Safety and Efficacy of Oral GKT137831 in Patient With Type 2 Diabetes and Albuminuria

A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study Evaluating the Safety and Efficacy of Oral GKT137831 in Patients With Type 2 Diabetes and Albuminuria

NADPH oxidase enzymes (NOX) have been implicated in the development of several diabetic complications including diabetic nephropathy. GKT137831 is the first in class NOX1/4 inhibitor.

The primary objective of this study is to evaluate the efficacy of oral GKT137831 in patients with residual albuminuria despite maximal inhibition of the renin angiotensin aldosterone system.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus With Diabetic Nephropathy
• Intervention / Treatment: Drug: GKT137831; Drug: Placebo

Detailed Description

A double-blind, placebo-controlled, randomized, multicenter, parallel group Phase 2 study assessing a 12-week period of treatment with oral GKT137831 administered in addition to standard of care for patients with type 2 diabetes.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • Deakin University school of medicine
    • Heidelberg, Victoria, Australia, 3081
      • Austin Health
    • Melbourne, Victoria, Australia, 3004
      • Baker Institute
    • Ringwood East, Victoria, Australia, 3135
      • Maroondah ECRU
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Captain Stirling Medical Centre
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6E1M7
      • Endocrine Research Inc.
  • Ontario
    • Brampton, Ontario, Canada, L6S 0C9
      • LMC Diabetes & Endocrinology
    • Kitchener, Ontario, Canada, N2H 5Z8
      • Clinical Research Solutions
    • Thornhill, Ontario, Canada, L4J8L7
      • LMC Diabetes and Endocrinology
    • Toronto, Ontario, Canada, M4C 5T2
      • Toronto East General Medical Centre
  • Quebec
    • Montreal, Quebec, Canada, H1Y 3L1
      • Medpharmgene
• Czechia
  • Huzova, Czechia, 2624
    • Nemocnice Havlíčkův Brod
  • Novy Bydzov, Czechia
    • Oblastni nemocnice Jicin a.s.
  • Olomouc, Czechia
    • Faculty Hospital and Palacky University Olomouc
  • Prague, Czechia, 14900
    • Milan Kvapil s.r.o. diabetology ambulance
  • Praha, Czechia, 4021
    • IKEM
• Germany
  • Aschaffenburg, Germany, 63739
    • Studienzentrum Haematologie/Onkologie/Diabeteologie
  • Elsterwerda, Germany, 4906
    • ZKS Suedbrandenburg GmbH
  • Mainz, Germany, 55116
    • IKFE - Institute for Clinical Research and Development
  • Munchen, Germany, 48155
    • IDFM
• Poland
  • Gdansk, Poland, 80-546
    • Centrum Badaa Klinicznych PI-House Sp. z o.o.
  • Krakow, Poland, 30-015
    • LANDA Specjalistyczne Gabinety Lekarskie
  • Opole, Poland, 45367
    • Medicus w Opolu sp z o.o.
  • Poznan, Poland, 61-655
    • Praktyka Lekarska Ewa Krzyzagorska
  • Staszow, Poland, 28200
    • KO-MED Centra Kliniczne Sp. z o.o.
  • Szczecin, Poland, 70-711
    • Department of Nephrology, Transplantationa and Internal Medicine
  • Warsaw, Poland, 01-868
    • Medica Pro Familia Sp. z o.o. S.K.A.
• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Advanced Arizona Clinical Research
  • California
    • Orange, California, United States, 92868
      • The Endocrine Medical Group, Inc
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • Hollywood, Florida, United States, 33021
      • The Center for Diabetes and Endocrine Care
    • Jacksonville, Florida, United States, 33216
      • Jacksonville Center for Clinical Research
    • Miami, Florida, United States, 33165
      • Genoma Research Group, Inc.
    • Miami, Florida, United States, 33175
      • Coral Research Clinic
    • Pembroke Pines, Florida, United States, 33028
      • Pines Clinical Research Inc.
    • Port Charlotte, Florida, United States, 33952
      • Volunteer Medical Research
  • Illinois
    • Chicago, Illinois, United States, 60612
      • John H. Stroger Jr. Hospital of Cook County
  • Indiana
    • Indianapolis, Indiana, United States, 46234
      • Community Medical Research Partners
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Kansas City VA Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Creighton Diabetes Center
  • Ohio
    • Dayton, Ohio, United States, 45424
      • LLC DBA AccessMD Clinical Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37408
      • Southeast Renal Research Institute
  • Texas
    • Dallas, Texas, United States, 75201
      • The University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77090
      • 17070 Red Oak dr Ste 103
    • San Antonio, Texas, United States, 78229
      • Dialysis West University Health System
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire VA Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53095
      • Zablocki VAMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male or female aged 18 to 80 years
• History of type 2 diabetes, defined as fasting plasma glucose ≥7.0 mmol/L (126 mg/dL) or a glycated hemoglobin (HbA1c) >6.5% (48 mmol/mol) on at least 2 occasions prior to screening.
• Albuminuria defined as a UACR of 300 to 3500 mg/g.
• An eGFR ≥30 mL/min/1.73 m2, as calculated by the CKD-EPI formula.
• Must be taking an ACEI or an ARB for at least 6 weeks prior to the first screening visit (Visit 1) and during the screening period. The dose must have been stable for at least 4 weeks prior to the first screening visit (Visit 1). Combination therapy associating an ACEI and an ARB is not permitted.

Key Exclusion Criteria:

• History of type 1 diabetes
• Any other non-diabetic kidney disease(s) except for hypertensive nephropathy which is acceptable.
• Diagnostic or interventional procedure requiring a contrast agent within 4 weeks of the first screening visit (Visit 1) or planned during the study.
• History of renal transplant or planned renal transplant during the study.
• A history of acute renal dialysis or acute kidney injury (defined according to the Kidney Disease: Improving Global Outcomes [KDIGO] definition) within 12 weeks of the first screening visit (Visit 1)
• HbA1c level >11% (97 mmol/mol).
• History of hypothyroidism requiring hormone replacement therapy.
• History of active cardiovascular disease
• A personal or family history of long QT syndrome.
• Administration of any investigational product within 30 days or within 5 half-lives of the investigational agent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GKT137831; GKT137831 100 mg capsules twice a day	Drug: GKT137831; 1 capsule of 100 mg twice a day for the first 6 weeks of treatment, and 2 capsules of 100 mg twice a day for next 6 weeks of treatment
Placebo Comparator: Placebo; Placebo capsule twice a day	Drug: Placebo; 1 capsule of Placebo, twice a day, oral treatment self-administered by the patient for the 12 weeks of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Albuminuria Absolute Value and Ratio to Baseline by Study Visit and Treatment Group	UACR from baseline to Visits 9, 10, and 11 (i.e. weeks 8, 10 and 12 of the treatment period, respectively). Baseline for UACR is defined as the geometric mean of the geometric means of the UACR values measured on Day-14 (visit 4) and Day 1 (visit 5). End of treatment is defined as the geometric mean of the geometric means of the UACR values measured at week 8 (visit 9), week 10 (visit 10) and week 12 (visit 11).	Visit 4 (week -2) to visit 11 (week 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose Metabolism by Homeostatic Model Assessment (HOMA)	Change in homeostasis model assessment-estimated β cell function (HOMA-B) and homeostasis model assessment-estimated insulin resistance (HOMA-IR) from baseline. HOMA-IR = fasting insulin (μIU/mL) x fasting glucose (mM/L)/22.5. A higher HOMA-IR value indicates greater insulin resistance. HOMA-B = 20 x fasting insulin (μIU/mL)/(fasting glucose [mmol/mL] - 3.5). Generally, a higher HOMA-B value indicates better beta-cell function, meaning the pancreas is producing insulin effectively.	Visits 5 (week 0), 8 (week 6), and 11 (week 12)
Glucose Metabolism HbA1c	Change in HbA1c from Baseline	Visit 5 (week 0), 8 (week 6) and 11 (week 12)
24 Hours Albumin Excretion	Change in 24 hours Albumin excretion from baseline	Visits 5 (week 0) and 11 (week 12)
24 Hours Urine UACR	Change in 24 hours Urine UACR from baseline	Visits 5 (week 0) and 11 (week 12)
eGFR Change by Study Visit	Change in eGFR from baseline by study visit	Visits 5 (week 0), 6 (week 2), 7 (week 4), 8 (week 6), 9 (week 8), 10 (week 10), 11 (week 12), follow up (week 16)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Erectile Dysfunction	Changes at week 12 in IEFF questionnaire assessing erectile dysfunction in patients presenting with these diabetic complications at baseline (Baseline <=25 in the erectile function domain)- Score from 1 to 30. Score 1 to 10: severe erectile dysfunction, Score 11-16: moderate erectile dysfunction, Score 17-25: light erectile dysfunction, Score 26-30: normal erectile function	Visits 5 (week 0), and 11 (week 12)
Neuropathic Pain	Changes in Visual Analog Scale (VAS) assessing neuropathic leg pain in patients presenting with these diabetic complications at baseline (subjects with a baseline VAS>=20mm are included). A 100mm VAS scale was used with a range from 0-100mm where a higher score means worse pain. The presence of neuropathic pain is defined a VAS score of at least 20 mm.	Visits 5 (week 0), and 11 (week 12)

Collaborators and Investigators

• Sponsor: Calliditas Therapeutics AB
• Investigators: Study Director: Philippe Wiesel, MD, Calliditas Therapeutics AB

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: June 18, 2013
• First Submitted That Met QC Criteria: December 9, 2013
• First Posted (Estimated): December 12, 2013

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 7, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Type 2 diabetes; Proteinuria; Albuminuria
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Urination Disorders; Urological Manifestations; Glucose Metabolism Disorders; Diabetes Complications; Proteinuria; Diabetes Mellitus, Type 2; Diabetes Mellitus; Diabetic Nephropathies; Albuminuria
• Other Study ID Numbers: GSN000200