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

NCT02010242 | Completed Phase 2 Results DMC

• 1 other identifier: GSN000200
• Study Type: interventional
• Target: 136
• Locations: 6 countries
• Sites: 48

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.

Conditions

Type 2 Diabetes Mellitus With Diabetic Nephropathy

Keywords

Type 2 diabetes; Proteinuria; Albuminuria

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Glucose Metabolism by Homeostatic Model Assessment (HOMA)

  Visits 5 (week 0), 8 (week 6), and 11 (week 12)

• Glucose Metabolism HbA1c

  Visit 5 (week 0), 8 (week 6) and 11 (week 12)

• 24 Hours Albumin Excretion

  Visits 5 (week 0) and 11 (week 12)

• 24 Hours Urine UACR

  Visits 5 (week 0) and 11 (week 12)

• 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)

Other Outcomes (2)

• Erectile Dysfunction

  Visits 5 (week 0), and 11 (week 12)

• Neuropathic Pain

  Visits 5 (week 0), and 11 (week 12)

Study Arms (2)

GKT137831

EXPERIMENTAL

GKT137831 100 mg capsules twice a day

Drug: GKT137831

Placebo

PLACEBO COMPARATOR

Placebo capsule twice a day

Drug: Placebo

Interventions

GKT137831 DRUG

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

GKT137831

Placebo DRUG

1 capsule of Placebo, twice a day, oral treatment self-administered by the patient for the 12 weeks of treatment.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Calliditas Therapeutics AB: lead

Study Sites (48)

Advanced Arizona Clinical Research

Tucson, Arizona, 85712, United States

Location

The Endocrine Medical Group, Inc

Orange, California, 92868, United States

Location

Clinical Research of South Florida

Coral Gables, Florida, 33134, United States

Location

The Center for Diabetes and Endocrine Care

Hollywood, Florida, 33021, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 33216, United States

Location

Genoma Research Group, Inc.

Miami, Florida, 33165, United States

Location

Coral Research Clinic

Miami, Florida, 33175, United States

Location

Pines Clinical Research Inc.

Pembroke Pines, Florida, 33028, United States

Location

Volunteer Medical Research

Port Charlotte, Florida, 33952, United States

Location

John H. Stroger Jr. Hospital of Cook County

Chicago, Illinois, 60612, United States

Location

Community Medical Research Partners

Indianapolis, Indiana, 46234, United States

Location

Kansas City VA Medical Center

Kansas City, Missouri, 64128, United States

Location

Creighton Diabetes Center

Omaha, Nebraska, 68114, United States

Location

LLC DBA AccessMD Clinical Research

Dayton, Ohio, 45424, United States

Location

Southeast Renal Research Institute

Chattanooga, Tennessee, 37408, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75201, United States

Location

17070 Red Oak dr Ste 103

Houston, Texas, 77090, United States

Location

Dialysis West University Health System

San Antonio, Texas, 78229, United States

Location

McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Zablocki VAMC

Milwaukee, Wisconsin, 53095, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Deakin University school of medicine

Geelong, Victoria, 3220, Australia

Location

Austin Health

Heidelberg, Victoria, 3081, Australia

Location

Baker Institute

Melbourne, Victoria, 3004, Australia

Location

Maroondah ECRU

Ringwood East, Victoria, 3135, Australia

Location

Captain Stirling Medical Centre

Nedlands, Western Australia, 6009, Australia

Location

Endocrine Research Inc.

Vancouver, British Columbia, V6E1M7, Canada

Location

LMC Diabetes & Endocrinology

Brampton, Ontario, L6S 0C9, Canada

Location

Clinical Research Solutions

Kitchener, Ontario, N2H 5Z8, Canada

Location

LMC Diabetes and Endocrinology

Thornhill, Ontario, L4J8L7, Canada

Location

Toronto East General Medical Centre

Toronto, Ontario, M4C 5T2, Canada

Location

Medpharmgene

Montreal, Quebec, H1Y 3L1, Canada

Location

Nemocnice Havlickuv Brod

Huzová, 2624, Czechia

Location

Oblastni nemocnice Jicin a.s.

Nový Bydžov, Czechia

Location

Faculty Hospital and Palacky University Olomouc

Olomouc, Czechia

Location

Milan Kvapil s.r.o. diabetology ambulance

Prague, 14900, Czechia

Location

IKEM

Prague, 4021, Czechia

Location

Studienzentrum Haematologie/Onkologie/Diabeteologie

Aschaffenburg, 63739, Germany

Location

ZKS Suedbrandenburg GmbH

Elsterwerda, 4906, Germany

Location

IKFE - Institute for Clinical Research and Development

Mainz, 55116, Germany

Location

IDFM

München, 48155, Germany

Location

Centrum Badaa Klinicznych PI-House Sp. z o.o.

Gdansk, 80-546, Poland

Location

LANDA Specjalistyczne Gabinety Lekarskie

Krakow, 30-015, Poland

Location

Medicus w Opolu sp z o.o.

Opole, 45367, Poland

Location

Praktyka Lekarska Ewa Krzyzagorska

Poznan, 61-655, Poland

Location

KO-MED Centra Kliniczne Sp. z o.o.

Staszów, 28200, Poland

Location

Department of Nephrology, Transplantationa and Internal Medicine

Szczecin, 70-711, Poland

Location

Medica Pro Familia Sp. z o.o. S.K.A.

Warsaw, 01-868, Poland

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Proteinuria; Albuminuria

Interventions

setanaxib

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Richard Philipson, MD Chief Medical Officer
• Organization: Calliditas Therapeutics

richard.philipson@calliditas.com

+46 556659-9766

Study Officials

• Philippe Wiesel, MD

  Calliditas Therapeutics AB

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 18, 2013
• First Posted: December 12, 2013
• Study Start: October 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: March 1, 2015
• Last Updated: February 28, 2025
• Results First Posted: February 28, 2025

Record last verified: 2025-02

Locations

US (20); DE (4); CA (6); PL (7); CZ (5); AU (6)