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

Type 2 Diabetes Mellitus With Diabetic Nephropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02010242
• Other study ID #: GSN000200
• Status: Completed
• Phase: Phase 2
• First received: June 18, 2013
• Last updated: March 27, 2015
• Start date: October 2013
• Est. completion date: March 2015

Study information

• Verified date: March 2015
• Source: Genkyotex Innovation SAS
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaGermany: Federal Institute for Drugs and Medical DevicesCzech Republic: State Institute for Drug ControlPoland: The Central Register of Clinical TrialsAustralia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: March 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Marrondah ECRU	East Ringwood	Victoria
Australia	Deakin University school of medicine	Geelong	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Baker Institute	Melbourne	Victoria
Australia	Captain Stirling Medical Centre	Nedlands	Western Australia
Canada	LMC Diabetes & Endocrinology	Brampton	Ontario
Canada	Clinical Research Solutions	Kitchener	Ontario
Canada	Medpharmgene	Montreal	Quebec
Canada	LMC Diabetes and Endocrinology	Thornhill	Ontario
Canada	Toronto East General Medical Centre	Toronto	Ontario
Canada	Endocrine Research Inc.	Vancouver	British Columbia
Czech Republic	Nemocnice Havlickuv Brod	Huzova
Czech Republic	Oblastni nemocnice Jicin a.s.	Novy Bydzov
Czech Republic	Faculty Hospital and Palacky University Olomouc	Olomouc
Czech Republic	Milan Kvapil s.r.o. diabetology ambulance	Prague
Czech Republic	IKEM	Praha
Germany	Studienzentrum Haematologie/Onkologie/Diabeteologie	Aschaffenburg
Germany	ZKS Suedbrandenburg GmbH	Elsterwerda
Germany	IKFE - Institute for Clinical Research and Development	Mainz
Germany	IDFM	Munchen
Poland	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	Department of Nephrology, Transplantationa and Internal Medicine	Szczecin
Poland	Medica Pro Familia Sp. z o.o. S.K.A.	Warsaw
United States	Southeast Renal Research Institute	Chattanooga	Tennessee
United States	John H. Stroger Jr. Hospital of Cook County	Chicago	Illinois
United States	Clinical Research of South Florida	Coral Gables	Florida
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	LLC DBA AccessMD Clinical Research	Dayton	Ohio
United States	The Center for Diabetes and Endocrine Care	Hollywood	Florida
United States	17070 Red Oak dr Ste 103	Houston	Texas
United States	Community Medical Research Partners	Indianapolis	Indiana
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Kansas City VA Medical Center	Kansas City	Missouri
United States	Coral Research Clinic	Miami	Florida
United States	Genoma Research Group, Inc.	Miami	Florida
United States	Zablocki VAMC	Milwaukee	Wisconsin
United States	Creighton Diabetes Center	Omaha	Nebraska
United States	The Endocrine Medical Group, Inc	Orange	California
United States	Pines Clinical Research Inc.	Pembroke Pines	Florida
United States	Volunteer Medical Research	Port Charlotte	Florida
United States	McGuire VA Medical Center	Richmond	Virginia
United States	Dialysis West University Health System	San Atonio	Texas
United States	Advanced Arizona Clinical Research	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Genkyotex Innovation SAS

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czech Republic,  Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Erectile dysfunction	Changes in IEFF questionnaire assessing erectile dysfunction in patients presenting with these diabetic complications at baseline	Visits 5 (week 0), 8 (week 6), and 11 (week 12)	No
Other	Neuropathic pain	Changes in Visual Analog Scale (VAS) assessing neuropathic leg pain in patients presenting with these diabetic complications at baseline	Visits 5 (week 0), 8 (week 6), and 11 (week 12)	No
Primary	Albuminuria	Change in UACR from baseline to Visits 9, 10, and 11 (i.e. weeks 8, 10 and 12 of the treatment period, respectively)	Visits 4 (week -2), 5 (week 0), 6 (week 2), 7 (week 4), 8 (week 6), 9 (week 8), 10 (week 10), 11 (week 12), and 12 (week 16)	No
Secondary	Glucose metabolism	Change in HOMA-B, HOMA-IR and HbA1c from baseline	Visits 5 (week 0), 8 (week 6), and 11 (week 12)	No