Clinical trial NCT02906579: A Phase 2 Trial of IW-1973, A Stimulator of Soluble Guanylate Cyclase (sGC), in Patients With Stable Type 2 Diabetes and Hypertension
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Hypertension
Lead sponsor: Cyclerion Therapeutics
Sponsor class: INDUSTRY
First posted: 2016-09-20
Enrollment: 11
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to TEAEs
timeFrame: From first dose of study drug through end of trial (Day 46 [±3 days])
measure: Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)
timeFrame: Baseline, Day 19
measure: Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)
timeFrame: Baseline, Day 32
measure: Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase at Discharge Day (Day 19)
timeFrame: Baseline, Day 19
measure: Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in GGT and Lactate Dehydrogenase at Follow-Up (Day 32)
timeFrame: Baseline, Day 32
measure: Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Discharge Day (Day 19)
timeFrame: Baseline, Day 19
measure: Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Follow-Up (Day 32)
timeFrame: Baseline, Day 32
measure: Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Discharge Day (Day 19)
timeFrame: Baseline, Day 19
measure: Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Follow-Up (Day 32)
timeFrame: Baseline, Day 32
measure: Change From Time-Matched Baseline in Fasting Blood Glucose on Day 2 of Each Dose Cycle
timeFrame: Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)
measure: Change From Time-Matched Baseline in Serum Insulin on Day 2 of Each Dose Cycle
timeFrame: Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)
measure: Number of Participants With Notable Changes in Post Baseline Vital Signs Values
timeFrame: Up to Day 32
measure: Number of Participants With Notable Post Baseline Orthostatic Vital Signs Values
timeFrame: Up to Day 32
measure: Change From Baseline Over Time in Respiratory Rate
timeFrame: Baseline, Day 19, Day 32
measure: Change From Baseline Over Time in Temperature
timeFrame: Baseline, Day 19, Day 32
measure: Change From Baseline Over Time in Weight
timeFrame: Baseline, Day 19, Day 32
measure: Number of Participants With Clinically Significant Findings or Shifts in Baseline in Electrocardiograms (ECGs)
timeFrame: Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19
measure: Number of Participants With Clinically Significant Findings or Shifts in Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF)
timeFrame: Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19
measure: Change From Study Baseline Over Time in Supine Pulse
timeFrame: 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
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
timeFrame: 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
measure: Change From Study Baseline Over Time in Supine Systolic Blood Pressure
timeFrame: 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
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
timeFrame: 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
measure: Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
timeFrame: 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
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
timeFrame: 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
measure: Orthostatic Pulse Over Time
timeFrame: 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
measure: Orthostatic Systolic Blood Pressure Over Time
timeFrame: 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
measure: Orthostatic Diastolic Blood Pressure Over Time
timeFrame: 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
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure
timeFrame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
timeFrame: 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
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
timeFrame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure
timeFrame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
timeFrame: 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
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Diastolic Blood Pressure
timeFrame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure
timeFrame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
timeFrame: 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
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Mean Arterial Pressure
timeFrame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse
timeFrame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
timeFrame: 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
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Pulse
timeFrame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2
measure: Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Pulse
timeFrame: Follow-up Visit Day 32 (± 2 days)
measure: Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Systolic Blood Pressure
timeFrame: Follow-up Visit Day 32 (± 2 days)
measure: Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Diastolic Blood Pressure
timeFrame: Follow-up Visit Day 32 (± 2 days)
measure: Change From Study Baseline Over Time in Endothelial Function: Reactive Hyperemia Index (RHI)
timeFrame: Study Baseline; Cycle Day 3: 0 h, 4 h, 12 h
measure: Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI
timeFrame: Time-matched Baseline (Placebo Cycle); Cycle Day 3: 0 h, 4 h, 12 h
measure: Change From Pre- to Post-Nitroglycerin Dose Assessment in Endothelial Function: RHI
timeFrame: Follow-up Visit Day 32 (± 2 days)
measure: Change From Time-Matched Baseline (Placebo Cycle) in Platelet Function Assessments: Collagen/Epinephrine Time to Aggregation
timeFrame: Time-Matched Baseline (Placebo Cycle), Cycle Day 1, 0 h, Cycle Day 1, 4 h
Secondary outcomes:
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: ICON Early Phase Unit
state: Texas
Study officials:
References: