Clinical trial NCT01989754: A Study of the Effects of Canagliflozin (JNJ-28431754) on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus
Official title: A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Albuminuria
Keywords: Albuminuria
Canagliflozin
Cardiovascular outcomes
Type 2 Diabetes Mellitus
T2DM
JNJ-28431754
Antihyperglycemic Agent
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: The George Institute for Global Health, Australia
First posted: 2013-11-21
Enrollment: 5813
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effect of canagliflozin compared to placebo on progression of albuminuria in participants with Type 2 Diabetes Mellitus receiving standard care but with inadequate glycemic control and at elevated risk of cardiovascular events.

Detailed description: The study will be conducted in adult participants with Type 2 Diabetes Mellitus (T2DM), receiving standard of care for hyperglycemia and cardiovascular (CV) risk factors, who have either a history of a prior CV event or 2 or more risk factors for a CV event. Participants will be randomly assigned in a 1:1 ratio to canagliflozin or matching placebo to be taken once daily. Canagliflozin will be provided at a dose of 100 mg/day through Week 13 and then increased at the discretion of the investigator to a dose of 300 mg/day, if the participant requires additional glycemic control and is tolerating the 100 mg dose.

The study consists of a 2-week screening period and a double-blind treatment period lasting between 78 and 156 weeks; study completion is targeted for when the last subject randomized has approximately 78 weeks of follow-up or when 688 major adverse cardiovascular events are accumulated between CANVAS and CANVAS-R. A total of 5,700 participants are targeted to be recruited into the study. Participants can be either drug naïve to antihyperglycemic agents, using monotherapy, or using combination of antihyperglycemic therapy for the control of blood glucose levels.

The completion target was reached in February 2017.

Eligibility criteria: Inclusion Criteria:

* Must have a diagnosis of type 2 diabetes mellitus
* Must have inadequate diabetes control (as defined by glycosylated hemoglobin level \>=7.0% to \<=10.5% at screening)
* Greater than or equal to (\>=) 30 yrs old with history of cardiovascular (CV) event, or \>= 50 yrs old with high risk of CV events
* Must be either not on antihyperglycemic agents (AHA) therapy, or on AHA monotherapy, or combination AHA therapy with any approved agent for the control of blood glucose levels.

Exclusion Criteria

* History of diabetic ketoacidosis, type 1 diabetes mellitus, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
* History of one or more severe hypoglycemic episode within 6 months before screening
* History of hereditary glucose-galactose malabsorption or primary renal glucosuria
* Ongoing, inadequately controlled thyroid disorder
* Renal disease that required treatment with immunosuppressive therapy or a history of chronic dialysis or renal transplant
* Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident within 3 months before screening.

Primary outcomes:
measure: Progression of Albuminuria
timeFrame: Up to 3 years
Secondary outcomes:
measure: Composite of Cardiovascular (CV) Death Events or Hospitalization for Heart Failure
timeFrame: Approximately 3 years
measure: Cardiovascular (CV) Death
timeFrame: Approximately 3 years
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Carmichael
country: United States
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city: Concord
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city: Pismo Beach
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city: Roseville
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city: Mooresville
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city: Canal Fulton
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city: Franklin
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city: Lévis
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city: Quebec City
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city: Saint Marc Des Carriéres
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city: Sherbrooke
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city: Westmont
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city: Saskatoon
country: Canada
state: Saskatchewan
city: Baotou
country: China
city: Beijing
country: China
city: Hangzhou
country: China
city: Jinan
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city: Shenyang
country: China
city: Wuxi
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city: Beroun
country: Czechia
city: Ostrava
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city: Plzen
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city: Praha 10
country: Czechia
city: Praha 1
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city: Praha 4
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city: La Rochelle Cedex 1
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city: Palma De Mallorca
country: Spain
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country: Spain
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country: Spain
city: Sant Joan D'Alacant
country: Spain
city: Santa Cruz De Tenerife
country: Spain
city: Santiago De Compostela
country: Spain
city: Segovia
country: Spain
city: Sevilla N/A
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Viladecans
country: Spain
city: Borås
country: Sweden
city: Goteborg
country: Sweden
city: Helsingborg
country: Sweden
city: Karlstad
country: Sweden
city: Linköping
country: Sweden
city: Lund
country: Sweden
city: Malmo
country: Sweden
city: Stockholm
country: Sweden
city: Uddevalla
country: Sweden
city: Uppsala
country: Sweden
city: Vallingby
country: Sweden
city: Västra Frölunda
country: Sweden
city: Kaohsiung County
country: Taiwan
city: Taichung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Tiachung
country: Taiwan
city: Xindian
country: Taiwan
city: Cherkasy
country: Ukraine
city: Chernivtsy
country: Ukraine
city: Dnipropetrovsk
country: Ukraine
city: Ivan-Frankivsk
country: Ukraine
city: Ivano-Frankovsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kharkov
country: Ukraine
city: Kiev
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Odesa
country: Ukraine
city: Odessa
country: Ukraine
city: Poltava
country: Ukraine
city: Sumy
country: Ukraine
city: Ternopil
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Vinnitsa
country: Ukraine
city: Vinnytsya
country: Ukraine
city: Zaporizhzhia
country: Ukraine
city: Zaporizhzhya
country: Ukraine
city: Addlestone
country: United Kingdom
city: Belfast
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Blackburn
country: United Kingdom
city: Bristol
country: United Kingdom
city: Bury St Edmunds
country: United Kingdom
city: Chesterfield
country: United Kingdom
city: Derby
country: United Kingdom
city: Doncaster
country: United Kingdom
city: Ipswich
country: United Kingdom
city: Leicester
country: United Kingdom
city: Liverpool
country: United Kingdom
city: Manchester
country: United Kingdom
city: Salford
country: United Kingdom
city: Taunton
country: United Kingdom
city: Torquay
country: United Kingdom
city: Truro
country: United Kingdom
city: Wellingborough
country: United Kingdom
city: Welwyn Garden City
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
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citation: Zhou Z, Jardine M, Perkovic V, Matthews DR, Mahaffey KW, de Zeeuw D, Fulcher G, Desai M, Oh R, Simpson R, Watts NB, Neal B. Canagliflozin and fracture risk in individuals with type 2 diabetes: results from the CANVAS Program. Diabetologia. 2019 Oct;62(10):1854-1867. doi: 10.1007/s00125-019-4955-5. Epub 2019 Aug 10.
citation: Figtree GA, Radholm K, Barrett TD, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Matthews DR, Shaw W, Neal B. Effects of Canagliflozin on Heart Failure Outcomes Associated With Preserved and Reduced Ejection Fraction in Type 2 Diabetes Mellitus. Circulation. 2019 May 28;139(22):2591-2593. doi: 10.1161/CIRCULATIONAHA.119.040057. Epub 2019 Mar 17. No abstract available.
citation: Zhou Z, Lindley RI, Radholm K, Jenkins B, Watson J, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Shaw W, Oh R, Desai M, Matthews DR, Neal B. Canagliflozin and Stroke in Type 2 Diabetes Mellitus. Stroke. 2019 Feb;50(2):396-404. doi: 10.1161/STROKEAHA.118.023009.
citation: Neuen BL, Ohkuma T, Neal B, Matthews DR, de Zeeuw D, Mahaffey KW, Fulcher G, Desai M, Li Q, Deng H, Rosenthal N, Jardine MJ, Bakris G, Perkovic V. Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function. Circulation. 2018 Oct 9;138(15):1537-1550. doi: 10.1161/CIRCULATIONAHA.118.035901.
citation: Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Erondu N, Shaw W, Barrett TD, Weidner-Wells M, Deng H, Matthews DR, Neal B. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol. 2018 Sep;6(9):691-704. doi: 10.1016/S2213-8587(18)30141-4. Epub 2018 Jun 21.
citation: Wittbrodt ET, Eudicone JM, Bell KF, Enhoffer DM, Latham K, Green JB. Eligibility varies among the 4 sodium-glucose cotransporter-2 inhibitor cardiovascular outcomes trials: implications for the general type 2 diabetes US population. Am J Manag Care. 2018 Apr;24(8 Suppl):S138-S145.
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