A Study to Evaluate the Soluble Guanylate Cyclase (sGC) Stimulator IW-1973 in Diabetic Nephropathy / Diabetic Kidney Disease as Measured by Albuminuria

NCT03217591 | Completed Phase 2 Results FDA Drug

• 1 other identifier: C1973-203
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 54

Brief 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.

Conditions

Type 2 Diabetes Mellitus With Diabetic Nephropathy

Outcome Measures

Primary Outcomes (2)

• Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Study Drug-Related TEAEs

  An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration. Causality relationship to study drug was per Investigator assessment.

  Day 1 up to Day 115

• Percent Change From Baseline in Urine Albumin Creatinine Ratio (UACR) Over Weeks 8 and 12

  Urine samples were collected for the analysis of UACR. UACR (milligrams per gram \[mg/g\]) was calculated as urine albumin (mg per deciliter \[mg/dL\]) / urine creatinine (g/dL). Change from Baseline was calculated as the average of the UCAR values at Weeks 8 and 12 minus the Baseline value. Data were analyzed using a mixed-effects model repeated measures (MMRM) analysis with change from Baseline in log-transformed UACR as the response variable, treatment, visit, treatment-by visit interaction, and Baseline estimated glomerular filtration rate stratum as fixed effects, Baseline log-transformed UACR and Baseline mean arterial pressure as covariates, and unstructured as the variance-covariance structure.

  Baseline; Week 8 to Week 12

Study Arms (3)

IW-1973 Low Dose

EXPERIMENTAL

Administered daily for 12 weeks

Drug: IW-1973

IW-1973 High Dose

EXPERIMENTAL

Administered daily for 12 weeks

Drug: IW-1973

Placebo

PLACEBO COMPARATOR

Placebo to match experimental drug administered daily for 12 weeks

Drug: Placebo

Interventions

IW-1973 DRUG

Oral Tablet

IW-1973 Low Dose

Placebo DRUG

Oral Tablet

Placebo

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• Urine albumin-to-creatinine ratio (UACR) \>200 mg/g at the Screening and Baseline Visits and \<5000 mg/g at Screening and Baseline Visits
• Serum albumin \>3.0 g/dL at the Screening and Baseline Visits
• Hemoglobin A1c (HbA1c) ≤11% at the Screening and Baseline Visits
• 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.

You may not qualify if:

• 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:
• Hospitalization for myocardial infarction (MI), unstable angina, or heart failure
• New-onset angina with positive functional study or coronary angiogram revealing stenosis
• 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.

Sponsors & Collaborators

• Akebia Therapeutics: lead
• Cyclerion Therapeutics: collaborator

Study Sites (54)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

California Institute of Renal Research

Chula Vista, California, 91910, United States

Location

St. Joseph Heritage Healthcare (St. Jude Hospital DBA)

Fullerton, California, 92835, United States

Location

California Institute of Renal Research

La Mesa, California, 91942, United States

Location

Torrance Clinical Research Institute, Inc.

Lomita, California, 90717, United States

Location

American Institute of Research

Los Angeles, California, 90017, United States

Location

Academic Medical Research Institute

Los Angeles, California, 90022, United States

Location

California Medical Research Associates, Inc. (CMRA)

Northridge, California, 91324, United States

Location

Riverside Nephrology Physicians, Inc.

Riverside, California, 92503, United States

Location

California Kidney Specialists

San Dimas, California, 91773, United States

Location

North American Research Institute

San Dimas, California, 91773, United States

Location

UCLA

Santa Monica, California, 90025, United States

Location

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Creekside Endocrine Associates

Denver, Colorado, 80209, United States

Location

Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

The George Washington University Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

AGA Clinical Trials

Hialeah, Florida, 33012, United States

Location

Leon Medical Research Corp.

Miami, Florida, 33015, United States

Location

Elite Clinical Research

Miami, Florida, 33144, United States

Location

DL Research Solutions

Miami, Florida, 33155, United States

Location

Premier Research Associates, Inc.

Miami, Florida, 33165, United States

Location

Sweet Hope Research Speciality, Inc.

Miami Lakes, Florida, 33016, United States

Location

IMIC, Inc.

Palmetto Bay, Florida, 33157, United States

Location

Atlanta Center for Clinical Research Nephrology

Atlanta, Georgia, 30342, United States

Location

Columbus Regional Research Institute

Columbus, Georgia, 31904, United States

Location

Gwinnett Biomedical Research

Lawrenceville, Georgia, 30046, United States

Location

East Coast Institute for Clinical Research

Macon, Georgia, 31210, United States

Location

East Coast Institute for Research

Macon, Georgia, 31210, United States

Location

Saltzer Medical Group

Nampa, Idaho, 83686, United States

Location

Research by Design, LLC

Chicago, Illinois, 60643, United States

Location

American Health Network of Indiana

Franklin, Indiana, 46131, United States

Location

My Kidney Center

Manhattan, Kansas, 66502, United States

Location

Kentucky Diabetes Endocrinology Center

Lexington, Kentucky, 40503, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Aa Mrc, Llc

Flint, Michigan, 48504, United States

Location

St. Louis Heart & Vascular, P.C.

St Louis, Missouri, 63136, United States

Location

NJ Heart, P.A.

Linden, New Jersey, 07036, United States

Location

Albany Medical College, Division of Community Endocrinology

Albany, New York, 12206, United States

Location

Physicians East Endocrinology

Greenville, North Carolina, 27834, United States

Location

Mountain View Clinical Research

Greer, South Carolina, 29651, United States

Location

South Carolina Nephrology & Hypertension Center

Orangeburg, South Carolina, 29118, United States

Location

University of Tennessee Health Science Center at Memphis University Hospital

Memphis, Tennessee, 38104, United States

Location

Pioneer Research Solutions

Beaumont, Texas, 77702, United States

Location

Academy of Diabetes, Thyroid and Endocrine, P.A.

El Paso, Texas, 79935, United States

Location

The Medical Group of Texas

Fort Worth, Texas, 76116, United States

Location

Rockwood Medical Center

Fort Worth, Texas, 76164, United States

Location

Endocrine IPS, PLLC

Houston, Texas, 77079, United States

Location

Pioneer Research Solutions, Inc.

Houston, Texas, 77099, United States

Location

FMC Science, LLC

Lampasas, Texas, 76550, United States

Location

Clinical Advancement Center PLLC

San Antonio, Texas, 78215, United States

Location

Briggs Clinical Research

San Antonio, Texas, 78224, United States

Location

Burke Internal Medicine and Research

Burke, Virginia, 22015, United States

Location

Manassas Clinical Research Center

Manassas, Virginia, 20110, United States

Location

Northside Endocrinology

Spokane, Washington, 99208, United States

Location

Related Publications (1)

• Hanrahan JP, de Boer IH, Bakris GL, Wilson PJ, Wakefield JD, Seferovic JP, Chickering JG, Chien YT, Carlson K, Cressman MD, Currie MG, Milne GT, Profy AT. Effects of the Soluble Guanylate Cyclase Stimulator Praliciguat in Diabetic Kidney Disease: A Randomized Placebo-Controlled Clinical Trial. Clin J Am Soc Nephrol. 2020 Dec 31;16(1):59-69. doi: 10.2215/CJN.08410520. Epub 2020 Dec 16.

  PMID: 33328269 DERIVED

MeSH Terms

Interventions

praliciguat

Results Point of Contact

• Title: Akebia Therapeutics
• Organization: Akebia Therapeutics

trials@akebia.com

6178446128

Study Officials

• John Hanrahan, MD MPH

  Cyclerion Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 2, randomized, double-blind, placebo-controlled, parallel-group study

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: July 14, 2017
• Study Start: August 1, 2017
• Primary Completion: August 20, 2019
• Study Completion: August 20, 2019
• Last Updated: September 15, 2022
• Results First Posted: September 15, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (54)