Canagliflozin Clinical Trials

What Is Canagliflozin?

Canagliflozin is an FDA-approved medication for type 2 diabetes. It is an oral drug that belongs to a class called sodium-glucose cotransporter 2 (SGLT2) inhibitors. Canagliflozin works by increasing the amount of sugar and salt that the kidneys remove from the body and excrete in the urine. This action helps to lower blood glucose levels in patients with type 2 diabetes. Studies have also shown that canagliflozin can help protect heart, kidney, and blood vessel function in these patients.

Beyond its approved use, canagliflozin is being investigated in clinical trials for various other conditions. These include studies exploring its effects on body weight and metabolism in people with type 2 diabetes who are overweight or obese. Research also examines its potential role in conditions like nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), for which there are currently no FDA-approved medicines. The drug is also being studied in healthy volunteers to understand its effects on glucose transport and overall safety.

Uses and Conditions Under Study

Canagliflozin is primarily studied for conditions related to glucose metabolism and its complications. The most significant area of research is type 2 diabetes mellitus, including "Diabetes Mellitus, Type 2", "Type 2 Diabetes Mellitus", "Type 2 Diabetes", and "Diabetes". These conditions are the focus of 57 trials, reflecting canagliflozin's role in managing high blood sugar by increasing glucose excretion through the kidneys.

Many trials, specifically 42 studies, involve "Healthy" or "Healthy Volunteers". These studies help researchers understand how canagliflozin works in the body, its safety profile, and its effects on metabolism in individuals without pre-existing conditions.

Given its impact on metabolism, canagliflozin is also being investigated for "Obesity", with 4 trials exploring its potential to affect body weight and metabolism. Additionally, its protective effects on the heart and kidneys are being examined in 3 trials for "Cardiovascular Diseases" and 2 trials for "Diabetic Nephropathy". The drug's mechanism of increasing salt and sugar loss in the urine suggests potential benefits for these related complications.

Other areas of investigation include conditions like nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), which are often linked to type 2 diabetes. While there are no approved treatments for NAFLD/NASH, canagliflozin's metabolic effects are being explored in this context. Some studies also assess canagliflozin's use as a sodium-glucose cotransporter 2 inhibitor during acute kidney disease.

Dosing

Canagliflozin is available in tablet form for oral administration. Clinical trials have investigated various strengths and dosing regimens for canagliflozin, often taken once daily.

Commonly studied doses include 100 mg once daily and 300 mg once daily. These doses are typically taken by mouth, often before the first meal of the day. Some studies have explored a starting dose of 100 mg once daily, with potential escalation to 300 mg once daily if tolerated.

Other strengths and frequencies examined in research settings include 50 mg, 150 mg, and 200 mg daily. Some trials have also investigated canagliflozin taken twice daily, such as 50 mg twice daily, 150 mg twice daily, or 300 mg twice daily. Canagliflozin is frequently studied in combination with other medications for type 2 diabetes, such as metformin, and has been evaluated in various patient populations, including those with different levels of kidney function.

Side Effects

Clinical trials involving over 12,500 patients taking Canagliflozin have identified common side effects. The most frequently reported adverse event was hypoglycemia, or low blood sugar, which occurred in 11.3% of patients taking Canagliflozin, compared to 10.8% on placebo. Urinary tract infections were reported in 9.3% of patients on Canagliflozin, compared to 8.2% on placebo.

Other common side effects included:

• Nasopharyngitis (common cold symptoms): 9.0% of patients taking Canagliflozin experienced this, compared to 9.4% on placebo.
• Upper respiratory tract infection: 7.4% of patients on Canagliflozin, compared to 8.0% on placebo.
• Back pain: 7.1% of patients on Canagliflozin, compared to 6.2% on placebo.
• Diarrhea: 5.7% of patients on Canagliflozin, compared to 6.9% on placebo.
• Bronchitis: 5.4% of patients on Canagliflozin, compared to 5.2% on placebo.

Clinical Trial Results

Canagliflozin has been studied in several clinical trials to evaluate its effectiveness in managing type 2 diabetes, promoting weight loss, and assessing cardiovascular and kidney outcomes.

Type 2 Diabetes Management

In a 12-week study (NCT00642278) for patients with type 2 diabetes, Canagliflozin significantly improved blood sugar control and led to weight loss. Patients taking Canagliflozin at various daily doses (50 mg to 300 mg twice daily) experienced an average reduction in HbA1c (a measure of long-term blood sugar) ranging from 0.70% to 0.95%. In comparison, patients on placebo saw a 0.22% reduction, and those on Sitagliptin saw a 0.74% reduction. Fasting plasma glucose also decreased by 0.9 to 1.5 mmol/L with Canagliflozin, while increasing by 0.2 mmol/L with placebo. Additionally, patients on Canagliflozin lost an average of 1.96 kg to 2.88 kg (2.3% to 3.4% of body weight), compared to a 0.78 kg (1.1%) loss on placebo.

A longer 52-week study (NCT00968812) comparing Canagliflozin to Glimepiride as an add-on to metformin showed that Canagliflozin 100 mg and 300 mg reduced HbA1c by 0.82% and 0.93% respectively, similar to Glimepiride's 0.81% reduction. However, Canagliflozin led to significant weight loss, with patients losing 4.2% to 4.7% of body weight, while patients on Glimepiride gained 1.0% of body weight. The trial also found a much lower rate of hypoglycemic events with Canagliflozin (4.9% to 5.6%) compared to Glimepiride (34.2%).

Cardiovascular and Kidney Benefits

The CANVAS study (NCT01032629) investigated Canagliflozin's effects on cardiovascular outcomes in patients with type 2 diabetes. Canagliflozin reduced the rate of major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal heart attack, and non-fatal stroke. The rate was 26.89 events per 1000 patient-years for Canagliflozin (total), compared to 30.36 events per 1000 patient-years for placebo. Canagliflozin also reduced systolic blood pressure by 3.70 to 4.91 mmHg and led to a 3.47% to 4.12% reduction in body weight over the study period, compared to a 0.50% reduction with placebo. Furthermore, Canagliflozin reduced the progression of albuminuria (a sign of kidney damage) in 18.3% to 20.2% of participants, compared to 24.0% on placebo.

Patients with Moderate Kidney Impairment

In a 26-week study (NCT01064414) of patients with type 2 diabetes and moderate kidney impairment, Canagliflozin 100 mg and 300 mg reduced HbA1c by 0.33% and 0.44% respectively, compared to a 0.03% reduction with placebo. A greater percentage of patients achieved an HbA1c below 7% with Canagliflozin (27.3% to 32.6%) compared to placebo (17.2%).

Weight Management in Overweight and Obese Patients Without Diabetes

A 12-week study (NCT00650806) in overweight and obese patients without diabetes showed that Canagliflozin helped with weight loss. Patients taking Canagliflozin 50 mg to 300 mg daily experienced an average weight loss of 1.9 kg to 2.8 kg (2.0% to 2.8% of body weight), compared to 1.1 kg (1.1%) with placebo. Additionally, 12.6% to 18.8% of patients on Canagliflozin lost at least 5% of their initial body weight, compared to 8.1% on placebo. Waist circumference also decreased by 1.4 cm to 2.9 cm with Canagliflozin, versus 1.2 cm with placebo.

Currently Recruiting Trials

Canagliflozin is currently being investigated in several clinical trials, exploring its potential benefits across a range of conditions. These studies aim to understand how this medication works and who might benefit most from its use.

• A Phase II, proof-of-concept study, NCT06913647, is assessing the effect of canagliflozin on peritoneal membrane function in patients with End-Stage Renal Disease (ESRD) and Chronic Kidney Disease (CKD) Stage 5D who are undergoing peritoneal dialysis. This trial, sponsored by McGill University Health Centre, aims to enroll 30 participants.
• For patients with metastatic high microsatellite instability (MSI-H) colorectal cancer, a Phase I trial, NCT07076823, is evaluating the safety and efficacy of canagliflozin. This study, sponsored by West China Hospital, plans to recruit 15 individuals.
• National Taiwan University Hospital is sponsoring a Phase II study, NCT06528405, to determine the efficacy and safety of SGLT2 inhibitors, including canagliflozin, in patients experiencing acute kidney disease. This trial is seeking to enroll 264 participants.
• The CANTOR SING study, NCT05427084, is a Phase II/III trial investigating canagliflozin's role in targeting vascular inflammation. This study, sponsored by Ottawa Heart Institute Research Corporation, compares 300 mg daily of canagliflozin against a placebo in 24 participants with Type 2 Diabetes and stable Coronary Artery Disease.
• Another Phase II, proof-of-concept study from McGill University Health Centre, NCT06182839, is examining the effect of canagliflozin on cardiac structure and function in patients with advanced renal disease, including those on maintenance dialysis. This trial aims to enroll 92 participants with ESRD, CKD Stage 4, or CKD Stage 5.
• The University of Colorado, Denver, is sponsoring a Phase II study, NCT05507892, focusing on the renal mechanism of SGLT2 inhibition with canagliflozin in patients with Type 2 Diabetes and Diabetic Kidney Disease. This study plans to include 40 participants.

Where to Participate

Clinical trials for canagliflozin are currently recruiting participants across two sites in the United States. These research sites are located in different cities and states, offering opportunities for participation in various regions.

• Aurora, Colorado
• Ann Arbor, Michigan

To be eligible for these studies, participants must generally be between 18 and 80 years old. All genders are welcome, but the trials are not designed for healthy volunteers or children.

Development Timeline

The extensive development journey for canagliflozin began on March 25, 2008, with the initiation of its first clinical trial. Since then, a robust research program has unfolded, encompassing a total of 128 trials and involving over 1.1 million participants globally. The latest trial is projected to conclude in July 2025.

Early investigations initially explored conditions such as Irritable Bowel Syndrome with Constipation and hyperphosphatemia. However, the research quickly expanded to focus on Type 2 Diabetes Mellitus, which became a primary area of study. Over time, the pipeline broadened significantly to include a wide array of conditions, such as various cardiovascular diseases, different stages of chronic kidney disease (CKD) including ESRD, obesity, and even certain cancers like breast and colorectal cancer.

A significant portion of this research has been driven by key sponsors, notably Janssen Research & Development, LLC, and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. The trials have progressed through all phases of development, with the majority being Phase 1 studies (52 trials), followed by Phase 4 (26 trials) and Phase 3 (21 trials), demonstrating a comprehensive approach from early exploration to post-market surveillance.