Phase 2
Completed N=11
A Phase 2 Trial of IW-1973, A Stimulator of Soluble Guanylate Cyclase (sGC), in Patients With Stable Type 2 Diabetes and Hypertension
Source: ClinicalTrials.gov NCT02906579 ↗Enrolled (actual)
11
Serious AEs
0.0%
Results posted
Apr 2020
Primary outcomePrimary: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to TEAEs — 3; 3; 2; 4 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to TEAEs |
3; 3; 2; 4; 3; 2 | — |
| PRIMARY Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19) |
141.7; -43.3; 116.82; -26.45; 44.36; -5.91 | — |
| PRIMARY Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32) |
183.1; -1.9; 154.27; 11.00; 48.18; -2.09 | — |
| PRIMARY Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase at Discharge Day (Day 19) |
28.3; -7.9; 135.7; -27.4 | — |
| PRIMARY Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in GGT and Lactate Dehydrogenase at Follow-Up (Day 32) |
53.6; 17.5; 171.6; 8.5 | — |
| PRIMARY Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Discharge Day (Day 19) |
7.27; -0.40 | — |
| PRIMARY Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Follow-Up (Day 32) |
7.54; -0.14 | — |
| PRIMARY Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Discharge Day (Day 19) |
17.45; -0.05 | — |
| PRIMARY Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Follow-Up (Day 32) |
23.81; 6.31 | — |
| PRIMARY Change From Time-Matched Baseline in Fasting Blood Glucose on Day 2 of Each Dose Cycle |
142.3; 142.3; 144.1; 147.7; 147.7; -12.0 | — |
| PRIMARY Change From Time-Matched Baseline in Serum Insulin on Day 2 of Each Dose Cycle |
17.35; 17.35; 17.37; 14.32; 14.32; 0.20 | — |
| PRIMARY Number of Participants With Notable Changes in Post Baseline Vital Signs Values |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Notable Post Baseline Orthostatic Vital Signs Values |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Change From Baseline Over Time in Respiratory Rate |
-0.7; -1.5 | — |
| PRIMARY Change From Baseline Over Time in Temperature |
0.12; -0.03 | — |
| PRIMARY Change From Baseline Over Time in Weight |
-3.47; -1.40 | — |
| PRIMARY Number of Participants With Clinically Significant Findings or Shifts in Baseline in Electrocardiograms (ECGs) |
— | — |
| PRIMARY Number of Participants With Clinically Significant Findings or Shifts in Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Change From Study Baseline Over Time in Supine Pulse |
72.0; 72.0; 72.0; 72.7; 73.2; 73.2 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse |
66.5; 66.5; 66.7; 67.0; 67.0; -1.1 | — |
| PRIMARY Change From Study Baseline Over Time in Supine Systolic Blood Pressure |
136.3; 136.3; 136.3; 133.9; 132.9; 132.9 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure |
127.4; 127.4; 126.3; 125.2; 125.2; -0.9 | — |
| PRIMARY Change From Study Baseline Over Time in Supine Diastolic Blood Pressure |
80.4; 80.4; 80.4; 79.9; 78.2; 78.2 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure |
77.1; 77.1; 77.0; 75.7; 75.7; -1.1 | — |
| PRIMARY Orthostatic Pulse Over Time |
9.7; 11.6; 11.0; 11.9; 11.0; 10.4 | — |
| PRIMARY Orthostatic Systolic Blood Pressure Over Time |
4.4; 3.7; 5.9; 4.0; 3.4; 4.2 | — |
| PRIMARY Orthostatic Diastolic Blood Pressure Over Time |
7.0; 9.3; 8.1; 5.7; 8.3; 7.4 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure |
125.67; 125.67; 125.67; 125.72; 125.72; -5.18 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure |
140.30; 140.30; 140.30; 138.22; 138.22; -4.90 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure |
126.27; 126.27; 126.27; 125.45; 125.45; -4.42 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure |
75.59; 75.59; 75.59; 74.94; 74.94; -2.96 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure |
87.90; 87.90; 87.90; 86.44; 86.44; -2.40 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Diastolic Blood Pressure |
75.71; 75.71; 75.71; 74.51; 74.51; -1.26 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure |
92.61; 92.61; 92.61; 92.21; 92.21; -3.93 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure |
104.50; 104.50; 104.50; 102.00; 102.00; -3.70 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Mean Arterial Pressure |
92.64; 92.64; 92.64; 91.55; 91.55; -2.33 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse |
75.61; 75.61; 75.61; 76.59; 76.59; 2.49 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse |
76.30; 76.30; 76.30; 75.67; 75.67; -0.60 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Pulse |
75.01; 75.01; 75.01; 75.78; 75.78; 4.55 | — |
| PRIMARY Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Pulse |
-2.5 | — |
| PRIMARY Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Systolic Blood Pressure |
3.5 | — |
| PRIMARY Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Diastolic Blood Pressure |
-0.5 | — |
| PRIMARY Change From Study Baseline Over Time in Endothelial Function: Reactive Hyperemia Index (RHI) |
2.21; 2.21; 2.28; 2.21; 2.28; 2.28 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI |
2.13; 2.15; 2.24; 2.28; 2.28; -0.07 | — |
| PRIMARY Change From Pre- to Post-Nitroglycerin Dose Assessment in Endothelial Function: RHI |
-0.05 | — |
| PRIMARY Change From Time-Matched Baseline (Placebo Cycle) in Platelet Function Assessments: Collagen/Epinephrine Time to Aggregation |
131.8; 132.8; 115.5; 114.8; 114.8; -21.0 | — |
Eligibility Criteria
Inclusion Criteria
- Patient is ambulatory male or female
- Patient's body mass index score is >20 and 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
Data sourced from ClinicalTrials.gov (NCT02906579). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.