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

NCT ID: NCT01809327

Last Updated: 2017-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1186 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-04
• Study Completion Date: 2014-12-02

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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Canagliflozin 100 mg

Participants will receive one 100 mg canagliflozin capsule before the morning meal and one matching placebo capsule with the evening meal plus placebo tablets with the evening meal (to match the metformin XR tablets administered in other treatment arms) for 26 weeks.

Group Type: EXPERIMENTAL

Canagliflozin 100 mg

Intervention Type: DRUG

One 100 mg capsule taken orally (by mouth) once daily either before the morning meal (for the Canagliflozin 100 mg arm) or with the evening meal (for the Canagliflozin 100 mg + Metformin XR arm).

Canagliflozin 300 mg

Participants will receive one 300 mg canagliflozin capsule before the morning meal and one matching placebo capsule with the evening meal plus placebo tablets with the evening meal (to match the metformin XR tablets administered in other treatment arms) for 26 weeks.

Group Type: EXPERIMENTAL

Canagliflozin 300 mg

Intervention Type: DRUG

One 300 mg capsule taken orally (by mouth) once daily either before the morning meal (for the Canagliflozin 300 mg arm) or with the evening meal (for the Canagliflozin 300 mg + Metformin XR arm).

Metformin XR

Participants will receive metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal, plus one placebo capsule before the morning meal and one placebo capsule with the evening meal (to match the canagliflozin capsules administered in other treatment arms) for 26 weeks.

Group Type: EXPERIMENTAL

Metformin XR

Intervention Type: DRUG

One 500 mg tablet (Day 1 up to week 1); two 500 mg tablets (Week 1 up to Week 3); three 500 mg tablets (Week 3 to Week 6); four 500 mg tablets (Week 6 to Week 9). Tablets will be administered with the evening meal.

Canagliflozin 100 mg + Metformin XR

Participants will receive one 100 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.

Group Type: EXPERIMENTAL

Canagliflozin 100 mg

Intervention Type: DRUG

One 100 mg capsule taken orally (by mouth) once daily either before the morning meal (for the Canagliflozin 100 mg arm) or with the evening meal (for the Canagliflozin 100 mg + Metformin XR arm).

Metformin XR

Intervention Type: DRUG

One 500 mg tablet (Day 1 up to week 1); two 500 mg tablets (Week 1 up to Week 3); three 500 mg tablets (Week 3 to Week 6); four 500 mg tablets (Week 6 to Week 9). Tablets will be administered with the evening meal.

Canagliflozin 300 mg + Metformin XR

Participants will receive one 300 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.

Group Type: EXPERIMENTAL

Canagliflozin 300 mg

Intervention Type: DRUG

One 300 mg capsule taken orally (by mouth) once daily either before the morning meal (for the Canagliflozin 300 mg arm) or with the evening meal (for the Canagliflozin 300 mg + Metformin XR arm).

Metformin XR

Intervention Type: DRUG

One 500 mg tablet (Day 1 up to week 1); two 500 mg tablets (Week 1 up to Week 3); three 500 mg tablets (Week 3 to Week 6); four 500 mg tablets (Week 6 to Week 9). Tablets will be administered with the evening meal.

Interventions

Canagliflozin 100 mg

One 100 mg capsule taken orally (by mouth) once daily either before the morning meal (for the Canagliflozin 100 mg arm) or with the evening meal (for the Canagliflozin 100 mg + Metformin XR arm).

Intervention Type: DRUG

Canagliflozin 300 mg

One 300 mg capsule taken orally (by mouth) once daily either before the morning meal (for the Canagliflozin 300 mg arm) or with the evening meal (for the Canagliflozin 300 mg + Metformin XR arm).

Intervention Type: DRUG

Metformin XR

One 500 mg tablet (Day 1 up to week 1); two 500 mg tablets (Week 1 up to Week 3); three 500 mg tablets (Week 3 to Week 6); four 500 mg tablets (Week 6 to Week 9). Tablets will be administered with the evening meal.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Birmingham, Alabama, United States

Phoenix, Arizona, United States

Encinitas, California, United States

Newport Beach, California, United States

Northridge, California, United States

Norwalk, California, United States

Rancho Cucamonga, California, United States

Walnut Creek, California, United States

Denver, Colorado, United States

Northglenn, Colorado, United States

Hialeah, Florida, United States

Miami, Florida, United States

New Port Richey, Florida, United States

Opa-locka, Florida, United States

Perry, Georgia, United States

Evansville, Indiana, United States

Mandeville, Louisiana, United States

Metairie, Louisiana, United States

Sunset, Louisiana, United States

Flint, Michigan, United States

Kalamazoo, Michigan, United States

Royal Oak, Michigan, United States

Troy, Michigan, United States

Olive Branch, Mississippi, United States

Picayune, Mississippi, United States

Albuquerque, New Mexico, United States

West Seneca, New York, United States

Hickory, North Carolina, United States

Mooresville, North Carolina, United States

Franklin, Ohio, United States

Mason, Ohio, United States

Perrysburg, Ohio, United States

Zanesville, Ohio, United States

Oklahoma City, Oklahoma, United States

Yukon, Oklahoma, United States

Tualatin, Oregon, United States

Fleetwood, Pennsylvania, United States

Norristown, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Rapid City, South Dakota, United States

Nashville, Tennessee, United States

Austin, Texas, United States

Bellaire, Texas, United States

Dallas, Texas, United States

Houston, Texas, United States

Pearland, Texas, United States

Plano, Texas, United States

Bountiful, Utah, United States

Salt Lake City, Utah, United States

Danville, Virginia, United States

Norfolk, Virginia, United States

Richmond, Virginia, United States

Buenos Aires, , Argentina

Ciudad Autonoma Buenos Aires, , Argentina

Córdoba, , Argentina

Mar del Plata, , Argentina

Morón, , Argentina

Rosario, , Argentina

Zárate, , Argentina

Passo Fundo, , Brazil

São Paulo, , Brazil

Kroměříž, , Czechia

Pardubice, , Czechia

Prague, , Czechia

Uničov, , Czechia

Balatonfüred, , Hungary

Budapest, , Hungary

Eger, , Hungary

Szikszó, , Hungary

Zalaegerszeg, , Hungary

Celaya, , Mexico

Durango, , Mexico

Guadalajara, , Mexico

México, , Mexico

Monterrey, , Mexico

Pachuca, , Mexico

Tampico, , Mexico

Carolina, , Puerto Rico

Ponce, , Puerto Rico

San Juan, , Puerto Rico

Trujillo Alto, , Puerto Rico

Bacau, , Romania

Brasov, , Romania

Bucharest, , Romania

Oradea, , Romania

Tg Mures, , Romania

Arkhangelsk, , Russia

Barnaul, , Russia

Chelyabinsk, , Russia

Kemerovo, , Russia

Moscow, , Russia

Penza, , Russia

Rostov-on-Don, , Russia

Saint Petersburg, , Russia

Samara, , Russia

Saratov, , Russia

Smolensk, , Russia

Syktyvkar, , Russia

Tomsk, , Russia

Tyumen, , Russia

Voronezh, , Russia

Banská Bystrica, , Slovakia

Bratislava, , Slovakia

Malacky, , Slovakia

Prešov, , Slovakia

Rimavská Sobota, , Slovakia

Šahy, , Slovakia

Trebišov, , Slovakia

Cape Town, , South Africa

Durban, , South Africa

Halfway, , South Africa

Johannesburg, , South Africa

Soweto, Johannesburg, , South Africa

Worcester, , South Africa

Goyang-si, , South Korea

Seoul, , South Korea

Suwon, , South Korea

Cherkasy, , Ukraine

Dnipro, , Ukraine

Donetsk, , Ukraine

Ivano-Frankivsk, , Ukraine

Kharkiv, , Ukraine

Kiev, , Ukraine

Kyiv, , Ukraine

Lviv, , Ukraine

Odesa, , Ukraine

Poltava, , Ukraine

Sumy, , Ukraine

Zaporizhzhya, , Ukraine

Countries

United States; Argentina; Brazil; Czechia; Hungary; Mexico; Puerto Rico; Romania; Russia; Slovakia; South Africa; South Korea; Ukraine

References

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.

Reference Type: DERIVED

PMID: 26786577 (View on PubMed)

Other Identifiers

28431754DIA3011

Identifier Type: OTHER

Identifier Source: secondary_id

2011-000400-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR100034

Identifier Type: -

Identifier Source: org_study_id