Clinical trial NCT03091920: Trial of IW-1973, A Stimulator of Soluble Guanylate Cyclase (sGC) in Patients With Stable Type 2 Diabetes and Hypertension
Official title: A Phase 2 Study to Compare the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of 2 Dose Regimens of IW-1973 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: 2017-03-27
Enrollment: 26
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

* Patient is ambulatory male or female
* Patient's body mass index score is \> 20 and \< 40 kg/m\^2 at the Screening Visit
* Women of childbearing potential must have a negative pregnancy test at the time of screening and check-in and must agree to use protocol-specified contraception throughout the duration of the study
* Patient's health is stable with no clinically significant findings on physical examination
* Patient has type 2 (ie, adult onset) diabetes mellitus diagnosed by a physician or nurse practitioner \> 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

Primary outcomes:
measure: Change From Study Baseline Over Time in Supine Systolic Blood Pressure
timeFrame: Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42
measure: Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
timeFrame: Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42
measure: Change From Study Baseline Over Time in Supine Pulse
timeFrame: Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42
measure: Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
timeFrame: Baseline, Days 1-14, Day 15, 21, 42
measure: Orthostatic Systolic Blood Pressure Over Time
timeFrame: Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM
measure: Orthostatic Diastolic Blood Pressure Over Time
timeFrame: Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM
measure: Orthostatic Pulse Over Time
timeFrame: Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM
measure: Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure
timeFrame: Time Matched Baseline (Day -1), Days 1, 7, and 14
measure: Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
timeFrame: Time Matched Baseline (Day -1), Days 1, 7, and 14
measure: Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure
timeFrame: Time Matched Baseline (Day -1), Days 1, 7, and 14
measure: Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
timeFrame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
measure: Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure
timeFrame: Time Matched Baseline (Day -1), Days 1, 7, and 14
measure: Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure
timeFrame: Time Matched Baseline (Day -1), Days 1, 7, and 14
measure: Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure
timeFrame: Time Matched Baseline (Day -1), Days 1, 7, and 14
measure: Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
timeFrame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
measure: Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure
timeFrame: Time Matched Baseline (Day -1), Days 1, 7, and 14
measure: Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure
timeFrame: Time Matched Baseline (Day -1), Days 1, 7, and 14
measure: Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure
timeFrame: Time Matched Baseline (Day -1), Days 1, 7, and 14
measure: Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
timeFrame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
measure: Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse
timeFrame: Time Matched Baseline (Day -1), Days 1, 7, and 14
measure: Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse
timeFrame: Time Matched Baseline (Day -1), Days 1, 7, and 14
measure: Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse
timeFrame: Time Matched Baseline (Day -1), Days 1, 7, and 14
measure: Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
timeFrame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
measure: Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13
timeFrame: Baseline, Day 13 predose AM
measure: Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay
timeFrame: Baseline, Day 8, Day 14
measure: Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
timeFrame: Baseline, Day 8, Day 14
measure: Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay
timeFrame: Study Baseline (Day 1 predose), Day 8 (predose AM), Day 14 (predose AM)
measure: Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay
timeFrame: Study Baseline (Day 1 predose), Day 8 (pre AM dose), Day 14 (pre AM dose)
measure: Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin
timeFrame: Study baseline (defined as the last non-missing assessment before the first administration of study drug), Day 8, pre-AM dose, Day 15
measure: IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7
timeFrame: Days 1 and 7 (AM): 1, 3, and 6 hours postdose
measure: IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7
timeFrame: Days 1 and 7 (AM): 1, 3, and 6 hours postdose
measure: IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7
timeFrame: Days 1 and 7 (AM): 1, 3, and 6 hours postdose
measure: IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7
timeFrame: Days 1 and 7: predose; Day 2 (BID AM): predose; Day 6 (BID PM/QD): predose
measure: 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
timeFrame: Day 8 and 14: 1, 3, 6h (± 5 min) postdose
measure: IW-1973 Pharmacokinetics: AUCtau on Day 14
timeFrame: Day 14: 1, 3, 6h (± 5 min) postdose
measure: IW-1973 Pharmacokinetics: Tmax on Days 8 and 14
timeFrame: Day 8 and 14: 1, 3, 6h (± 5 min) postdose
measure: IW-1973 Pharmacokinetics: Cmax on Days 8 and 14
timeFrame: Day 8 and 14: 1, 3, 6h (± 5 min) postdose
measure: IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14
timeFrame: Days 13 and 14: predose
measure: IW-1973 Pharmacokinetics: Apparent Total Body Clearance (CL/F) on Day 14
timeFrame: Day 14: 1, 3, 6h (± 5 min) postdose
measure: IW-1973 Pharmacokinetics: Apparent Volume of Distribution During the Terminal Phase (Vz/F) on Day 14
timeFrame: Day 14: 1, 3, 6h (± 5 min) postdose
measure: IW-1973 Pharmacokinetics: Apparent Terminal Elimination Phase Half-Life (t1/2)
timeFrame: Day 14 (final dose) time points 12 hours, 24 hours, 7 days after final dose (Day 21), and 28 days after final dose(Day 42)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
timeFrame: From first dose of study drug to End of Trial Visit (42 [± 3] days)
measure: Number of Participants With Clinically Meaningful Postbaseline Laboratory Test Results
timeFrame: From first dose of study drug to End of Trial Visit (42 [± 3] days)
measure: Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
timeFrame: From first dose of study drug to End of Trial Visit (42 [± 3] days)
measure: Number of Participants With Clinically Significant Post-Randomization Physical Examination Findings
timeFrame: Post-randomization to End of Trial Visit (42 [± 3] days)
measure: Number of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results
timeFrame: From first dose of study drug to End of Trial Visit (42 [± 3] days)
measure: Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Study Baseline, Day 15/Discharge, Day 42/End of Trial
Secondary outcomes:
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: ProSciento, Inc.
state: California
Study officials:
References:
citation: Hanrahan JP, Seferovic JP, Wakefield JD, Wilson PJ, Chickering JG, Jung J, Carlson KE, Zimmer DP, Frelinger AL 3rd, Michelson AD, Morrow L, Hall M, Currie MG, Milne GT, Profy AT. An exploratory, randomised, placebo-controlled, 14 day trial of the soluble guanylate cyclase stimulator praliciguat in participants with type 2 diabetes and hypertension. Diabetologia. 2020 Apr;63(4):733-743. doi: 10.1007/s00125-019-05062-x. Epub 2019 Dec 19.