Diabetes Mellitus, Type 2Phase 2NCT03091920

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

A Phase 2 study testing IW-1973 in people with Diabetes Mellitus, Type 2 and Hypertension, run by Cyclerion Therapeutics at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 30 to 75 years
Conditions the study is for: Diabetes Mellitus, Type 2, Hypertension
What is being tested?: IW-1973
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 26 participants
Where: 1 siteUnited States
Study dates: 28 Feb 2017to 3 Aug 2017
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 30 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

ProSciento, Inc.
Chula Vista, California, 91911

Other trials in United States

About this study

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

Conditions: Diabetes Mellitus, Type 2, Hypertension
Being tested: IW-1973, Placebo
Medical subject headings: Diabetes Mellitus, Type 2, Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IW-1973Drug
Oral Tablet
PlaceboDrug
Oral Tablet

Study groups in NCT03091920
Study group	Role	What they receive
IW-1973 QD/QD	Experimental	On Days 1-14: IW-1973 40 mg taken once daily (QD) in morning (AM) and placebo taken QD at night (PM). Receives: Drug: IW-1973; Drug: Placebo
IW-1973 BID (Twice Daily)/QD	Experimental	On Days 1-7: IW-1973 20 mg taken in AM and IW-1973 20 mg taken in PM. On Days 8-14: IW-1973 40 mg taken QD in AM and placebo taken QD in PM. Receives: Drug: IW-1973; Drug: Placebo
Placebo	Placebo comparator	On Days 1-14: Placebo taken in AM and in PM. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Measured: 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
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Measured: 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
Change From Study Baseline Over Time in Supine Pulse
Measured: 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
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Measured: Baseline, Days 1-14, Day 15, 21, 42
Orthostatic Systolic Blood Pressure Over Time
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Measured: 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
Orthostatic Diastolic Blood Pressure Over Time
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Measured: 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
Orthostatic Pulse Over Time
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Measured: 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
Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Measured: Time Matched Baseline (Day -1), Days 1, 7, and 14
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Measured: Time Matched Baseline (Day -1), Days 1, 7, and 14
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Measured: Time Matched Baseline (Day -1), Days 1, 7, and 14
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Measured: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Measured: Time Matched Baseline (Day -1), Days 1, 7, and 14
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Measured: Time Matched Baseline (Day -1), Days 1, 7, and 14
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Measured: Time Matched Baseline (Day -1), Days 1, 7, and 14
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Measured: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Measured: Time Matched Baseline (Day -1), Days 1, 7, and 14
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Measured: Time Matched Baseline (Day -1), Days 1, 7, and 14
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Measured: Time Matched Baseline (Day -1), Days 1, 7, and 14
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Measured: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Measured: Time Matched Baseline (Day -1), Days 1, 7, and 14
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Measured: Time Matched Baseline (Day -1), Days 1, 7, and 14
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Measured: Time Matched Baseline (Day -1), Days 1, 7, and 14
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Measured: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13
RHI is a measure of the extent of vessel dilatation and augmentation in vascular blood flow after a prespecified period of flow interruption. RHI is determined as the ratio of the post-to-pre- occlusion peripheral arterial tonometry amplitude of the tested (occluded) arm, divided by the post to-pre-occlusion ratio of the control arm. RHI values >1.67 indicate normal endothelial function, while values ≤1.67 indicate endothelial dysfunction.
Measured: Baseline, Day 13 predose AM
Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay
Platelet reactivity, as measured by VerifyNow PRU assay, and presented as number of participants with < 180 PRU or ≥ 180 PRU post-baseline (Days 8 and 14), by baseline category.
The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values < 180 units indicate impairment of platelet aggregation.
Measured: Baseline, Day 8, Day 14
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
Platelet reactivity, as measured by VerifyNow ARU assay, and presented as number of participants with ≤ 549 ARU or > 549 ARU post-baseline (Days 8 and 14), by baseline category.
Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the glycoprotein (GP)IIb/IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU.
Measured: Baseline, Day 8, Day 14
Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay
The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values <180 PRU indicate impairment of platelet aggregation.
Measured: Study Baseline (Day 1 predose), Day 8 (predose AM), Day 14 (predose AM)
Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay
Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the GPIIb IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU.
Measured: Study Baseline (Day 1 predose), Day 8 (pre AM dose), Day 14 (pre AM dose)
Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin
Blood samples were taken for fasting glucose and insulin levels. From these results, insulin resistance was then estimated using the updated homeostasis model assessment method for insulin resistance (HOMA-IR) computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Typically a cutoff of HOMA-IR for identifying those with insulin resistance is 2.5.
Measured: Study baseline (defined as the last non-missing assessment before the first administration of study drug), Day 8, pre-AM dose, Day 15
IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7
Equivalent to AUC from time 0 to the last measurable concentration (AUClast), with time of last measurable concentration (Tlast)=12 hours for BID dosing and Tlast=24 hours for QD dosing.
Measured: Days 1 and 7 (AM): 1, 3, and 6 hours postdose
IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7
Measured: Days 1 and 7 (AM): 1, 3, and 6 hours postdose
IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7
Measured: Days 1 and 7 (AM): 1, 3, and 6 hours postdose
IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7
Measured: Days 1 and 7: predose; Day 2 (BID AM): predose; Day 6 (BID PM/QD): predose
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
Measured: Day 8 and 14: 1, 3, 6h (± 5 min) postdose
IW-1973 Pharmacokinetics: AUCtau on Day 14
Measured: Day 14: 1, 3, 6h (± 5 min) postdose
IW-1973 Pharmacokinetics: Tmax on Days 8 and 14
Measured: Day 8 and 14: 1, 3, 6h (± 5 min) postdose
IW-1973 Pharmacokinetics: Cmax on Days 8 and 14
Measured: Day 8 and 14: 1, 3, 6h (± 5 min) postdose
IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14
Measured: Days 13 and 14: predose
IW-1973 Pharmacokinetics: Apparent Total Body Clearance (CL/F) on Day 14
Measured: Day 14: 1, 3, 6h (± 5 min) postdose
IW-1973 Pharmacokinetics: Apparent Volume of Distribution During the Terminal Phase (Vz/F) on Day 14
Measured: Day 14: 1, 3, 6h (± 5 min) postdose
IW-1973 Pharmacokinetics: Apparent Terminal Elimination Phase Half-Life (t1/2)
Measured: 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)
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), 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. AEs of clinical interest (AECI) included those related to bleeding and to hypotension. Study drug causality as assessed by the Investigator who was blinded to study drug assignment.
Measured: From first dose of study drug to End of Trial Visit (42 [± 3] days)
Number of Participants With Clinically Meaningful Postbaseline Laboratory Test Results
Measured: From first dose of study drug to End of Trial Visit (42 [± 3] days)
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate 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 heart rate (SHR): ≥ 110 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 heart rate (StHR): ≥ 110 bpm and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm.
Orthostatic systolic blood pressure (SBP): ↓ > 20 mmHg from supine to standing.
Orthostatic diastolic blood pressure (DBP): ↓ > 15 mmHg from supine to standing.
Orthostatic HR: ↓ > 30 bpm from supine to standing.
Measured: From first dose of study drug to End of Trial Visit (42 [± 3] days)
Number of Participants With Clinically Significant Post-Randomization Physical Examination Findings
Physical examinations included examination and assessment of the following: general appearance, lymph nodes, skin, cardiovascular system, head, eyes, ears, nose, and throat, central nervous system, respiratory system, neck, peripheral nervous system, abdomen/liver/spleen, musculoskeletal system.
Measured: Post-randomization to End of Trial Visit (42 [± 3] days)
Number of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results
Measured: From first dose of study drug to End of Trial Visit (42 [± 3] days)
Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR)
Measured: Study Baseline, Day 15/Discharge, Day 42/End of Trial

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Feb 20173 Aug 2017

First posted27 Mar 2017
Study start28 Feb 2017
Primary completion3 Aug 2017
Study completion3 Aug 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03091920
Sponsor's protocol ID: C1973-202
Status last verified: Aug 2020
First submitted: 8 Mar 2017
Last updated: 31 Aug 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Publications

Tawa M, Nakagawa K, Ohkita M. Soluble guanylate cyclase stimulators and activators as potential antihypertensive drugs. Hypertens Res. 2025 Apr;48(4):1458-1470. doi: 10.1038/s41440-025-02110-5. Epub 2025 Jan 20.
PubMed 39833553
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.
PubMed 31858186

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 31 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03091920
Acronym / sponsor ID: C1973-202
Conditions: Diabetes Mellitus, Type 2, Hypertension
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: Cyclerion TherapeuticsIndustry (pharma, biotech, devices)
Study start: 28 Feb 2017 (actual)
Primary completion: 3 Aug 2017 (actual)
Study completion: 3 Aug 2017 (actual)
First posted: 27 Mar 2017 (actual)
Results: Posted 31 Aug 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 3

Arm	Type	Receives
IW-1973 QD/QD	Experimental	Drug: IW-1973, Drug: PlaceboOn Days 1-14: IW-1973 40 mg taken once daily (QD) in morning (AM) and placebo taken QD at night (PM).
IW-1973 BID (Twice Daily)/QD	Experimental	Drug: IW-1973, Drug: PlaceboOn Days 1-7: IW-1973 20 mg taken in AM and IW-1973 20 mg taken in PM. On Days 8-14: IW-1973 40 mg taken QD in AM and placebo taken QD in PM.
Placebo	Placebo comparator	Drug: PlaceboOn Days 1-14: Placebo taken in AM and in PM.

Who may qualify

Ages: 30 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IW-1973Oral Tablet	Drug	IW-1973 BID (Twice Daily)/QD, IW-1973 QD/QD
PlaceboOral Tablet	Drug	IW-1973 BID (Twice Daily)/QD, IW-1973 QD/QD, Placebo

Primary outcome

Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Time frame: 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
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Time frame: 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
Change From Study Baseline Over Time in Supine Pulse
Time frame: 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
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Time frame: Baseline, Days 1-14, Day 15, 21, 42
Orthostatic Systolic Blood Pressure Over Time
Time frame: 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
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Orthostatic Diastolic Blood Pressure Over Time
Time frame: 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
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Orthostatic Pulse Over Time
Time frame: 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
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Time frame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Time frame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Time frame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Time frame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13
Time frame: Baseline, Day 13 predose AM
RHI is a measure of the extent of vessel dilatation and augmentation in vascular blood flow after a prespecified period of flow interruption. RHI is determined as the ratio of the post-to-pre- occlusion peripheral arterial tonometry amplitude of the tested (occluded) arm, divided by the post to-pre-occlusion ratio of the control arm. RHI values >1.67 indicate normal endothelial function, while values ≤1.67 indicate endothelial dysfunction.
Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay
Time frame: Baseline, Day 8, Day 14
Platelet reactivity, as measured by VerifyNow PRU assay, and presented as number of participants with < 180 PRU or ≥ 180 PRU post-baseline (Days 8 and 14), by baseline category. The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values < 180 units indicate impairment of platelet aggregation.
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
Time frame: Baseline, Day 8, Day 14
Platelet reactivity, as measured by VerifyNow ARU assay, and presented as number of participants with ≤ 549 ARU or > 549 ARU post-baseline (Days 8 and 14), by baseline category. Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the glycoprotein (GP)IIb/IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU.
Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay
Time frame: Study Baseline (Day 1 predose), Day 8 (predose AM), Day 14 (predose AM)
The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values <180 PRU indicate impairment of platelet aggregation.
Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay
Time frame: Study Baseline (Day 1 predose), Day 8 (pre AM dose), Day 14 (pre AM dose)
Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the GPIIb IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU.
Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin
Time frame: Study baseline (defined as the last non-missing assessment before the first administration of study drug), Day 8, pre-AM dose, Day 15
Blood samples were taken for fasting glucose and insulin levels. From these results, insulin resistance was then estimated using the updated homeostasis model assessment method for insulin resistance (HOMA-IR) computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Typically a cutoff of HOMA-IR for identifying those with insulin resistance is 2.5.
IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7
Time frame: Days 1 and 7 (AM): 1, 3, and 6 hours postdose
Equivalent to AUC from time 0 to the last measurable concentration (AUClast), with time of last measurable concentration (Tlast)=12 hours for BID dosing and Tlast=24 hours for QD dosing.
IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7
Time frame: Days 1 and 7 (AM): 1, 3, and 6 hours postdose
IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7
Time frame: Days 1 and 7 (AM): 1, 3, and 6 hours postdose
IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7
Time frame: Days 1 and 7: predose; Day 2 (BID AM): predose; Day 6 (BID PM/QD): predose
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
Time frame: Day 8 and 14: 1, 3, 6h (± 5 min) postdose
IW-1973 Pharmacokinetics: AUCtau on Day 14
Time frame: Day 14: 1, 3, 6h (± 5 min) postdose
IW-1973 Pharmacokinetics: Tmax on Days 8 and 14
Time frame: Day 8 and 14: 1, 3, 6h (± 5 min) postdose
IW-1973 Pharmacokinetics: Cmax on Days 8 and 14
Time frame: Day 8 and 14: 1, 3, 6h (± 5 min) postdose
IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14
Time frame: Days 13 and 14: predose
IW-1973 Pharmacokinetics: Apparent Total Body Clearance (CL/F) on Day 14
Time frame: Day 14: 1, 3, 6h (± 5 min) postdose
IW-1973 Pharmacokinetics: Apparent Volume of Distribution During the Terminal Phase (Vz/F) on Day 14
Time frame: Day 14: 1, 3, 6h (± 5 min) postdose
IW-1973 Pharmacokinetics: Apparent Terminal Elimination Phase Half-Life (t1/2)
Time frame: 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)
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
Time frame: From first dose of study drug to End of Trial Visit (42 [± 3] days)
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. AEs of clinical interest (AECI) included those related to bleeding and to hypotension. Study drug causality as assessed by the Investigator who was blinded to study drug assignment.
Number of Participants With Clinically Meaningful Postbaseline Laboratory Test Results
Time frame: From first dose of study drug to End of Trial Visit (42 [± 3] days)
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
Time frame: From first dose of study drug to End of Trial Visit (42 [± 3] days)
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 heart rate (SHR): ≥ 110 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 heart rate (StHR): ≥ 110 bpm and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm. Orthostatic systolic blood pressure (SBP): ↓ > 20 mmHg from supine to standing. Orthostatic diastolic blood pressure (DBP): ↓ > 15 mmHg from supine to standing. Orthostatic HR: ↓ > 30 bpm from supine to standing.
Number of Participants With Clinically Significant Post-Randomization Physical Examination Findings
Time frame: Post-randomization to End of Trial Visit (42 [± 3] days)
Physical examinations included examination and assessment of the following: general appearance, lymph nodes, skin, cardiovascular system, head, eyes, ears, nose, and throat, central nervous system, respiratory system, neck, peripheral nervous system, abdomen/liver/spleen, musculoskeletal system.
Number of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results
Time frame: From first dose of study drug to End of Trial Visit (42 [± 3] days)
Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR)
Time frame: Study Baseline, Day 15/Discharge, Day 42/End of Trial

Results and safety

Results posted to the registry on 31 Aug 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	6	6
IW-1973 40 mg Twice Dily (BID)/Once Daily (QD)	10	9
IW-1973 40 mg QD/QD	10	10

Primary outcome: Change From Study Baseline Over Time in Supine Systolic Blood Pressure

Time frame: 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. Least squares mean (Standard Error). Unit: mmHg

Measure	Placebo n = 6	IW-1973 40 mg BID/QD n = 10	IW-1973 40 mg QD/QD n = 10
Study Baseline (Day 1 predose AM)	130.2 (11.1)	120.1 (8.9)	128.6 (10.1)
Day 1 postdose AM: 1 hour	-6.8 (4.8)	-7.7 (3.9)	-6.2 (3.7)
Day 1 postdose AM: 4 hour	4.4 (6.0)	-9.5 (4.9)	-11.1 (4.6)
Day 1 postdose AM: 8 hour	0.5 (5.0)	-9.4 (4.0)	-2.7 (3.8)
Day 1 predose PM	1.8 (6.3)	-6.9 (5.1)	-1.7 (4.8)
Day 1 postdose PM: 1 hour	-0.6 (5.6)	-3.9 (4.5)	-5.0 (4.3)
Day 2 predose AM	5.5 (3.5)	-2.9 (2.8)	-0.2 (2.7)
Day 2 postdose AM: 1 hour	2.0 (4.6)	-13.4 (3.7)	-7.4 (3.5)

Placebo vs IW-1973 40 mg BID/QD: LS Mean Difference: -0.9 (95% CI -14.2 to 12.4)
Placebo vs IW-1973 40 mg QD/QD: Least squares mean difference: 0.6 (95% CI -11.8 to 12.9)
Placebo vs IW-1973 40 mg BID/QD: Least squares mean difference: -13.9 (95% CI -30.6 to 2.8)

Population analysed: Pharmacodynamic (PD) Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.

Primary outcome: Change From Study Baseline Over Time in Supine Diastolic Blood Pressure

Measure	Placebo n = 6	IW-1973 40 mg BID/QD n = 10	IW-1973 40 mg QD/QD n = 10
Study Baseline (Day 1 predose AM)	80.3 (6.9)	75.5 (4.4)	74.8 (5.9)
Day 1 postdose AM: 1 hour	-3.1 (2.4)	-5.7 (1.8)	-5.1 (1.8)
Day 1 postdose AM: 4 hour	-0.3 (2.4)	-3.2 (1.8)	-7.4 (1.8)
Day 1 postdose AM: 8 hour	0.9 (2.3)	-4.6 (1.7)	-3.7 (1.7)
Day 1 predose PM	-1.3 (2.2)	-4.9 (1.6)	-3.5 (1.6)
Day 1 postdose PM: 1 hour	-0.9 (3.4)	-5.9 (2.5)	-3.7 (2.5)
Day 2 predose AM	3.1 (2.0)	-1.3 (1.5)	0 (1.5)
Day 2 postdose AM: 1 hour	-1.4 (2.4)	-8.1 (1.8)	-6.7 (1.8)

Placebo vs IW-1973 40 mg BID/QD: Least squares mean difference: -2.6 (95% CI -8.9 to 3.8)
Placebo vs IW-1973 40 mg QD/QD: Least squares mean difference: -2.0 (95% CI -8.4 to 4.5)
Placebo vs IW-1973 40 mg BID/QD: Least squares mean difference: -2.9 (95% CI -9.2 to 3.4)

Population analysed: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.

Primary outcome: Change From Study Baseline Over Time in Supine Pulse

Measure	Placebo n = 6	IW-1973 40 mg BID/QD n = 10	IW-1973 40 mg QD/QD n = 10
Study Baseline (Day 1 predose AM)	70.3 (13.7)	70.3 (10.9)	70.0 (10.3)
Day 1 postdose AM: 1 hour	1.0 (4.1)	7.2 (3.1)	10.2 (3.1)
Day 1 postdose AM: 4 hour	4.3 (3.4)	4.3 (2.7)	8.8 (2.7)
Day 1 postdose AM: 8 hour	2.8 (2.8)	2.6 (2.2)	4.5 (2.2)
Day 1 predose PM	0 (2.7)	5.1 (2.1)	5.3 (2.1)
Day 1 postdose PM: 1 hour	2.3 (2.8)	4.6 (2.2)	3.7 (2.2)
Day 2 predose AM	-2.6 (2.3)	-1.7 (1.8)	-1.9 (1.8)
Day 2 postdose AM: 1 hour	7.0 (4.1)	9.5 (3.1)	11.3 (3.1)

Placebo vs IW-1973 40 mg BID/QD: Least squares mean difference: 6.2 (95% CI -4.4 to 16.8)
Placebo vs IW-1973 40 mg QD/QD: Least squares mean difference: 9.1 (95% CI -1.5 to 19.8)
Placebo vs IW-1973 40 mg BID/QD: Least squares mean difference: 0 (95% CI -9.0 to 9.0)

Population analysed: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.

Primary outcome: Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time

Time frame: Baseline, Days 1-14, Day 15, 21, 42. Number. Unit: percentage of participants

Measure	Placebo n = 6	IW-1973 40 mg BID/QD n = 10	IW-1973 40 mg QD/QD n = 10
Baseline	33.3	80.0	60.0
Day 1	100	100	100
Day 2	66.7	100	100
Day 3	66.7	100	90.0
Day 4	50.0	100	90.0
Day 5	50.0	70.0	90.0
Day 6	66.7	90.0	90.0
Day 7	50.0	90.0	90.0

Population analysed: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.

Adverse events

Time frame: From first dose of study drug to End of Trial Visit (42 [± 3] days). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
IW-1973 40 mg BID/QD	1 of 10 (10%)	6 of 10 (60%)	0 of 10
IW-1973 40 mg QD/QD	0 of 10 (0%)	8 of 10 (80%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39833553Tawa M, Nakagawa K, Ohkita M. Soluble guanylate cyclase stimulators and activators as potential antihypertensive drugs. Hypertens Res. 2025 Apr;48(4):1458-1470. doi: 10.1038/s41440-025-02110-5. Epub 2025 Jan 20.
Derived from this study: PubMed 31858186Hanrahan 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.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IW-1973 in people with Diabetes Mellitus, Type 2 and Hypertension, run by Cyclerion Therapeutics at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Study Baseline Over Time in Supine Systolic Blood Pressure (time frame: 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). The study lists 47 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03091920, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2020.