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

Phase 2

Completed

Conditions: Type 2 Diabetes Mellitus With Diabetic Nephropathy

Interventions: Drug: GKT137831
Drug: Placebo

Registration Number: NCT02010242

Lead Sponsor: Calliditas Therapeutics AB

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 136

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GKT137831	GKT137831	GKT137831 100 mg capsules twice a day
Placebo	Placebo	Placebo capsule twice a day

Primary Outcome Measures

Name	Time	Method
Albuminuria Absolute Value and Ratio to Baseline by Study Visit and Treatment Group	Visit 4 (week -2) to visit 11 (week 12)	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).

Secondary Outcome Measures

Name	Time	Method
Glucose Metabolism by Homeostatic Model Assessment (HOMA)	Visits 5 (week 0), 8 (week 6), and 11 (week 12)	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.
Glucose Metabolism HbA1c	Visit 5 (week 0), 8 (week 6) and 11 (week 12)	Change in HbA1c from Baseline
24 Hours Albumin Excretion	Visits 5 (week 0) and 11 (week 12)	Change in 24 hours Albumin excretion from baseline
24 Hours Urine UACR	Visits 5 (week 0) and 11 (week 12)	Change in 24 hours Urine UACR from baseline
eGFR Change 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)	Change in eGFR from baseline by study visit

Trial Locations

Locations (48): Creighton Diabetes Center
🇺🇸
Omaha, Nebraska, United States
LLC DBA AccessMD Clinical Research
🇺🇸
Dayton, Ohio, United States
Southeast Renal Research Institute
🇺🇸
Chattanooga, Tennessee, United States
The University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
17070 Red Oak dr Ste 103
🇺🇸
Houston, Texas, United States
Dialysis West University Health System
🇺🇸
San Antonio, Texas, United States
McGuire VA Medical Center
🇺🇸
Richmond, Virginia, United States
Zablocki VAMC
🇺🇸
Milwaukee, Wisconsin, United States
Pines Clinical Research Inc.
🇺🇸
Pembroke Pines, Florida, United States
Volunteer Medical Research
🇺🇸
Port Charlotte, Florida, United States
John H. Stroger Jr. Hospital of Cook County
🇺🇸
Chicago, Illinois, United States
Community Medical Research Partners
🇺🇸
Indianapolis, Indiana, United States
Kansas City VA Medical Center
🇺🇸
Kansas City, Missouri, United States
Nemocnice Havlickuv Brod
🇨🇿
Huzova, Czechia
Oblastni nemocnice Jicin a.s.
🇨🇿
Novy Bydzov, Czechia
IKFE - Institute for Clinical Research and Development
🇩🇪
Mainz, Germany
IDFM
🇩🇪
Munchen, Germany
Centrum Badaa Klinicznych PI-House Sp. z o.o.
🇵🇱
Gdansk, Poland
LANDA Specjalistyczne Gabinety Lekarskie
🇵🇱
Krakow, Poland
Medicus w Opolu sp z o.o.
🇵🇱
Opole, Poland
Praktyka Lekarska Ewa Krzyzagorska
🇵🇱
Poznan, Poland
KO-MED Centra Kliniczne Sp. z o.o.
🇵🇱
Staszow, Poland
Advanced Arizona Clinical Research
🇺🇸
Tucson, Arizona, United States
The Endocrine Medical Group, Inc
🇺🇸
Orange, California, United States
Clinical Research of South Florida
🇺🇸
Coral Gables, Florida, United States
The Center for Diabetes and Endocrine Care
🇺🇸
Hollywood, Florida, United States
Jacksonville Center for Clinical Research
🇺🇸
Jacksonville, Florida, United States
Genoma Research Group, Inc.
🇺🇸
Miami, Florida, United States
Coral Research Clinic
🇺🇸
Miami, Florida, United States
Royal Prince Alfred Hospital
🇦🇺
Camperdown, New South Wales, Australia
Deakin University school of medicine
🇦🇺
Geelong, Victoria, Australia
Austin Health
🇦🇺
Heidelberg, Victoria, Australia
Baker Institute
🇦🇺
Melbourne, Victoria, Australia
Maroondah ECRU
🇦🇺
Ringwood East, Victoria, Australia
Captain Stirling Medical Centre
🇦🇺
Nedlands, Western Australia, Australia
Endocrine Research Inc.
🇨🇦
Vancouver, British Columbia, Canada
LMC Diabetes & Endocrinology
🇨🇦
Brampton, Ontario, Canada
Clinical Research Solutions
🇨🇦
Kitchener, Ontario, Canada
LMC Diabetes and Endocrinology
🇨🇦
Thornhill, Ontario, Canada
Toronto East General Medical Centre
🇨🇦
Toronto, Ontario, Canada
Medpharmgene
🇨🇦
Montreal, Quebec, Canada
Faculty Hospital and Palacky University Olomouc
🇨🇿
Olomouc, Czechia
Milan Kvapil s.r.o. diabetology ambulance
🇨🇿
Prague, Czechia
IKEM
🇨🇿
Praha, Czechia
Studienzentrum Haematologie/Onkologie/Diabeteologie
🇩🇪
Aschaffenburg, Germany
ZKS Suedbrandenburg GmbH
🇩🇪
Elsterwerda, Germany
Department of Nephrology, Transplantationa and Internal Medicine
🇵🇱
Szczecin, Poland
Medica Pro Familia Sp. z o.o. S.K.A.
🇵🇱
Warsaw, Poland