Type 2 Diabetes Mellitus With Diabetic NephropathyPhase 2NCT03217591
A Study to Evaluate the Soluble Guanylate Cyclase (sGC) Stimulator IW-1973 in Diabetic Nephropathy / Diabetic Kidney Disease as Measured by Albuminuria
A Phase 2 study testing IW-1973 in people with Type 2 Diabetes Mellitus With Diabetic Nephropathy, run by Akebia Therapeutics at 54 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 25 to 75 years
- Conditions the study is for
- Type 2 Diabetes Mellitus With Diabetic Nephropathy
- 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
- 156 participants
- Where
- 54 sitesUnited States
- Study dates
- 1 Aug 2017to 20 Aug 2019
- 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 25 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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.
- Other inclusion criteria per protocol.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
- Other exclusion criteria per protocol.
Trial locations and contacts
54 sites in 1 country.
54 sites in 1 country
United States54 sites
Albany Medical College, Division of Community Endocrinology
Albany, New York, 12206
Atlanta Center for Clinical Research Nephrology
Atlanta, Georgia, 30342
Pioneer Research Solutions
Beaumont, Texas, 77702
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Joslin Diabetes Center
Boston, Massachusetts, 02215
Burke Internal Medicine and Research
Burke, Virginia, 22015
Research by Design, LLC
Chicago, Illinois, 60643
California Institute of Renal Research
Chula Vista, California, 91910
Columbus Regional Research Institute
Columbus, Georgia, 31904
Creekside Endocrine Associates
Denver, Colorado, 80209
Academy of Diabetes, Thyroid and Endocrine, P.A.
El Paso, Texas, 79935
Aa Mrc, Llc
Flint, Michigan, 48504
The Medical Group of Texas
Fort Worth, Texas, 76116
Rockwood Medical Center
Fort Worth, Texas, 76164
American Health Network of Indiana
Franklin, Indiana, 46131
St. Joseph Heritage Healthcare (St. Jude Hospital DBA)
Fullerton, California, 92835
Physicians East Endocrinology
Greenville, North Carolina, 27834
Mountain View Clinical Research
Greer, South Carolina, 29651
AGA Clinical Trials
Hialeah, Florida, 33012
Endocrine IPS, PLLC
Houston, Texas, 77079
Pioneer Research Solutions, Inc.
Houston, Texas, 77099
California Institute of Renal Research
La Mesa, California, 91942
FMC Science, LLC
Lampasas, Texas, 76550
Gwinnett Biomedical Research
Lawrenceville, Georgia, 30046
Kentucky Diabetes Endocrinology Center
Lexington, Kentucky, 40503
NJ Heart, P.A.
Linden, New Jersey, 07036
Torrance Clinical Research Institute, Inc.
Lomita, California, 90717
American Institute of Research
Los Angeles, California, 90017
Academic Medical Research Institute
Los Angeles, California, 90022
East Coast Institute for Clinical Research
Macon, Georgia, 31210
East Coast Institute for Research
Macon, Georgia, 31210
Manassas Clinical Research Center
Manassas, Virginia, 20110
My Kidney Center
Manhattan, Kansas, 66502
University of Tennessee Health Science Center at Memphis University Hospital
Memphis, Tennessee, 38104
Leon Medical Research Corp.
Miami, Florida, 33015
Elite Clinical Research
Miami, Florida, 33144
DL Research Solutions
Miami, Florida, 33155
Premier Research Associates, Inc.
Miami, Florida, 33165
Sweet Hope Research Speciality, Inc.
Miami Lakes, Florida, 33016
Saltzer Medical Group
Nampa, Idaho, 83686
Christiana Care Health Services
Newark, Delaware, 19713
California Medical Research Associates, Inc. (CMRA)
Northridge, California, 91324
South Carolina Nephrology & Hypertension Center
Orangeburg, South Carolina, 29118
IMIC, Inc.
Palmetto Bay, Florida, 33157
Riverside Nephrology Physicians, Inc.
Riverside, California, 92503
Clinical Advancement Center PLLC
San Antonio, Texas, 78215
Briggs Clinical Research
San Antonio, Texas, 78224
California Kidney Specialists
San Dimas, California, 91773
North American Research Institute
San Dimas, California, 91773
UCLA
Santa Monica, California, 90025
Northside Endocrinology
Spokane, Washington, 99208
St. Louis Heart & Vascular, P.C.
St Louis, Missouri, 63136
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Torrance, California, 90502
The George Washington University Medical Faculty Associates
Washington D.C., District of Columbia, 20037
About this study
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
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.
- Being tested
- IW-1973, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IW-1973Drug
Oral Tablet
IW-1973Drug
Oral Tablet
PlaceboDrug
Oral Tablet
| Study group | Role | What they receive |
|---|---|---|
| IW-1973 Low Dose | Experimental | Administered daily for 12 weeks Receives: Drug: IW-1973 |
| IW-1973 High Dose | Experimental | Administered daily for 12 weeks Receives: Drug: IW-1973 |
| Placebo | Placebo comparator | Placebo to match experimental drug administered daily for 12 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline; Week 8 to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2017
- Study start1 Aug 2017
- Primary completion20 Aug 2019
- Study completion20 Aug 2019
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 (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes Mellitus With Diabetic NephropathyStudies 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
- Model description
- Phase 2, randomized, double-blind, placebo-controlled, parallel-group study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 156 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akebia Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cyclerion Therapeutics
- Responsible party
- Sponsor
- Investigators
- John Hanrahan, MD MPH, Study director, Cyclerion Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03217591
- Sponsor's protocol ID
- C1973-203
- Status last verified
- Aug 2022
- First submitted
- 12 Jul 2017
- Last updated
- 15 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33328269
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03217591
- Acronym / sponsor ID
- C1973-203
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 156 participants (actual)
- Lead sponsor
- Akebia TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Cyclerion Therapeutics
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 20 Aug 2019 (actual)
- Study completion
- 20 Aug 2019 (actual)
- First posted
- 14 Jul 2017 (actual)
- Results
- Posted 15 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- Phase 2, randomized, double-blind, placebo-controlled, parallel-group study
| Arm | Type | Receives |
|---|---|---|
| IW-1973 Low Dose | Experimental | Drug: IW-1973Administered daily for 12 weeks |
| IW-1973 High Dose | Experimental | Drug: IW-1973Administered daily for 12 weeks |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo to match experimental drug administered daily for 12 weeks |
Who may qualify
- Ages
- 25 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- 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.
Key exclusion criteria (15 listed)
- 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.
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 Low Dose |
| IW-1973Oral Tablet | Drug | IW-1973 High Dose |
| PlaceboOral Tablet | Drug | Placebo |
Primary outcome
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Study Drug-Related TEAEs
Time frame: Day 1 up to Day 115
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.
Percent Change From Baseline in Urine Albumin Creatinine Ratio (UACR) Over Weeks 8 and 12
Time frame: Baseline; Week 8 to Week 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33328269Hanrahan 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.
- Individual participant dataSharing planned: No
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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.
John Hanrahan, MD MPH study director
Cyclerion Therapeutics, Inc.
54 sites 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 Type 2 Diabetes Mellitus With Diabetic Nephropathy, run by Akebia Therapeutics at 54 sites 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 12 inclusion and 15 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 15 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 54 sites 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 15 Sep 2022). 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?
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Study Drug-Related TEAEs (time frame: Day 1 up to Day 115). The study lists 2 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 NCT03217591, which also lists 1 linked publication.
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 15 Sep 2022; AzTrials last refreshed its copy on 26 Oct 2026.