An Efficacy, Safety, and Tolerability Study of Canagliflozin in Patients With Type 2 Diabetes Mellitus Who Have Moderate Renal Impairment

NCT ID: NCT01064414

Last Updated: 2013-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 272 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2012-08-31

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of 2 different doses of canagliflozin compared with placebo in patients with type 2 diabetes mellitus who have reduced kidney function.

Detailed Description

This is a randomized (study drug assigned by chance), double blind (neither the patient or the study doctor will know the name of the assigned treatment), parallel-group, 3-arm (patients will be assigned to 1 of 3 treatment groups) multicenter study to determine the efficacy, safety, and tolerability of 2 different doses of canagliflozin (100 mg and 300 mg) compared to placebo (a pill that looks like all the other treatments but has no real medicine) in patients with type 2 diabetes mellitus (T2DM) who have renal impairment (reduced kidney function) and who are not achieving an adequate response from current therapy to control their diabetes. Canagliflozin (also referred to as JNJ-28431754) is a drug that is being tested to see if it may be useful in treating patients diagnosed with T2DM. Approximately 240 patients will participate in the study for approximately 63 to 72 weeks, depending on the length of the pretreatment phase. The study will consist of a pretreatment phase, a 52 week double blind treatment phase, and a posttreatment phase. During the pretreatment phase, screening evaluations will be performed to see if patients meet the entry criteria for the study. In addition, routine clinical procedures will be performed (physical examination, vital signs measurements, and an electrocardiogram [ECG]), a blood and urine sample will be collected for routine clinical laboratory tests, and all antihyperglycemic therapy taken by patients will be reviewed. Patients who meet entrance criteria for the study and who currently take a stable antihyperglycemic agent (AHA) regimen according to the local prescribing information will be eligible for inclusion in the study. Patients who meet entrance criteria for the study but who are not taking a stable AHA regimen according to the local prescribing information will enter an AHA adjustment period that may last for up to 12 weeks. Patients will receive once daily treatment with study drug in addition to their current stable diabetes regimen (eg, diet, exercise, and medication therapy). Patients will continue to take their assigned treatment for 52 weeks (includes a 26-week core double-blind treatment period and a 26-week extension double-blind treatment period). During the study, if a patient's blood sugar remains high despite treatment with study drug in combination with their other antidiabetic agents, the study physician will modify the patient's treatment. If patients take insulin and experience low blood sugar (hypoglycemia), the dose of insulin may be modified. During the study, patients will be monitored for safety by review of adverse events, results from safety laboratory tests (including chemistry, hematology, and urinalysis), ECGs, vital signs measurements, body weight, physical examinations, self-monitored blood glucose, and collection of potential hypoglycemic episodes reported by patients on diary cards. The safety of patients in this study will also be monitored by a company internal Medical Safety Review Committee (MSRC). An Independent Data Monitoring Committee (IDMC) will evaluate cardiovascular (CV) events that are reported across the entire clinical development program for canagliflozin. Patients who complete the Week 52 visit or who discontinue treatment early and are withdrawn from the study will have end-of-study evaluations performed and a follow-up telephone interview conducted by study personnel approximately 30 days (but no more than 42 days) after the last dose of study drug to collect any serious adverse events that occurred since their last study visit. The primary outcome measures in the study are to assess the effect of canagliflozin relative to placebo on hemoglobin A1c (HbA1c, a blood test used to measure the control of diabetes) after 26 weeks of treatment and to assess the safety and tolerability of canagliflozin from time of signed informed consent to study end (includes up to 30 days following the last dose of study drug). All patients will take a single-blind placebo capsule once daily for 2 weeks before randomization to double-blind study drug. After randomization, patients will take one capsule of canagliflozin (either 100 mg or 300 mg) or matching placebo orally (by mouth) with liquid once daily for 52 weeks before the first meal each day except on days when fasting or pharmacokinetic blood samples are collected in which case study drug will be taken after the visit immediately before the patient's next meal.

Conditions

Diabetes Mellitus, Type 2; Renal Insufficiency

Keywords

Canagliflozin; JNJ 28431754; Placebo; Sodium-Glucose Transporter 2; hemoglobin A1c protein, Blood Glucose; reduced kidney function, Type 2 diabetes mellitus

Study Design

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

Study Groups

Canagliflozin 100 mg

Each patient will receive 100 mg of canagliflozin once daily for 52 weeks.

Group Type: EXPERIMENTAL

Canagliflozin

Intervention Type: DRUG

One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) once daily for 52 weeks in addition to the patient's AHA regimen used in accordance with local prescribing information

Canagliflozin 300 mg

Each patient will receive 300 mg of canagliflozin once daily for 52 weeks.

Group Type: EXPERIMENTAL

Canagliflozin

Intervention Type: DRUG

One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) once daily for 52 weeks in addition to the patient's AHA regimen used in accordance with local prescribing information

Placebo

Each patient will receive matching placebo once daily for 52 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One matching placebo capsule orally once daily for 52 weeks in addition to the patient's AHA regimen used in accordance with local prescribing information

Interventions

Canagliflozin

One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) once daily for 52 weeks in addition to the patient's AHA regimen used in accordance with local prescribing information

Intervention Type: DRUG

Placebo

One matching placebo capsule orally once daily for 52 weeks in addition to the patient's AHA regimen used in accordance with local prescribing information

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with T2DM not on an AHA or on any AHA in monotherapy or combination therapy (including oral or non oral agents)
• Patients with reduced kidney function

Exclusion Criteria

• History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
• Have proliferative diabetic retinopathy for which treatment is planned during the course of the study
• Kidney disease that required treatment with immunosuppressive therapy, history of dialysis or kidney transplant, presence of nephrotic syndrome (eg, severe proteinuria with hypoalbuminemia and/or edema), or inflammatory kidney disease
• Receiving anti hypertensive or anti-hyperlipidemic therapy not on a stable regimen
• History of a severe hypoglycemic episode within 6 months before screening

• Minimum Eligible Age: 25 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 C. Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Concord, California, United States

Fountain Valley, California, United States

San Diego, California, United States

Denver, Colorado, United States

Pembroke Pines, Florida, United States

Tampa, Florida, United States

West Palm Beach, Florida, United States

Augusta, Georgia, United States

Nampa, Idaho, United States

Baton Rouge, Louisiana, United States

Jackson, Mississippi, United States

Picayune, Mississippi, United States

Chesterfield, Missouri, United States

Las Vegas, Nevada, United States

Albuquerque, New Mexico, United States

Durham, North Carolina, United States

Canal Fulton, Ohio, United States

Cincinnati, Ohio, United States

Columbus, Ohio, United States

Zanesville, Ohio, United States

Oklahoma City, Oklahoma, United States

Meridian, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

North Charleston, South Carolina, United States

Salt Lake City, Utah, United States

Fairfax, Virginia, United States

Camperdown, , Australia

Gosford, , Australia

Parkville, , Australia

Reservoir, , Australia

Aalst, , Belgium

Bonheiden, , Belgium

Brussels, , Belgium

Liège, , Belgium

Sint-Niklaas, , Belgium

Turnhout, , Belgium

São Paulo, , Brazil

Vancouver, British Columbia, Canada

Victoria, British Columbia, Canada

Antigonish, Nova Scotia, Canada

Sydney, Nova Scotia, Canada

Hamilton, Ontario, Canada

London, Ontario, Canada

Smiths Falls, Ontario, Canada

Thornhill, Ontario, Canada

Montreal, Quebec, Canada

Calgary, , Canada

Corbeil-Essonnes, , France

La Rochelle Cedex 1 Poitou-Cha, , France

Le Creusot, , France

Nantes, , France

Pierre-Bénite, , France

Vandœuvre-lès-Nancy, , France

Vénissieux, , France

Dormagen, , Germany

Dortmund, , Germany

Dresden, , Germany

Einbeck, , Germany

Freiburg im Breisgau, , Germany

Kassel, , Germany

München, , Germany

Schkeuditz, , Germany

Würzburg, , Germany

Aurangabad, , India

Madurai, , India

Pune, , India

Daugavpils, , Latvia

Ogre, , Latvia

Riga, , Latvia

Jalan Cheras N/A, , Malaysia

Kajang, , Malaysia

Kuala Lumpur, , Malaysia

Pulau Pinang, , Malaysia

Aguascalientes, , Mexico

Culiacán, , Mexico

Morelia, , Mexico

Zapopan, , Mexico

Auckland, , New Zealand

Christchurch, , New Zealand

Dunedin Nz, , New Zealand

Nz, , New Zealand

Lublin, , Poland

Warsaw, , Poland

Łask, , Poland

Bucharest, , Romania

Târgovişte, , Romania

Chelyabinsk, , Russia

Kirov, , Russia

Kursk, , Russia

Moscow, , Russia

Nizhny Novgorod, , Russia

Petrozavodsk, , Russia

Rostov-on-Don, , Russia

Saint Petersburg, , Russia

Yaroslavl, , Russia

Parow, Cape Town, , South Africa

Pretoria, , South Africa

Somerset West, , South Africa

Seognam-Si, Kyungki-Do, , South Korea

Seoul, , South Korea

Barcelona, , Spain

Ciudad Real, , Spain

Madrid, , Spain

San Sebastián de los Reyes, , Spain

Santa Cruz de Tenerife, , Spain

Valencia, , Spain

Countries

Hong Kong; United States; Australia; Belgium; Brazil; Canada; France; Germany; India; Latvia; Malaysia; Mexico; New Zealand; Poland; Romania; Russia; South Africa; South Korea; Spain

References

Watts NB, Bilezikian JP, Usiskin K, Edwards R, Desai M, Law G, Meininger G. Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus. J Clin Endocrinol Metab. 2016 Jan;101(1):157-66. doi: 10.1210/jc.2015-3167. Epub 2015 Nov 18.

Reference Type: DERIVED

PMID: 26580237 (View on PubMed)

Weir MR, Kline I, Xie J, Edwards R, Usiskin K. Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR). Curr Med Res Opin. 2014 Sep;30(9):1759-68. doi: 10.1185/03007995.2014.919907. Epub 2014 May 22.

Reference Type: DERIVED

PMID: 24786834 (View on PubMed)

Nyirjesy P, Sobel JD, Fung A, Mayer C, Capuano G, Ways K, Usiskin K. Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. Curr Med Res Opin. 2014 Jun;30(6):1109-19. doi: 10.1185/03007995.2014.890925. Epub 2014 Feb 21.

Reference Type: DERIVED

PMID: 24517339 (View on PubMed)

Other Identifiers

28431754DIA3004

Identifier Type: OTHER

Identifier Source: secondary_id

CR017008

Identifier Type: -

Identifier Source: org_study_id