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

NCT02906579 | Completed Phase 2 Results

• 1 other identifier: C1973-201
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2; Hypertension

Outcome Measures

Primary Outcomes (46)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to TEAEs

  An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with study treatment. An SAE is defined as any AE occurring at any dose that results in any of the following outcomes: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical events. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.

  From first dose of study drug through end of trial (Day 46 [±3 days])

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

  Study baseline is defined as the Day -1 assessment.

  Baseline, Day 19

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

  Study baseline is defined as the Day -1 assessment.

  Baseline, Day 32

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

  Study baseline is defined as the Day -1 assessment.

  Baseline, Day 19

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

  Study baseline is defined as the Day -1 assessment.

  Baseline, Day 32

• Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Discharge Day (Day 19)

  Study baseline is defined as the Day -1 assessment.

  Baseline, Day 19

• Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Follow-Up (Day 32)

  Study baseline is defined as the Day -1 assessment.

  Baseline, Day 32

• Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Discharge Day (Day 19)

  Study baseline is defined as the Day -1 assessment.

  Baseline, Day 19

• Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Follow-Up (Day 32)

  Study baseline is defined as the Day -1 assessment.

  Baseline, Day 32

• Change From Time-Matched Baseline in Fasting Blood Glucose on Day 2 of Each Dose Cycle

  Time-matched baseline is defined as the corresponding assessment on Day 2 of the placebo cycle. Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

  Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)

• Change From Time-Matched Baseline in Serum Insulin on Day 2 of Each Dose Cycle

  Time-matched baseline is defined as the corresponding assessment on Day 2 of the placebo cycle. Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

  Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)

• Number of Participants With Notable Changes in Post Baseline Vital Signs Values

  Supine systolic blood pressure (SSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Supine Diastolic Blood Pressure (SDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Supine pulse rate (SPR): ≥ 110 beats per minute (bpm) and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm. Standing systolic blood pressure (StSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Standing Diastolic Blood Pressure (StDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Standing pulse rate (StPR): ≥ 110 beats per minute (bpm) and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm.

  Up to Day 32

• Number of Participants With Notable Post Baseline Orthostatic Vital Signs Values

  Systolic blood pressure (SBP): Decrease of \> 20 mmHg from supine to standing Diastolic blood pressure (DBP): Decrease of \> 10 mmHg from supine to standing Pulse rate (PR): Increase of \> 20 bpm from supine to standing.

  Up to Day 32

• Change From Baseline Over Time in Respiratory Rate

  Baseline, Day 19, Day 32

• Change From Baseline Over Time in Temperature

  Baseline, Day 19, Day 32

• Change From Baseline Over Time in Weight

  Baseline, Day 19, Day 32

• Number of Participants With Clinically Significant Findings or Shifts in Baseline in Electrocardiograms (ECGs)

  Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19

• Number of Participants With Clinically Significant Findings or Shifts in Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF)

  Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19

• Change From Study Baseline Over Time in Supine Pulse

  Study baseline is defined as the Day -1 assessment.

  Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h

• Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse

  Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h

• Change From Study Baseline Over Time in Supine Systolic Blood Pressure

  Study baseline is defined as the Day -1 assessment.

  Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h

• Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure

  Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h

• Change From Study Baseline Over Time in Supine Diastolic Blood Pressure

  Study baseline is defined as the Day -1 assessment.

  Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h

• Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure

  Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h

• Orthostatic Pulse Over Time

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

  Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h

• Orthostatic Systolic Blood Pressure Over Time

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

  Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h

• Orthostatic Diastolic Blood Pressure Over Time

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

  Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h

• Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure

  Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs

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

  Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs

• Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure

  Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 2

• Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure

  Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs

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

  Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs

• Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Diastolic Blood Pressure

  Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 2

• Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure

  Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs

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

  Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs

• Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Mean Arterial Pressure

  Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 2

• Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse

  Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs

• Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse

  Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs

• Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Pulse

  Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle); Cycle Day 2

• Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Pulse

  Follow-up Visit Day 32 (± 2 days)

• Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Systolic Blood Pressure

  Follow-up Visit Day 32 (± 2 days)

• Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Diastolic Blood Pressure

  Follow-up Visit Day 32 (± 2 days)

• Change From Study Baseline Over Time in Endothelial Function: Reactive Hyperemia Index (RHI)

  Study baseline is defined as the Day -1 assessment. Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction.

  Study Baseline; Cycle Day 3: 0 h, 4 h, 12 h

• Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI

  Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction. Baseline is designated per protocol as Day 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 3 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-matched Baseline (Placebo Cycle); Cycle Day 3: 0 h, 4 h, 12 h

• Change From Pre- to Post-Nitroglycerin Dose Assessment in Endothelial Function: RHI

  Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction.

  Follow-up Visit Day 32 (± 2 days)

• Change From Time-Matched Baseline (Placebo Cycle) in Platelet Function Assessments: Collagen/Epinephrine Time to Aggregation

  Time-matched baseline is defined as the corresponding assessment on Day 1 of the placebo cycle. Platelet function assessment used the PFA-100® instrument to evaluate collagen/epinephrine time to aggregation. Baseline is designated per protocol as Day 1 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 of each IW-1973 dose at given time point are presented as the second row of data.

  Time-Matched Baseline (Placebo Cycle), Cycle Day 1, 0 h, Cycle Day 1, 4 h

Study Arms (1)

IW-1973

EXPERIMENTAL

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

Interventions

Matching Placebo DRUG

IW-1973

IW-1973 DRUG

IW-1973

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cyclerion Therapeutics: lead

Study Sites (1)

ICON Early Phase Unit

San Antonio, Texas, 78209, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypertension

Interventions

praliciguat

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases

Limitations and 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.

Results Point of Contact

• Title: Senior Medical Director
• Organization: Cyclerion Therapeutics, Inc.

info@cyclerion.com

1-857-327-8778

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2016
• First Posted: September 20, 2016
• Study Start: September 1, 2016
• Primary Completion: March 17, 2017
• Study Completion: March 17, 2017
• Last Updated: April 16, 2020
• Results First Posted: April 16, 2020

Record last verified: 2020-04

Locations

US (1)