l impairment (eGFR 30 to less than 60 mL/min/1.73 m2) and age 75 years and older (Table 2) [see Dosage and Administration (2.2) Warnings and Precautions (5.1), and Use in Specific Populations (8.5 and 8.6)].
Table 2: Proportion of Patients With at Least one Volume Depletion-Related Adverse Reactions (Pooled Results from 8 Clinical Trials) Baseline Characteristic Comparator Group *% INVOKANA 100 mg% INVOKANA 300 mg%
* Includes placebo and active-comparator groups
Patients could have more than 1of the listed risk factors
Overall population 1.5% 2.3% 3.4%
75 years of age and older † 2.6% 4.9% 8.7%
eGFR less than 60 mL/min/1.73 m2 † 2.5% 4.7% 8.1%
Use of loop diuretic † 4.7% 3.2% 8.8%
* Includes placebo and active-comparator groups
Patients could have more than 1of the listed risk factors
Overall population 1.5% 2.3% 3.4%
75 years of age and older † 2.6% 4.9% 8.7%
eGFR less than 60 mL/min/1.73 m2 † 2.5% 4.7% 8.1%
Use of loop diuretic † 4.7% 3.2% 8.8%
Impairment in Renal Function
INVOKANA is associated with a dose-dependent increase in serum creatinine and a concomitant fall in estimated GFR (Table 3). Patients with moderate renal impairment at baseline had larger mean changes.
Table 3: Changes in Serum Creatinine and eGFR Associated with INVOKANA in the Pool of Four Placebo-Controlled Trials and Moderate Renal Impairment Trial * Week 26 in mITT LOCF population
PlaceboN=646 INVOKANA 100 mgN=833 INVOKANA 300 mgN=834
Pool of Four Placebo-Controlled Trials Baseline Creatinine (mg/dL) 0.84 0.82 0.82
eGFR (mL/min/1.73 m2) 87.0 88.3 88.8
Week 6 Change Creatinine (mg/dL) 0.01 0.03 0.05
eGFR (mL/min/1.73 m2) -1.6 -3.8 -5.0
End of Treatment Change * Creatinine (mg/dL) 0.01 0.02 0.03
eGFR (mL/min/1.73 m2) -1.6 -2.3 -3.4
PlaceboN=90 INVOKANA 100 mgN=90 INVOKANA 300 mgN=89
Moderate Renal Impairment Trial Baseline Creatinine (mg/dL) 1.61 1.62 1.63
eGFR (mL/min/1.73 m2) 40.1 39.7 38.5
Week 3 Change Creatinine (mg/dL) 0.03 0.18 0.28
eGFR (mL/min/1.73 m2) -0.7 -4.6 -6.2
End of Treatment Change * Creatinine (mg/dL) 0.07 0.16 0.18
eGFR (mL/min/1.73 m2) -1.5 -3.6 -4.0
* Week 26 in mITT LOCF population
In the pool of four placebo-controlled trials where patients had normal or mildly impaired baseline renal function, the proportion of patients who experienced at least one event of significant renal function decline, defined as an eGFR below 80 mL/min/1.73 m2 and 30% lower than baseline, was 2.1% with placebo, 2.0% with INVOKANA 100 mg, and 4.1% with INVOKANA 300 mg. At the end of treatment, 0.5% with placebo, 0.7% with INVOKANA 100 mg, and 1.4% with INVOKANA 300 mg had a significant renal function decline.
In a trial carried out in patients with moderate renal impairment with a baseline eGFR of 30 to less than 50 mL/min/1.73 m2 (mean baseline eGFR 39 mL/min/1.73 m2) [see Clinical Studies (14.3)] , the proportion of patients who experienced at least one event of significant renal function decline, defined as an eGFR 30% lower than baseline, was 6.9% with placebo, 18% with INVOKANA 100 mg, and 22.5% with INVOKANA 300 mg. At the end of treatment, 4.6% with placebo, 3.4% with INVOKANA 100 mg, and 3.4% with INVOKANA 300 mg had a significant renal function decline.
In a pooled population of patients with moderate renal impairment (N=1085) with baseline eGFR of 30 to less than 60 mL/min/1.73 m2 (mean baselin |
