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

Type 2 Diabetes Mellitus With Diabetic Nephropathy Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of IW-1973 in Patients With Type 2 Diabetes With Albuminuria Treated With Renin-Angiotensin System Inhibitors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03217591
• Other study ID #: C1973-203
• Status: Completed
• Phase: Phase 2
• Start date: August 1, 2017
• Est. completion date: August 20, 2019

Study information

• Verified date: August 2022
• Source: Akebia Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: August 20, 2019
• Est. primary completion date: August 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Albuminuria
• Diabetes Mellitus, Type 2
• Diabetic Nephropathies
• Kidney Diseases
• Type 2 Diabetes Mellitus With Diabetic Nephropathy

Intervention

Drug:
• IW-1973
Oral Tablet
• IW-1973
Oral Tablet
• Placebo
Oral Tablet

Locations

Country	Name	City	State
United States	Albany Medical College, Division of Community Endocrinology	Albany	New York
United States	Atlanta Center for Clinical Research Nephrology	Atlanta	Georgia
United States	Pioneer Research Solutions	Beaumont	Texas
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Joslin Diabetes Center	Boston	Massachusetts
United States	Burke Internal Medicine and Research	Burke	Virginia
United States	Research by Design, LLC	Chicago	Illinois
United States	California Institute of Renal Research	Chula Vista	California
United States	Columbus Regional Research Institute	Columbus	Georgia
United States	Creekside Endocrine Associates	Denver	Colorado
United States	Academy of Diabetes, Thyroid and Endocrine, P.A.	El Paso	Texas
United States	Aa Mrc, Llc	Flint	Michigan
United States	Rockwood Medical Center	Fort Worth	Texas
United States	The Medical Group of Texas	Fort Worth	Texas
United States	American Health Network of Indiana	Franklin	Indiana
United States	St. Joseph Heritage Healthcare (St. Jude Hospital DBA)	Fullerton	California
United States	Physicians East Endocrinology	Greenville	North Carolina
United States	Mountain View Clinical Research	Greer	South Carolina
United States	AGA Clinical Trials	Hialeah	Florida
United States	Endocrine IPS, PLLC	Houston	Texas
United States	Pioneer Research Solutions, Inc.	Houston	Texas
United States	California Institute of Renal Research	La Mesa	California
United States	FMC Science, LLC	Lampasas	Texas
United States	Gwinnett Biomedical Research	Lawrenceville	Georgia
United States	Kentucky Diabetes Endocrinology Center	Lexington	Kentucky
United States	NJ Heart, P.A.	Linden	New Jersey
United States	Torrance Clinical Research Institute, Inc.	Lomita	California
United States	Academic Medical Research Institute	Los Angeles	California
United States	American Institute of Research	Los Angeles	California
United States	East Coast Institute for Clinical Research	Macon	Georgia
United States	East Coast Institute for Research	Macon	Georgia
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	My Kidney Center	Manhattan	Kansas
United States	University of Tennessee Health Science Center at Memphis University Hospital	Memphis	Tennessee
United States	DL Research Solutions	Miami	Florida
United States	Elite Clinical Research	Miami	Florida
United States	Leon Medical Research Corp.	Miami	Florida
United States	Premier Research Associates, Inc.	Miami	Florida
United States	Sweet Hope Research Speciality, Inc.	Miami Lakes	Florida
United States	Saltzer Medical Group	Nampa	Idaho
United States	Christiana Care Health Services	Newark	Delaware
United States	California Medical Research Associates, Inc. (CMRA)	Northridge	California
United States	South Carolina Nephrology & Hypertension Center	Orangeburg	South Carolina
United States	IMIC, Inc.	Palmetto Bay	Florida
United States	Riverside Nephrology Physicians, Inc.	Riverside	California
United States	St. Louis Heart & Vascular, P.C.	Saint Louis	Missouri
United States	Briggs Clinical Research	San Antonio	Texas
United States	Clinical Advancement Center PLLC	San Antonio	Texas
United States	California Kidney Specialists	San Dimas	California
United States	North American Research Institute	San Dimas	California
United States	UCLA	Santa Monica	California
United States	Northside Endocrinology	Spokane	Washington
United States	Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center	Torrance	California
United States	The George Washington University Medical Faculty Associates	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Akebia Therapeutics	Cyclerion Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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