Phase 2
Completed N=26
Trial of IW-1973, A Stimulator of Soluble Guanylate Cyclase (sGC) in Patients With Stable Type 2 Diabetes and Hypertension
Source: ClinicalTrials.gov NCT03091920 ↗Enrolled (actual)
26
Serious AEs
3.9%
Results posted
Aug 2020
Primary outcomePrimary: Change From Study Baseline Over Time in Supine Systolic Blood Pressure — 130.2; 120.1; 128.6; -6.8 mmHg
Summary
To compare the safety, tolerability, pharmacokinetic (PK) profile, and pharmacodynamic (PD) effects of 2 treatment regimens of IW-1973 tablet (40 mg per day) administered orally for 2 weeks to patients with stable type 2 diabetes mellitus and hypertension.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Study Baseline Over Time in Supine Systolic Blood Pressure |
130.2; 120.1; 128.6; -6.8; -7.7; -6.2 | — |
| PRIMARY Change From Study Baseline Over Time in Supine Diastolic Blood Pressure |
80.3; 75.5; 74.8; -3.1; -5.7; -5.1 | — |
| PRIMARY Change From Study Baseline Over Time in Supine Pulse |
70.3; 70.3; 70.0; 1.0; 7.2; 10.2 | — |
| PRIMARY Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time |
33.3; 80.0; 60.0; 100; 100; 100 | — |
| PRIMARY Orthostatic Systolic Blood Pressure Over Time |
-0.8; 2.0; 5.6; 0.3; 2.9; 2.3 | — |
| PRIMARY Orthostatic Diastolic Blood Pressure Over Time |
1.8; 3.3; 6.3; -0.5; 3.6; 5.5 | — |
| PRIMARY Orthostatic Pulse Over Time |
9.2; 9.2; 10.2; 4.7; 10.9; 9.5 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure |
132.34; 126.40; 129.00; 127.70; -0.60; -3.92 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure |
136.99; 130.64; 132.28; -0.74; -7.80; -4.93 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure |
126.76; 121.77; 125.26; 0.11; -0.11; -1.50 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure |
134.45; 128.18; 128.38; 136.10; 130.04; 132.53 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure |
96.44; 90.27; 91.14; 90.71; -0.68; -2.80 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure |
100.09; 93.31; 94.00; -0.20; -5.07; -5.22 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure |
91.93; 86.85; 87.77; -0.39; -0.84; -1.10 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure |
98.10; 91.52; 91.16; 98.92; 92.27; 93.98 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure |
77.37; 71.57; 71.50; 71.53; -1.73; -2.53 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure |
80.71; 74.31; 74.20; -0.88; -4.28; -4.47 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure |
73.42; 68.44; 68.36; -2.02; -1.03; -1.46 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure |
78.96; 72.48; 71.58; 79.85; 73.96; 73.79 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse |
75.08; 72.81; 75.40; 74.10; -0.90; 2.29 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse |
76.81; 75.98; 78.18; 0.14; 2.30; 4.23 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse |
73.43; 69.62; 72.54; -2.01; 2.29; 0.93 | — |
| PRIMARY Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse |
73.52; 73.89; 76.46; 77.65; 76.88; 79.91 | — |
| PRIMARY Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13 |
2.327; 1.918; 1.683; 1.807; 0.282; -0.006 | — |
| PRIMARY Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay |
0; 0; 0; 5; 10; 10 | — |
| PRIMARY Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay |
2; 5; 6; 3; 5; 4 | — |
| PRIMARY Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay |
304.0; 283.6; 294.4; -9.4; 8.2; -0.7 | — |
| PRIMARY Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay |
571.4; 557.4; 524.6; -8.0; -16.2; 18.7 | — |
| PRIMARY Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin |
7.350; 6.646; 7.187; 6.962; -4.284; -27.473 | — |
| PRIMARY IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7 |
362; 339; 1190; 795; 2200 | — |
| PRIMARY IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7 |
73.8; 47.8; 181; 117; 242 | — |
| PRIMARY IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7 |
1.0; 3.0; 2.0; 1.0; 1.0 | — |
| PRIMARY IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7 |
11.6; 19.6; 15.6; 21.0; 48.4; 53.7 | — |
| PRIMARY IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Plasma Concentration (AUClast) on Days 8 and 14 |
1210; 1540; 17100; 23600 | — |
| PRIMARY IW-1973 Pharmacokinetics: AUCtau on Day 14 |
2080; 2910 | — |
| PRIMARY IW-1973 Pharmacokinetics: Tmax on Days 8 and 14 |
1.0; 1.0; 1.0; 3.0 | — |
| PRIMARY IW-1973 Pharmacokinetics: Cmax on Days 8 and 14 |
198; 229; 181; 250 | — |
| PRIMARY IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14 |
56.8; 82.4; 65.7; 90.7 | — |
| PRIMARY IW-1973 Pharmacokinetics: Apparent Total Body Clearance (CL/F) on Day 14 |
20.0; 14.7 | — |
| PRIMARY IW-1973 Pharmacokinetics: Apparent Volume of Distribution During the Terminal Phase (Vz/F) on Day 14 |
5570; 3880 | — |
| PRIMARY IW-1973 Pharmacokinetics: Apparent Terminal Elimination Phase Half-Life (t1/2) |
197; 183 | — |
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs |
5; 6; 8; 0; 1; 0 | — |
| PRIMARY Number of Participants With Clinically Meaningful Postbaseline Laboratory Test Results |
0; 1; 1 | — |
| PRIMARY Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values |
0; 0; 0; 0; 1; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Post-Randomization Physical Examination Findings |
0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results |
0; 0; 0 | — |
| PRIMARY Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR) |
103.045; 89.014; 80.373; 0.158; -2.232; 1.663 | — |
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, is on a stable glycemic control medication, and protocol specified hemoglobin (Hb)A1c values at the Screening Visit
- Patient has hypertension diagnosed by a physician or nurse practitioner > 6 months before the Screening Visit, and blood pressure (BP) within the protocol's acceptable range
- Patients must be on a stable regimen for hypertension control that includes an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), stable for 28 days
- 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 sGC stimulator, could increase the risk of hypotension
- Patient has evidence of severe or active end-organ damage
- Patient is an active smoker or has used any nicotine-containing products (cigarettes, e-cigarettes, vape pens, cigars, chewing tobacco, gum, patches) during the 6 months before Check-in. Use of nicotine is excluded during the study until after the End of Trial Visit.
- Other exclusion criteria per protocol
Data sourced from ClinicalTrials.gov (NCT03091920). 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.