1 for both doses) mean changes from baseline in systolic blood pressure relative to placebo were -3.7 mmHg and -5.4 mmHg with INVOKANA 100 mg and 300 mg, respectively.
Table 7: Results from 26-Week Placebo-Controlled Clinical Study with INVOKANA as Monotherapy *
Efficacy Parameter Placebo(N=192) INVOKANA100 mg(N=195) INVOKANA300 mg(N=197)
* Intent-to-treat population using last observation in study prior to glycemic rescue therapy
Least squares mean adjusted for baseline value and stratification factors
p<0.001
HbA1C (%)
Baseline (mean) 7.97 8.06 8.01
Change from baseline (adjusted mean) 0.14 -0.77 -1.03
Difference from placebo (adjusted mean) (95% CI) † -0.91‡(-1.09, -0.73) -1.16‡(-1.34, -0.99)
Percent of Patients Achieving HbA1C < 7% 21 45‡ 62‡
Fasting Plasma Glucose (mg/dL)
Baseline (mean) 166 172 173
Change from baseline (adjusted mean) 8 -27 -35
Difference from placebo (adjusted mean) (95% CI) † -36‡(-42, -29) -43‡(-50, -37)
2-hour Postprandial Glucose (mg/dL)
Baseline (mean) 229 250 254
Change from baseline (adjusted mean) 5 -43 -59
Difference from placebo (adjusted mean) (95% CI) † -48‡(-59.1, -37.0) -64‡(-75.0, -52.9)
Body Weight
Baseline (mean) in kg 87.5 85.9 86.9
% change from baseline (adjusted mean) -0.6 -2.8 -3.9
Difference from placebo (adjusted mean) (95% CI) † -2.2‡(-2.9, -1.6) -3.3‡(-4.0, -2.6)
Intent-to-treat population using last observation in study prior to glycemic rescue therapy
Least squares mean adjusted for baseline value and stratification factors
p<0.001
14.2 Combination TherapyAdd-on Combination Therapy With Metformin
A total of 1284 patients with type 2 diabetes inadequately controlled on metformin monotherapy (greater than or equal to 2,000 mg/day, or at least 1,500 mg/day if higher dose not tolerated) participated in a 26-week, double-blind, placebo- and active-controlled study to eva luate the efficacy and safety of INVOKANA in combination with metformin. The mean age was 55 years, 47% of patients were men, and the mean baseline eGFR was 89 mL/min/1.73 m2. Patients already on the required metformin dose (N=1009) were randomized after completing a 2-week, single-blind, placebo run-in period. Patients taking less than the required metformin dose or patients on metformin in combination with another antihyperglycemic agent (N=275) were switched to metformin monotherapy (at doses described above) for at least 8 weeks before entering the 2-week, single-blind, placebo run-in. After the placebo run-in period, patients were randomized to INVOKANA 100 mg, INVOKANA 300 mg, sitagliptin 100 mg, or placebo, administered once daily as add-on therapy to metformin.
At the end of treatment, INVOKANA 100 mg and 300 mg once daily resulted in a statistically significant improvement in HbA1C (p-value <0.001 for both doses) compared to placebo when added to metformin. INVOKANA 100 mg and 300 mg once daily also resulted in a greater proportion of patients achieving an HbA1C less than 7%, in significant reduction in fasting plasma glucose (FPG), in improved postprandial glucose (PPG), and in percent body weight reduction compared to placebo when added to metformin (see Table 8). Statistically significant (p<0.001 for both doses) mean changes from baseline i |
