Clinical Trials

Date: 2017-06-10

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the American Diabetes Association Scientific Sessions

Company: Merck&Co (USA - NJ) - Pfizer (USA - NY)

Product: ertugliflozin

Action mechanism: SGLT2 inhibitor.

Disease: type 2 diabetes

Therapeutic area: Metabolic diseases

Country:

Trial details:

• Ertugliflozin is being investigated in the VERTIS clinical development program, which is comprised of nine Phase 3 trials in approximately 12,600 adults with type 2 diabetes.
• VERTIS MET is a 26-week study evaluating the efficacy and safety of ertugliflozin in combination with metformin, compared with placebo and metformin, in adults with type 2 diabetes uncontrolled on metformin monotherapy.
• VERTIS SITA is a 26-week study comparing the efficacy and safety of initial combination therapy with ertugliflozin and Merck’s DPP-4 inhibitor Januvia® (sitagliptin) with placebo.

Latest news:

• • On June 10, 2017, Merck&Co in partnership with Pfizer announced that two Phase 3 studies (VERTIS MET and VERTIS SITA) of ertugliflozin, an investigational oral SGLT-2 inhibitor in development to help improve glycemic control in adults with type 2 diabetes, met their primary endpoints. In the studies, both doses of ertugliflozin tested (5 mg and 15 mg daily) achieved statistically significant reductions in A1C, a measure of average blood glucose over a two- to three-month timeframe, when added to metformin or in initial co-administration with sitagliptin. The results of these studies, along with 52-week extension data from three other studies in the VERTIS clinical development program of ertugliflozin, will be presented at the 77th Scientific Sessions of the American Diabetes Association (ADA) in San Diego.
• VERTIS MET  (1168-P) In this randomized, double-blind 26-week investigational multicenter study, 621 patients with type 2 diabetes and a baseline A1C of 7.0 – 10.5 percent, who were inadequately controlled with metformin monotherapy (greater or equal to 1,500 mg/day for more than or equal to 8 weeks), were randomized to receive placebo, ertugliflozin 5 mg/day or ertugliflozin 15 mg/day in a 1:1:1 ratio, as an add-on therapy to metformin. In addition to meeting the study’s primary endpoint of improved blood glucose control at 26 weeks, ertugliflozin in combination with metformin also met a key secondary endpoint in the study, as significantly more patients taking ertugliflozin 5 mg and 15 mg in combination with metformin achieved the ADA’s recommended A1C treatment goal of less than 7.0 percent (35.3 percent and 40.0 percent, respectively) compared with placebo and metformin (15.8 percent) (p<0.001, for both comparisons based on adjusted odds ratio comparisons). The following statistically significant placebo-adjusted reductions were observed for the primary and additional key secondary endpoints for ertugliflozin added to metformin:
• A1C: 0.7 percent (5 mg) and 0.9 percent (15 mg) (p<0.001 for both comparisons);
• FPG: 26.7 mg/dL (5 mg) and 38.3 mg/dL (15 mg) (p<0.001 for both comparisons);
• Body weight: 3.7 lbs (1.7 kg) (5 mg) and 3.5 lbs (1.6 kg) (15 mg) (p<0.001 for both comparisons);
• SBP: 3.7 mmHg (5 mg) (p=0.002) and 4.5 mmHg (15 mg) (p<0.001); and
• DBP: 1.8 mmHg (5 mg) (p=0.013) and 2.4 mmHg (15 mg) (p=0.001).
• The incidence of adverse events was 42.5 percent, 50.2 percent and 45.0 percent in the ertugliflozin 5 mg and metformin, ertugliflozin 15 mg and metformin, and placebo and metformin groups, respectively. A higher incidence of genital mycotic infections in females was observed in patients taking ertugliflozin 5 mg (5.5 percent) and 15 mg (6.3 percent) versus placebo (0.9 percent) (p=0.032 for 15 mg) and in males (3.1 percent (5 mg); 3.2 percent (15 mg); 0.0 percent (placebo)), added to metformin. Ertugliflozin had no adverse impact on bone mineral density at week 26 (95 percent CI). Symptomatic urinary tract infections, hypoglycemia and hypovolemia adverse events were similar between treatment groups.
• In the 26-week VERTIS SITA (1197-P) Phase 3 study of 291 patients with an A1C of 8.0 – 10.5 percent inadequately controlled with diet and exercise, patients were randomized to ertugliflozin 5 mg and sitagliptin 100 mg, ertugliflozin 15 mg and sitagliptin 100 mg or placebo. The study met its primary endpoint of improved blood glucose control at 26 weeks with A1C reductions of 1.6 percent (ertugliflozin 5 mg and sitagliptin 100 mg), 1.7 percent (ertugliflozin 15 mg and sitagliptin 100 mg), compared with 0.4 percent in patients taking placebo (p<0.001 for both comparisons). In addition, the study met a key secondary endpoint, with significantly more patients taking ertugliflozin 5 mg or 15 mg in combination with sitagliptin 100 mg achieving the A1C treatment goal of less than 7.0 percent (35.7 percent and 31.3 percent, respectively) compared with placebo (8.3 percent) (p<0.001, for both comparisons based on adjusted odds ratio comparisons).
• The following statistically significant placebo-adjusted reductions were observed for the primary and additional key secondary endpoints:
• A1C: 1.2 percent (ertugliflozin 5 mg and sitagliptin 100 mg) and 1.2 percent (ertugliflozin 15 mg and sitagliptin 100 mg) (p<0.001 for both comparisons);
• FPG: 38.9 mg/dL for 5 mg ertugliflozin and 100 mg sitagliptin, 46.1 mg/dL for 15 mg ertugliflozin and 100 mg sitagliptin) (p<0.001 for both comparisons);
• 2-hour PMG: 62.4 mg/dL for ertugliflozin 5 mg and 100 mg sitagliptin and 69.6 mg/dL for ertugliflozin 15 mg and 100 mg sitagliptin (p<0.001 for both comparisons);
• Body weight: 4.4 lbs (2.0 kg) for ertugliflozin 5 mg and sitagliptin 100 mg and 4.6 lbs (2.1 kg) for ertugliflozin 15 mg and sitagliptin 100 mg (p<0.001 for both comparisons);
• SBP: 4.4 mmHg for ertugliflozin 5 mg and sitagliptin 100 mg (p=0.011) and 6.4 mmHg for ertugliflozin 15 mg and sitagliptin 100 mg (p<0.001).
• Observed reductions in DBP were not significant (p>0.05). The incidence of adverse events was 44.9 percent, 44.8 percent and 42.3 percent in the ertugliflozin 5 mg and sitagliptin 100 mg, ertugliflozin 15 mg and sitagliptin 100 mg, and placebo groups, respectively. A higher incidence of genital mycotic infections in males was observed in patients taking ertugliflozin 5 mg (5.3 percent) and 15 mg (1.9 percent) versus placebo (0.0 percent) and in females (4.9 percent (5 mg); 7.0 percent (15 mg); 5.0 percent (placebo)) (p?0.05 for all comparisons). Incidence rates of urinary tract infections, symptomatic hypoglycemia and hypovolemia were low and not significantly different across groups.
• Marketing applications for ertugliflozin and for two fixed-dose combination products (ertugliflozin and Januvia®, ertugliflozin and metformin) are under review with the FDA and the European Medicines Agency. The Prescription Drug User Fee Act (PDUFA) action date from the FDA is in December 2017 for the three New Drug Applications.

Is general: Yes