Bristol-Myers Squibb: dapagliflozin

Therefore, it was deemed a probable drug-induced liver injury (DILI) case associated with dapagliflozin use.

The primary endpoint was a composite of time to first event of CV death, myocardial infarction (MJ), stroke, and hospitalization for unstable angina.

The pre-specified primary analysis compared all dapagliflozin treatment groups (excluding doses below 2.5 mg) to comparators (placebo and active controls).

These findings were confirmed by FDA's sensitivity analysis on the primary composite endpoint and analyses of secondary endpoints also revealed similar point estimates.

While we cannot conclude that dapagliflozin is associated with excess CV risk based on an analysis of only these two trials, the findings from these two large, adequate, and well-designed tr n a relevant patient population cannot be ignored.

Overall, the observed clinical benefits of dapagliflozin in your current clinical development program may be achieved with other available anti-diabetic therapies.

To address the above deficiencies, you will need to submit additional clinical trial data to increase the patient-years of exposure to dapagliflozin and comparators.

We acknowledge your plans to initiate a CV outcomes trial in the fourth quarter of 2012. We strongly advise you to continue with those plans should data from that trial be necessary for consideration in a resubmission to this complete response.

March 2001, Q&A #16, "The applicant must disclose specific details of the financial interest including the size and nature of the financial interest in question ...