Clinical trial NCT02010242: Safety and Efficacy of Oral GKT137831 in Patient With Type 2 Diabetes and Albuminuria
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus With Diabetic Nephropathy
Keywords: Type 2 diabetes
Proteinuria
Albuminuria
Lead sponsor: Calliditas Therapeutics AB
Sponsor class: INDUSTRY
First posted: 2013-12-12
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Albuminuria Absolute Value and Ratio to Baseline by Study Visit and Treatment Group
timeFrame: Visit 4 (week -2) to visit 11 (week 12)
Secondary outcomes:
measure: Glucose Metabolism by Homeostatic Model Assessment (HOMA)
timeFrame: Visits 5 (week 0), 8 (week 6), and 11 (week 12)
measure: Glucose Metabolism HbA1c
timeFrame: Visit 5 (week 0), 8 (week 6) and 11 (week 12)
measure: 24 Hours Albumin Excretion
timeFrame: Visits 5 (week 0) and 11 (week 12)
measure: 24 Hours Urine UACR
timeFrame: Visits 5 (week 0) and 11 (week 12)
measure: eGFR Change by Study Visit
timeFrame: 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:
measure: Erectile Dysfunction
timeFrame: Visits 5 (week 0), and 11 (week 12)
measure: Neuropathic Pain
timeFrame: Visits 5 (week 0), and 11 (week 12)
Locations:
city: Tucson
country: United States
facility: Advanced Arizona Clinical Research
state: Arizona
city: Orange
country: United States
facility: The Endocrine Medical Group, Inc
state: California
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Hollywood
country: United States
facility: The Center for Diabetes and Endocrine Care
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Miami
country: United States
facility: Genoma Research Group, Inc.
state: Florida
city: Miami
country: United States
facility: Coral Research Clinic
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Clinical Research Inc.
state: Florida
city: Port Charlotte
country: United States
facility: Volunteer Medical Research
state: Florida
city: Chicago
country: United States
facility: John H. Stroger Jr. Hospital of Cook County
state: Illinois
city: Indianapolis
country: United States
facility: Community Medical Research Partners
state: Indiana
city: Kansas City
country: United States
facility: Kansas City VA Medical Center
state: Missouri
city: Omaha
country: United States
facility: Creighton Diabetes Center
state: Nebraska
city: Dayton
country: United States
facility: LLC DBA AccessMD Clinical Research
state: Ohio
city: Chattanooga
country: United States
facility: Southeast Renal Research Institute
state: Tennessee
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: 17070 Red Oak dr Ste 103
state: Texas
city: San Antonio
country: United States
facility: Dialysis West University Health System
state: Texas
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Milwaukee
country: United States
facility: Zablocki VAMC
state: Wisconsin
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Geelong
country: Australia
facility: Deakin University school of medicine
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Baker Institute
state: Victoria
city: Ringwood East
country: Australia
facility: Maroondah ECRU
state: Victoria
city: Nedlands
country: Australia
facility: Captain Stirling Medical Centre
state: Western Australia
city: Vancouver
country: Canada
facility: Endocrine Research Inc.
state: British Columbia
city: Brampton
country: Canada
facility: LMC Diabetes & Endocrinology
state: Ontario
city: Kitchener
country: Canada
facility: Clinical Research Solutions
state: Ontario
city: Thornhill
country: Canada
facility: LMC Diabetes and Endocrinology
state: Ontario
city: Toronto
country: Canada
facility: Toronto East General Medical Centre
state: Ontario
city: Montreal
country: Canada
facility: Medpharmgene
state: Quebec
city: Huzova
country: Czechia
facility: Nemocnice Havlickuv Brod
city: Novy Bydzov
country: Czechia
facility: Oblastni nemocnice Jicin a.s.
city: Olomouc
country: Czechia
facility: Faculty Hospital and Palacky University Olomouc
city: Prague
country: Czechia
facility: Milan Kvapil s.r.o. diabetology ambulance
city: Praha
country: Czechia
facility: IKEM
city: Aschaffenburg
country: Germany
facility: Studienzentrum Haematologie/Onkologie/Diabeteologie
city: Elsterwerda
country: Germany
facility: ZKS Suedbrandenburg GmbH
city: Mainz
country: Germany
facility: IKFE - Institute for Clinical Research and Development
city: Munchen
country: Germany
facility: IDFM
city: Gdansk
country: Poland
facility: Centrum Badaa Klinicznych PI-House Sp. z o.o.
city: Krakow
country: Poland
facility: LANDA Specjalistyczne Gabinety Lekarskie
city: Opole
country: Poland
facility: Medicus w Opolu sp z o.o.
city: Poznan
country: Poland
facility: Praktyka Lekarska Ewa Krzyzagorska
city: Staszow
country: Poland
facility: KO-MED Centra Kliniczne Sp. z o.o.
city: Szczecin
country: Poland
facility: Department of Nephrology, Transplantationa and Internal Medicine
city: Warsaw
country: Poland
facility: Medica Pro Familia Sp. z o.o. S.K.A.
Study officials:
affiliation: Calliditas Therapeutics AB
name: Philippe Wiesel, MD
role: STUDY_DIRECTOR
References: