1. Role of - Azilsartan - Azilsartan/chlorthalidone

2. Azilsartan
Azilsartan Medoximil (AZL-M) is the prodrug of a potent and selective Angiotensin Receptor blocker (ARB) undergoing development for the treatment of hypertension

3. Azilsartan efficacy: Change From Baseline in 24-h Mean BP at Week 6
SBP*
DBP†
Placebo
AZL-M 40 mg
AZL-M 80 mg
Valsartan 320 mg
Olmesartan 40 mg
Placebo
AZL-M 40 mg
AZL-M 80 mg
Valsartan 320 mg
Olmesartan 40 mg
Change in BP (mm Hg) ‡ ‡ ‡ ‡§ ‡
‡§|| ‡¶
‡§||
Baseline: mm Hg
Baseline: mm Hg
*Primary endpoint
†Secondary endpoint
‡P<0.001 vs placebo
§P≤0.001 vs valsartan 320 mg
||P≤0.011 vs olmesartan 40 mg
¶P=0.020 vs valsartan 320 mg
White WB, et al. Hypertension. 2011;57(3):413-20

4. Azilsartan efficacy: Change From Baseline in Clinic BP at Week 6
SBP*
DBP†
Placebo
AZL-M 40 mg
AZL-M 80 mg
Valsartan 320 mg
Olmesartan 40 mg
Placebo
AZL-M 40 mg
AZL-M 80 mg
Valsartan 320 mg
Olmesartan 40 mg
Change in BP (mm Hg) ‡ ‡ ‡ ‡ ‡¶
‡§||
‡§||
‡§||
Baseline: mm Hg
Baseline: mm Hg
*Key secondary endpoint
† Secondary endpoint
‡P<0.001 vs placebo
§P<0.020 vs olmesartan 40 mg
||P<0.001 vs valsartan 320 mg
¶P=0.017 vs valsartan 320 mg
White WB, et al. Hypertension. 2011;57(3):413-20

5. Azilsartan: Change in Trough Sitting Clinic SBP*
Week 6
Week 10
-35.1
-29.5
-37.8
-32.8
-40
-30
-20
-10
AZL-M/CLD
AZL-M+HCTZ
For the primary efficacy endpoint of trough sitting clinic SBP, N=295 for AZL-M--CLD and N=292 for AZL-M + HCTZ at baseline, week 6, and week 10. (Source: Final TLGs dated 29-Mar-2010, Table Analysis of Trough Sitting Clinic SBP (mm Hg) by Study Visit, LOCF, FAS, pages 1, 4, and 6 of 6.)
(FYI: For the study overall, subjects randomized were N=303 for AZL-M--CLD and N=306 for AZL-M + HCTZ, but 1 and 3 subjects, respectively, were randomized but not treated. Therefore, total randomized and treated were N=302 for AZL-M--CLD and N=303 for AZL-M + HCTZ; however, not all of these subjects had the required baseline value and post baseline value. Therefore, final analyzed were N=295 and N=292.)
trough sitting clinic blood pressure: the blood pressure reading taken clinically at the point in time when drug concentrations are lowest, ie. the clinic BP measurements are taken approximately 24 hours after the previous dose and prior to dosing or blood collection on day of clinic visit † †
Baseline values were 164.70.55 mm Hg and 164.40.56 mm Hg
Data are least-squares mean±SE
*Primary endpoint
†P<0.001
Bakris et al. Results of a double-blind randomized study comparing CLD and HCTZ combined with the new ARB Azilsartan Medoxomil in primary HTN. Late breaking Clinical Trial session presented at: American Society of Hypertension Annual Scientific Meeting and Exposition; 2010 May 1-4; NYC, NY
January 26, 2009 5

6. Sustained efficacy at each hour over 24 hours in a 6-week study Azilsartan-M vs Olmesartan-M and Valsartan
White et al. The New Angiotensin Receptor Blocker Azilsartan Medoxomil Has Superior 24-Hour Blood Pressure-Lowering Efficacy to Both Olmesartan and Valsartan. Poster session presented at: American Society of Hypertension Annual Scientific Meeting and Exposition; 2010 May 1-4; NYC,NY

7. Change in SBP by ABPM CLD vs. HCTZ on background of AZL-M
Change in Mean 24-Hour SBP (mmHg) by ABPM
-25.7a
-19.9
-26.6a
-22.4
-30
-20
-10
Week 6
Week 10
AZL-M–CLD
AZL-M + HCTZ
a P<0.001
Baseline
146.5±
0.89
145.4±
0.88
Axis – mmHg by ABPM
Source: Final TLGs dated 29-Mar-2010, Table Analysis of ABPM SBP Measurements (mm Hg) by Study Visit, LOCF, FAS, pages 1, 4, and 6 of 11.
For the primary efficacy endpoint of trough sitting clinic SBP, N=295 for AZL-M--CLD and N=292 for AZL-M + HCTZ at baseline, week 6, and week 10. (Source: Final TLGs dated 29-Mar-2010, Table Analysis of Trough Sitting Clinic SBP (mm Hg) by Study Visit, LOCF, FAS, pages 1, 4, and 6 of 6.)
(FYI: For the study overall, subjects randomized were N=303 for AZL-M--CLD and N=306 for AZL-M + HCTZ, but 1 and 3 subjects, respectively, were randomized but not treated. Therefore, total randomized and treated were N=302 for AZL-M--CLD and N=303 for AZL-M + HCTZ; however, not all of these subjects had the required baseline value and post baseline value. Therefore, final analyzed were N=295 and N=292.)
Data are least-squares mean ± SE.
Bakris et al. Results of a double-blind randomized study comparing CLD and HCTZ combined with the new ARB Azilsartan Medoxomil in primary HTN. Late breaking Clinical Trial session presented at:: American Society of Hypertension Annual Scientific Meeting and Exposition; 2010 May 1-4; NYC,NY
January 26, 2009 7