Clinical trial NCT01809327: A Study to Evaluate the Effectiveness, Safety, and Tolerability of Canagliflozin in Combination With Metformin in the Treatment of Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control With Diet and Exercise
Official title: A Randomized, Double-Blind, 5-Arm, Parallel-Group, 26-Week, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin in Combination With Metformin as Initial Combination Therapy in the Treatment of Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control With Diet and Exercise
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes Mellitus, Type 2
Diabetes Mellitus
Canagliflozin (JNJ-28431754)
Metformin
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2013-03-12
Enrollment: 1186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
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 effectiveness of the co-administration of canagliflozin and metformin extended release (XR) compared with canagliflozin alone, and metformin XR alone in patients with type 2 diabetes mellitus with inadequate control despite treatment with diet and exercise. The safety and tolerability of canagliflozin will also be assessed.

Detailed description: This study will be a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), active-controlled (one of the treatments is an established effective treatment for type 2 diabetes mellitus), parallel-group (each group of participants will be treated at the same time), 5-arm (groups), multicenter study. Approximately 1,200 participants will be randomly assigned to the 5 treatment arms in a 1:1:1:1:1 ratio for 26 weeks.

Eligibility criteria: Inclusion Criteria:

* Must have type 2 diabetes mellitus with inadequate glycemic control on diet and exercise
* Not on antihyperglycemic agent therapy (at least 12 weeks before screening) and have a screening visit fingerstick glycated hemoglobin (HbA1c) of more than or equal to 7 percent and less than or equal to 12.5 percent
* Have a screening visit HbA1c of more than or equal to 7.5 percent and less than or equal to 12 percent as determined by the central laboratory
* Must have a fasting plasma glucose of less than or equal to 300 mg/dL (16.7 mmol/L) prior to randomization
* Must have a fasting fingerstick glucose of greater than 120 mg/dL (6.7 mmol/L) performed at home or at the study center prior to randomization

Exclusion Criteria:

* History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
* Fasting C-peptide less than 0.70 ng/mL (0.23 nmol/L) in participants for whom the investigator cannot reasonably exclude T1DM based upon clinical evaluation
* Repeated (2 or more over a 1 week period) fasting self-monitored blood glucose measurements more than 300 mg/dL (16.7 mmol/L) prior to randomization, despite reinforcement of diet and exercise counseling
* History of hereditary glucose-galactose malabsorption or primary renal glucosuria
* Has history of, or currently active, illness considered to be clinically significant by the Investigator or any other illness that the Investigator considers should exclude the patient from the study or that could interfere with the interpretation of the study results

Primary outcomes:
measure: Change in Glycated Hemoglobin (HbA1c) From Baseline at Week 26
timeFrame: Day 1 (Baseline) and Week 26
Secondary outcomes:
measure: Percent Change in Body Weight From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Percentage of Participants With Glycated Hemoglobin (HbAIc) Less Than 7 Percent at Week 26
timeFrame: Week 26
measure: Change in Systolic Blood Pressure From Baseline at Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Fasting High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Triglycerides From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Number of Participants With Treatment Emergent Adverse Events (AEs)
timeFrame: Up to 30 weeks of last study drug administration
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Encinitas
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Northridge
country: United States
state: California
city: Norwalk
country: United States
state: California
city: Rancho Cucamonga
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Northglenn
country: United States
state: Colorado
city: Hialeah
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Opa-locka
country: United States
state: Florida
city: Perry
country: United States
state: Georgia
city: Evansville
country: United States
state: Indiana
city: Mandeville
country: United States
state: Louisiana
city: Metairie
country: United States
state: Louisiana
city: Sunset
country: United States
state: Louisiana
city: Flint
country: United States
state: Michigan
city: Kalamazoo
country: United States
state: Michigan
city: Royal Oak
country: United States
state: Michigan
city: Troy
country: United States
state: Michigan
city: Olive Branch
country: United States
state: Mississippi
city: Picayune
country: United States
state: Mississippi
city: Albuquerque
country: United States
state: New Mexico
city: West Seneca
country: United States
state: New York
city: Hickory
country: United States
state: North Carolina
city: Mooresville
country: United States
state: North Carolina
city: Franklin
country: United States
state: Ohio
city: Mason
country: United States
state: Ohio
city: Perrysburg
country: United States
state: Ohio
city: Zanesville
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Yukon
country: United States
state: Oklahoma
city: Tualatin
country: United States
state: Oregon
city: Fleetwood
country: United States
state: Pennsylvania
city: Norristown
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Rapid City
country: United States
state: South Dakota
city: Nashville
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Bellaire
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Pearland
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: Bountiful
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Danville
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Buenos Aires
country: Argentina
city: Ciudad Autonoma Buenos Aires
country: Argentina
city: Ciudad Autonoma De Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Mar Del Plata
country: Argentina
city: Moron
country: Argentina
city: Rosario
country: Argentina
city: Zarate
country: Argentina
city: Passo Fundo
country: Brazil
city: Sao Paulo
country: Brazil
city: São Paulo
country: Brazil
city: Kromeriz
country: Czechia
city: Pardubice
country: Czechia
city: Praha 8
country: Czechia
city: Praha
country: Czechia
city: Unicov
country: Czechia
city: Balatonfured
country: Hungary
city: Budapest
country: Hungary
city: Eger
country: Hungary
city: Szikszó
country: Hungary
city: Zalaegerszeg
country: Hungary
city: Goyang-Si
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Suwon
country: Korea, Republic of
city: Celaya
country: Mexico
city: Durango
country: Mexico
city: Guadalajara
country: Mexico
city: Mexico
country: Mexico
city: Monterrey
country: Mexico
city: Pachuca De Soto
country: Mexico
city: Tampico
country: Mexico
city: Carolina
country: Puerto Rico
city: Ponce
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: Trujillo Alto
country: Puerto Rico
city: Bacau
country: Romania
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Oradea
country: Romania
city: Tg Mures
country: Romania
city: Arkhangelsk
country: Russian Federation
city: Barnaul
country: Russian Federation
city: Chelyabinsk
country: Russian Federation
city: Kemerovo
country: Russian Federation
city: Moscow
country: Russian Federation
city: Penza
country: Russian Federation
city: Rostov-On-Don
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Samara
country: Russian Federation
city: Saratov
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: Syktyvkar
country: Russian Federation
city: Tomsk
country: Russian Federation
city: Tyumen
country: Russian Federation
city: Voronezh
country: Russian Federation
city: Banska Bystrica
country: Slovakia
city: Bratislava
country: Slovakia
city: Malacky
country: Slovakia
city: Presov
country: Slovakia
city: Rimavska Sobota
country: Slovakia
city: Sahy
country: Slovakia
city: Trebisov
country: Slovakia
city: Cape Town
country: South Africa
city: Durban
country: South Africa
city: Halfway
country: South Africa
city: Johannesburg N/A
country: South Africa
city: Johannesburg
country: South Africa
city: Soweto, Johannesburg
country: South Africa
city: Worcester
country: South Africa
city: Cherkasy
country: Ukraine
city: Dnepropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Ivano Frankivsk
country: Ukraine
city: Kharkov
country: Ukraine
city: Kiev
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Odesa
country: Ukraine
city: Poltava
country: Ukraine
city: Sumy
country: Ukraine
city: Zaporozhye
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Rosenstock J, Chuck L, Gonzalez-Ortiz M, Merton K, Craig J, Capuano G, Qiu R. Initial Combination Therapy With Canagliflozin Plus Metformin Versus Each Component as Monotherapy for Drug-Naive Type 2 Diabetes. Diabetes Care. 2016 Mar;39(3):353-62. doi: 10.2337/dc15-1736. Epub 2016 Jan 19.