29)
71.89
(11.54)
71.89
(11.54)
7.5 hrs: Cycle Day 2 Change
-0.80
(12.65)
-3.50
(14.73)
-3.20
(16.51)
-2.78
(15.71)
-4.11
(20.57)
8 hrs: Time Matched Baseline
73.70
(13.28)
73.70
(13.28)
73.70
(13.28)
71.78
(12.52)
71.78
(12.52)
8 hrs: Cycle Day 2 Change
-0.40
(15.46)
-1.80
(12.93)
-0.70
(13.56)
-5.33
(17.05)
-5.11
(18.45)
8.5 hrs: Time Matched Baseline
73.70
(9.26)
73.70
(9.26)
73.33
(9.75)
71.33
(5.79)
71.33
(5.79)
8.5 hrs: Cycle Day 2 Change
2.20
(9.85)
-3.60
(7.60)
0.89
(10.48)
-2.67
(10.23)
-2.78
(11.22)
9 hrs: Time Matched Baseline
75.90
(10.34)
75.90
(10.34)
75.90
(10.34)
74.22
(9.42)
74.22
(9.42)
9 hrs: Cycle Day 2 Change
3.80
(11.51)
-0.90
(13.92)
-0.80
(12.86)
-6.67
(12.74)
-6.67
(12.13)
9.5 hrs: Time Matched Baseline
80.90
(10.28)
80.90
(10.28)
80.90
(10.28)
80.00
(10.48)
80.00
(10.48)
9.5 hrs: Cycle Day 2 Change
0.60
(13.48)
-12.20
(11.63)
-3.60
(15.04)
-9.78
(11.38)
-7.11
(13.36)
10 hrs: Time Matched Baseline
79.56
(7.32)
79.56
(7.32)
79.56
(7.32)
78.63
(7.23)
78.63
(7.23)
10 hrs: Cycle Day 2 Change
0.56
(10.45)
-3.67
(9.68)
-1.78
(4.66)
-7.75
(13.04)
-3.75
(12.69)
10.5 hrs: Time Matched Baseline
83.60
(10.24)
84.22
(10.66)
83.60
(10.24)
82.56
(10.28)
82.56
(10.28)
10.5 hrs: Cycle Day 2 Change
-2.80
(9.38)
-4.56
(9.15)
-1.60
(4.88)
-8.11
(11.24)
-9.22
(10.10)
11 hrs: Time Matched Baseline
76.22
(8.45)
77.00
(8.34)
76.22
(8.45)
75.89
(8.02)
75.89
(8.02)
11 hrs: Cycle Day 2 Change
0.89
(10.56)
-5.40
(7.85)
-5.56
(8.00)
-6.44
(9.94)
-8.22
(12.08)
11.5 hrs: Time Matched Baseline
73.50
(9.96)
73.50
(9.96)
73.50
(9.96)
72.78
(10.28)
72.78
(10.28)
11.5 hrs: Cycle Day 2 Change
0.20
(9.50)
-0.50
(11.65)
-2.80
(8.07)
0.78
(10.37)
-2.78
(10.29)
12 hrs: Time Matched Baseline
73.20
(6.44)
73.20
(6.44)
73.20
(6.44)
71.56
(4.03)
71.56
(4.03)
12 hrs: Cycle Day 2 Change
5.30
(8.21)
-0.10
(5.57)
2.50
(12.06)
1.89
(9.49)
0.89
(8.37)
33. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Diastolic Blood Pressure
Description 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 Frame Time-Matched Baseline (Placebo Cycle); Cycle Day 2

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 10 10 10 9 9
Time-Matched Baseline
75.71
(6.27)
75.71
(6.27)
75.71
(6.27)
74.51
(5.28)
74.51
(5.28)
Cycle Day 2 Change
-1.26
(4.08)
-5.10
(4.67)
-3.59
(5.72)
-6.71
(4.38)
-6.34
(5.84)
34. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure
Description 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 Frame Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 10 10 10 9 9
0-4 hrs: Time Matched Baseline
92.61
(6.23)
92.61
(6.23)
92.61
(6.23)
92.21
(6.47)
92.21
(6.47)
0-4 hrs: Cycle Day 2 Change
-3.93
(3.38)
-8.93
(6.29)
-7.64
(6.16)
-9.13
(6.21)
-9.67
(8.37)
4-8 hrs: Time Matched Baseline
91.38
(6.49)
91.38
(6.49)
91.38
(6.49)
89.99
(5.06)
89.99
(5.06)
4-8 hrs: Cycle Day 2 Change
-3.50
(7.59)
-5.80
(6.58)
-5.55
(9.34)
-10.29
(6.73)
-8.65
(6.93)
8-12 hrs: Time Matched Baseline
93.99
(6.38)
93.99
(6.38)
93.99
(6.38)
92.51
(4.63)
92.51
(4.63)
8-12 hrs: Cycle Day 2 Change
0.36
(8.87)
-4.34
(7.72)
-3.00
(6.44)
-6.81
(5.80)
-6.58
(8.05)
35. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
Description 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 Frame 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

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 10 10 10 9 9
0.5 hr: Time Matched Baseline
104.50
(9.96)
104.50
(9.96)
104.50
(9.96)
102.00
(6.42)
102.00
(6.42)
0.5 hr: Cycle Day 2 Change
-3.70
(7.21)
-9.20
(10.99)
-3.90
(8.50)
-5.33
(6.06)
-4.11
(10.41)
1 hr: Time Matched Baseline
96.80
(7.73)
96.80
(7.73)
96.80
(7.73)
96.33
(8.05)
96.33
(8.05)
1 hr: Cycle Day 2 Change
-7.00
(7.73)
-12.70
(6.80)
-10.60
(11.05)
-10.11
(9.24)
-14.89
(9.31)
1.5 hrs: Time Matched Baseline
91.30
(13.02)
91.30
(13.02)
91.30
(13.02)
91.22
(13.81)
91.22
(13.81)
1.5 hrs: Cycle Day 2 Change
-5.20
(11.39)
-8.80
(17.82)
-10.00
(11.55)
-11.67
(14.97)
-12.00
(15.28)
2 hrs: Time Matched Baseline
89.20
(6.58)
89.20
(6.58)
89.20
(6.58)
88.44
(6.50)
88.44
(6.50)
2 hrs: Cycle Day 2 Change
-1.70
(11.16)
-6.10
(8.92)
-9.10
(8.52)
-8.11
(10.17)
-8.67
(16.51)
2.5 hrs: Time Matched Baseline
88.80
(6.70)
88.80
(6.70)
88.80
(6.70)
88.67
(7.09)
88.67
(7.09)
2.5 hrs: Cycle Day 2 Change
-2.40
(12.75)
-11.40
(15.25)
-7.20
(10.94)
-12.22
(9.86)
-10.11
(9.83)
3 hrs: Time Matched Baseline
88.10
(11.24)
88.10
(11.24)
88.10
(11.24)
88.22
(11.91)
88.22
(11.91)
3 hrs: Cycle Day 2 Change
-4.20
(10.54)
-6.90
(14.26)
-5.50
(15.17)
-8.78
(9.43)
-7.44
(17.26)
3.5 hrs: Time Matched Baseline
87.44
(10.08)
87.44
(10.08)
87.44
(10.08)
87.25
(10.75)
87.25
(10.75)
3.5 hrs: Cycle Day 2 Change
-3.89
(13.40)
-9.00
(11.24)
-6.56
(8.80)
-8.63
(13.16)
-7.50
(15.68)
4 hrs: Time Matched Baseline
94.10
(7.34)
94.10
(7.34)
92.78
(6.40)
94.78
(7.45)
94.78
(7.45)
4 hrs: Cycle Day 2 Change
-4.00
(8.46)
-7.90
(7.29)
-5.78
(10.33)
-8.78
(9.02)
-12.11
(13.60)
4.5 hrs: Time Matched Baseline
97.30
(10.92)
97.30
(10.92)
97.30
(10.92)
94.67
(7.50)
94.67
(7.50)
4.5 hrs: Cycle Day 2 Change
-4.30
(7.75)
-7.40
(10.16)
-11.30
(8.14)
-5.89
(2.93)
-9.67
(7.94)
5 hrs: Time Matched Baseline
86.60
(12.47)
86.60
(12.47)
86.60
(12.47)
84.56
(11.30)
84.56
(11.30)
5 hrs: Cycle Day 2 Change
-1.30
(14.03)
-0.80
(11.52)
-2.80
(15.51)
-3.00
(12.61)
-5.11
(12.29)
5.5 hrs: Time Matched Baseline
92.00
(7.21)
92.00
(7.21)
92.00
(7.21)
91.11
(7.04)
91.11
(7.04)
5.5 hrs: Cycle Day 2 Change
-3.40
(10.95)
-8.70
(8.38)
-7.10
(8.12)
-18.44
(10.03)
-13.33
(11.09)
6 hrs: Time Matched Baseline
90.70
(7.18)
92.33
(5.29)
90.70
(7.18)
89.78
(6.96)
89.78
(6.96)
6 hrs: Cycle Day 2 Change
-5.80
(14.99)
-9.00
(9.54)
-7.20
(11.06)
-15.56
(10.50)
-10.67
(11.15)
6.5 hrs: Time Matched Baseline
89.80
(6.41)
89.80
(6.41)
89.80
(6.41)
89.44
(6.69)
89.44
(6.69)
6.5 hrs: Cycle Day 2 Change
-3.50
(12.09)
-6.10
(9.18)
-4.40
(12.82)
-11.44
(11.07)
-11.33
(10.63)
7 hrs: Time Matched Baseline
92.90
(7.92)
92.90
(7.92)
92.90
(7.92)
92.44
(8.26)
92.44
(8.26)
7 hrs: Cycle Day 2 Change
-3.90
(12.06)
-8.50
(12.43)
-5.60
(12.73)
-14.11
(10.81)
-6.44
(11.67)
7.5 hrs: Time Matched Baseline
90.50
(11.72)
90.50
(11.72)
90.50
(11.72)
88.78
(11.01)
88.78
(11.01)
7.5 hrs: Cycle Day 2 Change
-2.70
(15.60)
-3.90
(15.15)
-3.70
(17.84)
-6.33
(16.67)
-5.44
(18.26)
8 hrs: Time Matched Baseline
91.20
(13.00)
91.20
(13.00)
91.20
(13.00)
89.11
(11.88)
89.11
(11.88)
8 hrs: Cycle Day 2 Change
-3.10
(17.12)
-3.90
(12.57)
-2.30
(15.82)
-7.56
(17.98)
-7.22
(13.63)
8.5 hrs: Time Matched Baseline
91.80
(10.08)
91.80
(10.08)
91.00
(10.34)
89.44
(7.20)
89.44
(7.20)
8.5 hrs: Cycle Day 2 Change
-0.80
(11.21)
-6.30
(9.26)
-0.89
(10.29)
-6.11
(12.73)
-6.33
(11.28)
9 hrs: Time Matched Baseline
92.00
(8.50)
92.00
(8.50)
92.00
(8.50)
90.44
(7.35)
90.44
(7.35)
9 hrs: Cycle Day 2 Change
3.30
(12.00)
-1.80
(14.61)
-1.30
(14.25)
-7.44
(12.41)
-8.11
(11.26)
9.5 hrs: Time Matched Baseline
96.40
(11.75)
96.40
(11.75)
96.40
(11.75)
95.22
(11.82)
95.22
(11.82)
9.5 hrs: Cycle Day 2 Change
1.50
(20.74)
-11.90
(14.81)
-3.40
(16.81)
-11.11
(15.32)
-8.22
(16.05)
10 hrs: Time Matched Baseline
95.11
(9.68)
95.11
(9.68)
95.11
(9.68)
93.63
(9.18)
93.63
(9.18)
10 hrs: Cycle Day 2 Change
-0.44
(14.79)
-4.89
(10.73)
-2.56
(7.99)
-9.75
(14.32)
-2.50
(18.24)
10.5 hrs: Time Matched Baseline
101.00
(10.84)
101.78
(11.20)
101.00
(10.84)
98.89
(9.06)
98.89
(9.06)
10.5 hrs: Cycle Day 2 Change
-2.70
(13.15)
-3.67
(10.95)
-3.50
(6.52)
-10.11
(7.69)
-10.67
(11.45)
11 hrs: Time Matched Baseline
95.00
(10.28)
95.50
(9.82)
95.00
(10.28)
94.33
(9.66)
94.33
(9.66)
11 hrs: Cycle Day 2 Change
-0.56
(11.17)
-7.10
(11.26)
-8.22
(9.92)
-10.00
(14.24)
-11.78
(14.70)
11.5 hrs: Time Matched Baseline
90.10
(8.45)
90.10
(8.45)
90.10
(8.45)
89.56
(8.78)
89.56
(8.78)
11.5 hrs: Cycle Day 2 Change
-1.40
(7.66)
0.60
(10.62)
-5.20
(5.39)
-0.78
(8.35)
-3.89
(7.46)
12 hrs: Time Matched Baseline
90.45
(6.30)
90.45
(6.30)
90.45
(6.30)
88.94
(4.37)
88.94
(4.37)
12 hrs: Cycle Day 2 Change
3.80
(7.63)
-0.25
(7.67)
0.95
(10.96)
-0.72
(6.64)
-0.89
(7.88)
36. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Mean Arterial Pressure
Description 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 Frame Time-Matched Baseline (Placebo Cycle); Cycle Day 2

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 10 10 10 9 9
Time-Matched Baseline
92.64
(5.77)
92.64
(5.77)
92.64
(5.77)
91.55
(4.90)
91.55
(4.90)
Cycle Day 2 Change
-2.33
(5.21)
-6.33
(5.44)
-5.34
(6.58)
-8.72
(5.43)
-8.28
(6.54)
37. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse
Description 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 Frame Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 10 10 10 9 9
0-4 hrs: Time Matched Baseline
75.61
(12.37)
75.61
(12.37)
75.61
(12.37)
76.59
(12.70)
76.59
(12.70)
0-4 hrs: Cycle Day 2 Change
2.49
(3.62)
6.11
(4.49)
8.91
(7.60)
7.10
(4.43)
7.38
(6.58)
4-8 hrs: Time Matched Baseline
73.24
(11.19)
73.24
(11.19)
73.24
(11.19)
73.81
(11.72)
73.81
(11.72)
4-8 hrs: Cycle Day 2 Change
9.24
(5.30)
7.56
(6.51)
6.50
(7.82)
12.82
(7.16)
8.89
(8.83)
8-12 hrs: Time Matched Baseline
76.22
(12.59)
76.22
(12.59)
76.22
(12.59)
76.95
(13.13)
76.95
(13.13)
8-12 hrs: Cycle Day 2 Change
1.91
(7.04)
-1.20
(6.52)
1.51
(5.34)
2.53
(5.55)
3.35
(8.48)
38. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
Description 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 Frame 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

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 10 10 10 9 9
0.5 hr: Time Matched Baseline
76.30
(9.89)
76.30
(9.89)
76.30
(9.89)
75.67
(10.27)
75.67
(10.27)
0.5 hr: Cycle Day 2 Change
-0.60
(4.17)
1.60
(5.23)
1.50
(8.34)
2.67
(9.62)
2.11
(5.42)
1 hr: Time Matched Baseline
73.50
(11.69)
73.50
(11.69)
73.50
(11.69)
74.44
(11.99)
74.44
(11.99)
1 hr: Cycle Day 2 Change
3.00
(6.09)
7.30
(8.19)
11.00
(10.09)
8.11
(7.85)
9.89
(9.98)
1.5 hrs: Time Matched Baseline
74.80
(12.25)
74.80
(12.25)
74.80
(12.25)
75.56
(12.74)
75.56
(12.74)
1.5 hrs: Cycle Day 2 Change
5.60
(4.93)
18.90
(12.72)
14.60
(14.21)
10.44
(7.75)
14.44
(5.39)
2 hrs: Time Matched Baseline
78.80
(15.30)
78.80
(15.30)
78.80
(15.30)
80.22
(15.51)
80.22
(15.51)
2 hrs: Cycle Day 2 Change
0.90
(8.13)
7.40
(5.91)
6.90
(7.03)
14.00
(22.92)
5.33
(9.50)
2.5 hrs: Time Matched Baseline
76.60
(13.43)
76.60
(13.43)
76.60
(13.43)
77.89
(13.57)
77.89
(13.57)
2.5 hrs: Cycle Day 2 Change
3.20
(7.79)
5.20
(6.71)
9.30
(12.28)
8.44
(7.70)
6.67
(11.70)
3 hrs: Time Matched Baseline
77.10
(15.53)
77.10
(15.53)
77.10
(15.53)
78.56
(15.73)
78.56
(15.73)
3 hrs: Cycle Day 2 Change
2.70
(9.01)
1.20
(10.81)
12.10
(14.56)
2.22
(8.77)
7.89
(12.23)
3.5 hrs: Time Matched Baseline
74.33
(15.84)
74.33
(15.84)
74.33
(15.84)
75.75
(16.31)
75.75
(16.31)
3.5 hrs: Cycle Day 2 Change
2.78
(6.85)
2.44
(5.17)
8.33
(10.10)
5.13
(10.52)
5.13
(13.82)
4 hrs: Time Matched Baseline
73.70
(15.98)
73.70
(15.98)
74.67
(16.64)
75.11
(16.27)
75.11
(16.27)
4 hrs: Cycle Day 2 Change
2.70
(6.63)
3.90
(9.45)
8.89
(13.59)
5.78
(8.76)
7.44
(13.53)
4.5 hrs: Time Matched Baseline
80.80
(13.73)
80.80
(13.73)
80.80
(13.73)
81.56
(14.34)
81.56
(14.34)
4.5 hrs: Cycle Day 2 Change
4.70
(7.02)
2.70
(8.03)
9.60
(15.24)
10.56
(10.86)
7.33
(9.64)
5 hrs: Time Matched Baseline
75.50
(10.21)
75.50
(10.21)
75.50
(10.21)
76.44
(10.36)
76.44
(10.36)
5 hrs: Cycle Day 2 Change
5.50
(11.45)
7.90
(13.87)
4.00
(10.65)
17.78
(14.81)
7.00
(15.26)
5.5 hrs: Time Matched Baseline
75.50
(10.10)
75.50
(10.10)
75.50
(10.10)
76.11
(10.52)
76.11
(10.52)
5.5 hrs: Cycle Day 2 Change
7.80
(11.69)
5.70
(11.79)
6.80
(11.12)
10.00
(11.22)
5.00
(13.22)
6 hrs: Time Matched Baseline
72.00
(11.11)
71.44
(11.63)
72.00
(11.11)
72.22
(11.76)
72.22
(11.76)
6 hrs: Cycle Day 2 Change
12.60
(15.07)
7.89
(9.57)
7.40
(10.36)
16.00
(13.87)
8.56
(8.79)
6.5 hrs: Time Matched Baseline
71.40
(11.04)
71.40
(11.04)
71.40
(11.04)
71.56
(11.70)
71.56
(11.70)
6.5 hrs: Cycle Day 2 Change
13.10
(7.53)
10.30
(10.47)
8.30
(11.73)
13.44
(10.57)
13.00
(15.73)
7 hrs: Time Matched Baseline
69.10
(13.47)
69.10
(13.47)
69.10
(13.47)
69.56
(14.20)
69.56
(14.20)
7 hrs: Cycle Day 2 Change
14.00
(6.39)
14.20
(14.20)
8.30
(7.04)
12.56
(4.42)
13.00
(9.75)
7.5 hrs: Time Matched Baseline
70.40
(14.42)
70.40
(14.42)
70.40
(14.42)
70.56
(15.28)
70.56
(15.28)
7.5 hrs: Cycle Day 2 Change
9.70
(9.23)
6.40
(8.76)
5.70
(7.24)
12.78
(9.76)
11.67
(14.98)
8 hrs: Time Matched Baseline
71.20
(13.72)
71.20
(13.72)
71.20
(13.72)
72.44
(13.94)
72.44
(13.94)
8 hrs: Cycle Day 2 Change
6.50
(7.04)
3.70
(5.14)
1.90
(6.57)
9.44
(8.11)
5.56
(8.71)
8.5 hrs: Time Matched Baseline
70.40
(13.63)
70.40
(13.63)
71.33
(14.12)
71.22
(14.19)
71.22
(14.19)
8.5 hrs: Cycle Day 2 Change
5.80
(9.61)
3.60
(7.18)
1.33
(8.44)
6.33
(7.92)
8.78
(10.35)
9 hrs: Time Matched Baseline
71.30
(15.10)
71.30
(15.10)
71.30
(15.10)
71.89
(15.89)
71.89
(15.89)
9 hrs: Cycle Day 2 Change
5.30
(12.45)
1.50
(9.65)
1.60
(10.27)
2.22
(13.89)
4.44
(11.26)
9.5 hrs: Time Matched Baseline
72.00
(14.83)
72.00
(14.83)
72.00
(14.83)
72.67
(15.57)
72.67
(15.57)
9.5 hrs: Cycle Day 2 Change
3.60
(9.38)
0.80
(9.20)
3.60
(12.33)
6.22
(7.51)
8.78
(10.17)
10 hrs: Time Matched Baseline
73.56
(12.82)
73.56
(12.82)
73.56
(12.82)
74.13
(13.58)
74.13
(13.58)
10 hrs: Cycle Day 2 Change
4.89
(12.20)
1.56
(8.00)
3.11
(5.88)
7.88
(9.60)
5.75
(12.13)
10.5 hrs: Time Matched Baseline
81.00
(12.12)
81.78
(12.59)
81.00
(12.12)
81.33
(12.81)
81.33
(12.81)
10.5 hrs: Cycle Day 2 Change
0.60
(10.84)
-3.89
(10.17)
-1.00
(5.77)
3.11
(11.19)
2.11
(9.51)
11 hrs: Time Matched Baseline
82.22
(17.10)
81.30
(16.38)
82.22
(17.10)
82.56
(16.86)
82.56
(16.86)
11 hrs: Cycle Day 2 Change
-4.33
(14.96)
-7.30
(14.62)
-2.67
(12.47)
-2.22
(15.21)
-3.56
(7.49)
11.5 hrs: Time Matched Baseline
81.60
(15.90)
81.60
(15.90)
81.60
(15.90)
82.78
(16.40)
82.78
(16.40)
11.5 hrs: Cycle Day 2 Change
-3.10
(8.70)
-5.80
(11.28)
0.20
(9.44)
-4.89
(9.52)
-3.56
(13.42)
12 hrs: Time Matched Baseline
78.45
(12.16)
78.45
(12.16)
78.45
(12.16)
78.94
(12.79)
78.94
(12.79)
12 hrs: Cycle Day 2 Change
2.25
(12.76)
0.65
(9.60)
4.40
(7.17)
2.44
(6.94)
2.78
(10.60)
39. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Pulse
Description 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 Frame Time-Matched Baseline (Placebo Cycle); Cycle Day 2

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 10 10 10 9 9
Time-Matched Baseline
75.01
(11.95)
75.01
(11.95)
75.01
(11.95)
75.78
(12.42)
75.78
(12.42)
Cycle Day 2 Change
4.55
(4.43)
4.14
(4.80)
5.70
(6.22)
7.49
(3.88)
6.55
(7.30)
40. Primary Outcome
Title Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Pulse
Description
Time Frame Follow-up Visit Day 32 (± 2 days)

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Mean (Standard Deviation) [bpm]
-2.5
(5.4)
41. Primary Outcome
Title Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Systolic Blood Pressure
Description
Time Frame Follow-up Visit Day 32 (± 2 days)

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Mean (Standard Deviation) [mmHg]
3.5
(7.3)
42. Primary Outcome
Title Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Diastolic Blood Pressure
Description
Time Frame Follow-up Visit Day 32 (± 2 days)

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Mean (Standard Deviation) [mmHg]
-0.5
(3.8)
43. Primary Outcome
Title Change From Study Baseline Over Time in Endothelial Function: Reactive Hyperemia Index (RHI)
Description 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.
Time Frame Study Baseline; Cycle Day 3: 0 h, 4 h, 12 h

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description Placebo taken once daily Day 1-Day 3 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 11 10 9 9
Study Baseline
2.21
(0.62)
2.21
(0.62)
2.28
(0.61)
2.21
(0.66)
2.28
(0.66)
2.28
(0.66)
Change at Cycle Day 3, 0 h
-0.08
(0.74)
-0.14
(0.91)
-0.13
(0.69)
0.31
(1.08)
0.20
(0.87)
-0.09
(0.87)
Change at Cycle Day 3, 4 h
-0.39
(0.65)
0.08
(0.99)
0.01
(0.75)
-0.15
(0.80)
-0.17
(0.98)
-0.06
(0.78)
Change at Cycle Day 3, 12 h
-0.03
(0.64)
0.33
(1.07)
0.29
(0.68)
0.07
(0.91)
0.17
(1.06)
0.37
(1.14)
44. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI
Description 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 Frame Time-matched Baseline (Placebo Cycle); Cycle Day 3: 0 h, 4 h, 12 h

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 10 9 9
Time-Matched Baseline, 0 h
2.13
(0.57)
2.15
(0.60)
2.24
(0.49)
2.28
(0.50)
2.28
(0.50)
Change at Cycle Day 3, 0 h
-0.07
(0.74)
0
(0.87)
0.28
(0.64)
0.19
(0.39)
-0.09
(1.01)
Time-Matched Baseline, 4 h
1.82
(0.26)
1.82
(0.26)
1.82
(0.27)
1.84
(0.27)
1.84
(0.27)
Change at Cycle Day 3, 4 h
0.47
(1.02)
0.40
(0.50)
0.25
(0.60)
0.26
(0.67)
0.37
(0.75)
Time-Matched Baseline, 12 h
2.18
(0.48)
2.18
(0.48)
2.16
(0.51)
2.12
(0.51)
2.12
(0.51)
Change at Cycle Day 3, 12 h
0.36
(0.77)
0.32
(0.39)
0.20
(0.54)
0.32
(0.66)
0.53
(0.68)
45. Primary Outcome
Title Change From Pre- to Post-Nitroglycerin Dose Assessment in Endothelial Function: RHI
Description 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.
Time Frame Follow-up Visit Day 32 (± 2 days)

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.
Arm/Group Title All Participants
Arm/Group Description Once-daily study drug for 18 days: placebo for 3 days and escalating doses of IW-1973 for 15 days (10 mg, 20 mg, 30 mg, 40 mg, 50 mg for 3 days each).
Measure Participants 11
Mean (Standard Deviation) [units on a scale]
-0.05
(0.37)
46. Primary Outcome
Title Change From Time-Matched Baseline (Placebo Cycle) in Platelet Function Assessments: Collagen/Epinephrine Time to Aggregation
Description 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 Frame Time-Matched Baseline (Placebo Cycle), Cycle Day 1, 0 h, Cycle Day 1, 4 h

Outcome Measure Data

Analysis Population Description
PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.
Arm/Group Title 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
Measure Participants 11 11 10 9 9
Time-Matched Baseline, 0 h
131.8
(60.6)
132.8
(63.8)
115.5
(28.7)
114.8
(30.3)
114.8
(30.3)
Change at Cycle Day 1, 0 h
-21.0
(54.6)
-38.7
(46.5)
-6.8
(25.0)
9.9
(47.4)
-4.2
(28.8)
Time-Matched Baseline, 4 h
121.3
(35.0)
121.3
(35.0)
115.0
(29.6)
114.6
(31.4)
114.6
(31.4)
Change at Cycle Day 1, 4 h
-3.8
(22.2)
-15.5
(40.2)
-7.4
(23.9)
14.2
(42.7)
-4.0
(32.4)

Adverse Events

Time Frame From first dose of study drug through end of trial (Day 46 [±3 days])
Adverse Event Reporting Description Treatment emergent adverse events (TEAEs) are presented. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.
Arm/Group Title Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Arm/Group Description Placebo taken once daily Day 1-Day 3 10 mg IW-1973 take once daily Day 4-Day 6 20 mg IW-1973 taken once daily Day 7-Day 9 30 mg IW-1973 taken once daily Day 10-Day 12 40 mg IW-1973 taken once daily Day 13-Day 15 50 mg IW-1973 taken once daily Day 16-Day 18
All Cause Mortality
Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/11 (0%) 0/11 (0%) 0/11 (0%) 0/10 (0%) 0/9 (0%) 0/9 (0%)
Serious Adverse Events
Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/11 (0%) 0/11 (0%) 0/11 (0%) 0/10 (0%) 0/9 (0%) 0/9 (0%)
Other (Not Including Serious) Adverse Events
Control 10 mg IW-1973 20 mg IW-1973 30 mg IW-1973 40 mg IW-1973 50 mg IW-1973
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/11 (27.3%) 3/11 (27.3%) 2/11 (18.2%) 4/10 (40%) 3/9 (33.3%) 2/9 (22.2%)
Cardiac disorders
Palpitations 0/11 (0%) 0/11 (0%) 0/11 (0%) 0/10 (0%) 0/9 (0%) 1/9 (11.1%)
Gastrointestinal disorders
Constipation 1/11 (9.1%) 0/11 (0%) 0/11 (0%) 1/10 (10%) 0/9 (0%) 0/9 (0%)
Diarrhoea 0/11 (0%) 0/11 (0%) 0/11 (0%) 0/10 (0%) 1/9 (11.1%) 1/9 (11.1%)
Dyspepsia 0/11 (0%) 0/11 (0%) 1/11 (9.1%) 0/10 (0%) 0/9 (0%) 0/9 (0%)
Nausea 0/11 (0%) 0/11 (0%) 0/11 (0%) 0/10 (0%) 1/9 (11.1%) 0/9 (0%)
Tongue eruption 1/11 (9.1%) 0/11 (0%) 0/11 (0%) 0/10 (0%) 0/9 (0%) 0/9 (0%)
Vomiting 0/11 (0%) 0/11 (0%) 0/11 (0%) 0/10 (0%) 1/9 (11.1%) 0/9 (0%)
Investigations
Blood pressure systolic decreased 0/11 (0%) 0/11 (0%) 1/11 (9.1%) 0/10 (0%) 0/9 (0%) 0/9 (0%)
Hepatic enzyme increased 0/11 (0%) 0/11 (0%) 0/11 (0%) 0/10 (0%) 0/9 (0%) 1/9 (11.1%)
Metabolism and nutrition disorders
Hypoglycaemia 0/11 (0%) 1/11 (9.1%) 0/11 (0%) 1/10 (10%) 1/9 (11.1%) 1/9 (11.1%)
Nervous system disorders
Headache 1/11 (9.1%) 2/11 (18.2%) 0/11 (0%) 2/10 (20%) 1/9 (11.1%) 2/9 (22.2%)
Dizziness 0/11 (0%) 0/11 (0%) 0/11 (0%) 1/10 (10%) 0/9 (0%) 1/9 (11.1%)
Somnolence 0/11 (0%) 1/11 (9.1%) 0/11 (0%) 0/10 (0%) 0/9 (0%) 0/9 (0%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion 0/11 (0%) 0/11 (0%) 0/11 (0%) 1/10 (10%) 0/9 (0%) 0/9 (0%)
Skin and subcutaneous tissue disorders
Skin irritation 0/11 (0%) 0/11 (0%) 1/11 (9.1%) 0/10 (0%) 0/9 (0%) 0/9 (0%)
Vascular disorders
Flushing 0/11 (0%) 0/11 (0%) 0/11 (0%) 1/10 (10%) 0/9 (0%) 0/9 (0%)
Orthostatic hypotension 0/11 (0%) 0/11 (0%) 0/11 (0%) 0/10 (0%) 1/9 (11.1%) 0/9 (0%)

Limitations/Caveats

No separate placebo control. 2 of 11 enrolled participants discontinued prematurely. Participants were confined, diet and activity controlled. Multiple dose-escalation design had no washout period between dose cycles. EndoPAT device was exploratory.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.

Results Point of Contact

Name/Title Senior Medical Director
Organization Cyclerion Therapeutics, Inc.
Phone 1-857-327-8778
Email info@cyclerion.com
Responsible Party:
Cyclerion Therapeutics
ClinicalTrials.gov Identifier:
NCT02906579
Other Study ID Numbers:
  • C1973-201
First Posted:
Sep 20, 2016
Last Update Posted:
Apr 16, 2020
Last Verified:
Apr 1, 2020