X hits on this document

520 views

0 shares

0 downloads

0 comments

35 / 170

13

adult sub populations as assessed by less than twofold differences in the sum of

14

Saxagliptin and active metabolite exposures including by age, gender, weight, hepatic

15

impairment or mild renal impairment. Higher Saxagliptin and active metabolite

16

exposures were noted in patients with moderate or severe renal impairment and end stage

17

renal disease. These patients will be managed with a dose adjustment to one half of the

18

usual clinical dose, that is, to 2.5 mgs once daily.

6

In the clinical pharmacology program Saxagliptin given once daily was

7

generally safe and well tolerated at doses up to 400 mgs for two weeks. That is 80x the

20

pharmacokinetic drug-drug interactions with a number of commonly used oral

21

antidiabetic agents as well as other agents commonly used in this patient population

22

including a Statin, gastric acid controllers, and Digoxin. Drug-drug interactions with

23

strong CYP3A inhibitors or induces are minimized because changes in parent drug

24

exposures were offset by opposite changes in active metabolite exposures.

19

In a series of drug-drug interaction studies we found low potential for

Scribes, LLC Toll Free 1-800-675-8846 www.scribesllc.com

1

of a wide range of Saxagliptin doses from 1 to 400 mgs once daily. This enabled

2

robust conclusions regarding dose selection as well as safety experience at doses in great

3

excess of our proposed usual clinical dose. The program included over 670 subjects in

4

clinical pharmacology studies, 423 patients in a phase 2b dose ranging study and over

5

4,200 patients with type 2 diabetes in phase 3 clinical trials.

8

proposed usual clinical dose of 5 mgs. There were no signals for QT prolongation or

9

heart rate changes seen in a thorough QTC study. We observed no safety signals for

10

hypoglycemia, localized edema or skin lesions. In addition, we saw no hepatics, striated

11

muscle, and renal safety signals in laboratory blood tests.

34

12

We observed no clinically meaningful pharmacokinetic differences in

Document info
Document views520
Page views520
Page last viewedFri Dec 09 16:10:45 UTC 2016
Pages170
Paragraphs7975
Words54271

Comments