A Study to Evaluate the Soluble Guanylate Cyclase (sGC) Stimulator IW-1973 in Diabetic Nephropathy / Diabetic Kidney Disease as Measured by Albuminuria
Condition: Type 2 Diabetes Mellitus With Diabetic Nephropathy
MeSH terms: Kidney Diseases; Diabetic Nephropathies; Albuminuria; Diabetes Mellitus, Type 2
Intervention: IW-1973; IW-1973; Placebo
Intervention description: Oral Tablet; Oral Tablet; Oral Tablet
Intervention MeSH terms: Praliciguat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Phase 2, randomized, double-blind, placebo-controlled, parallel-group study
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 156.0
Sex: All
Minimum age: 25 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      To evaluate the safety and efficacy of IW-1973 in patients with type 2 diabetes mellitus with
      albuminuria who are on a stable regimen of renin-angiotensin system inhibitors.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Patient is an ambulatory male or female from 25 to 75 years old at the Screening
             Visit.

          -  Patient has type 2 diabetes diagnosed by a physician or nurse practitioner ≥6 months
             before the Screening Visit, has been on ≥1 antihyperglycemic medication for ≥12 weeks
             preceding the Randomization Visit, and has been on a stable regimen (ie, same drug and
             same dose) of ≥1 antihyperglycemic medication for ≥28 days preceding the Randomization
             Visit. (Modification of short-acting insulin throughout the Screening Period will not
             affect eligibility.)

          -  Patient has been on a stable regimen (ie, same drug and dose) of antihypertensive
             medications, which must include an angiotensin-converting enzyme inhibitor (ACEi) or
             an angiotensin receptor blocker (ARB), for ≥28 days preceding the Randomization Visit
             and is expected to remain on their regimen through the Follow-up Visit.

          -  Patient has the following:

               1. Estimated glomerular filtration rate (eGFR) 30 to 75 mL/min/1.73 m2 by the
                  Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation
                  (1) at the Screening and Baseline Visits

               2. Urine albumin-to-creatinine ratio (UACR) >200 mg/g at the Screening and Baseline
                  Visits and <5000 mg/g at Screening and Baseline Visits

               3. Serum albumin >3.0 g/dL at the Screening and Baseline Visits

               4. Hemoglobin A1c (HbA1c) ≤11% at the Screening and Baseline Visits

               5. Systolic blood pressure (BP) of 110 to 160 mm Hg at the Screening and Baseline
                  Visits

          -  Women of childbearing potential must have a negative pregnancy test prior to
             randomization and must agree to use protocol-specified contraception from the
             Screening Visit through 60 days after the final dose of study drug.

          -  Male patients must be surgically sterile by vasectomy (conducted ≥60 days before the
             Screening Visit or confirmed via sperm analysis) or must agree to use
             protocol-specified contraception from the Screening Visit through 60 days after the
             final dose of study drug.

          -  Other inclusion criteria per protocol.

        Key Exclusion Criteria:

          -  Patient has a history of secondary hypertension (ie, renal artery stenosis, primary
             aldosteronism, or pheochromocytoma).

          -  Patient has a body mass index (BMI) <20 or >45 kg/m2 at the Screening Visit.

          -  Patient has a history of platelet dysfunction, hemophilia, von Willebrand disease,
             coagulation disorder, other bleeding diathesis, or significant, nontraumatic bleeding
             episode(s), such as from a gastrointestinal source.

          -  Patient has hepatic impairment defined as Child-Pugh A, B, C.

          -  Patient has significant comorbidities (eg, malignancy, advanced liver disease,
             pulmonary hypertension, pulmonary fibrosis, lung disease requiring supplemental
             oxygen) or other significant conditions that, in the Investigator's opinion, would
             limit the patient's ability to complete or participate in this clinical study; has
             been hospitalized for cardiovascular, renal, or metabolic cause in the 3 months before
             the Screening Visit; or has a life expectancy of less than 1 year.

          -  Patient has had prior dialysis, renal transplant, or planned renal transplant.

          -  Patient has clinically active, symptomatic, or unstable coronary artery or heart
             disease within the 3 months before the Screening Visit, defined as 1 of the following:

               1. Hospitalization for myocardial infarction (MI), unstable angina, or heart failure

               2. New-onset angina with positive functional study or coronary angiogram revealing
                  stenosis

               3. Coronary revascularization procedure

          -  Patient has a history of clinically significant hypersensitivity or allergies to any
             of the inactive ingredients contained in the active or placebo drug products.

          -  Patient has previously received IW-1973 in a study, or received an investigational
             drug during the 30 days or 5 half-lives of that investigational drug (whichever is
             longer) before the Screening Visit, or is planning to receive another investigational
             drug at any time during the study.

          -  Patient is taking specific inhibitors of phosphodiesterase 5 (PDE5), nonspecific
             inhibitors of PDE5 (including dipyridamole and theophylline), any supplements for the
             treatment of erectile dysfunction, riociguat, or nitrates or nitric oxide (NO) donors
             in any form. These medications and supplements are prohibited from 7 days before
             Randomization through the duration of the study.

          -  Patient is taking strong cytochrome P450 3A (CYP3A) inhibitors (eg, ketoconazole,
             indinavir, nelfinavir, ritonavir, saquinavir, clarithromycin, telithromycin,
             itraconazole, and nefazodone). These medications are prohibited 14 days before
             Randomization through the duration of the trial.

          -  Other exclusion criteria per protocol.