DSI: Joseph Saponaro

DiZo Study
Diovan/Zocor

A 10-12 week multicenter, randomized, double blind, parallel group study to evaluate the efficacy and Safety of the combination of Valsartan (Diovan) 320 mgm and Simvastatin (Zocor) 80 mgm compared to Diovan 320 mgm and Zocor 80 mgm monotherapies in essential hypertension and hypercholesterolemia.

Sponsor: Novartis
Study Drug: Diovan +/or Zocor
Protocol: VAS489A2316 Phase 3
Project Manager: Tony Eckhoff: 813-350-8406 (ICON Clinical Research Project Manager) www.ICONClinical.com
Site #: 0517
Heather Campbell, Clinical Trials Safety Operations for SAE reporting
ICON CRA: Norgartc@ICONus.com 847-580-4605
Fax: 847-580-4360
E-Portal: www.ETrials.Novartis.com (Help at: 862-778-8835 or 6)
Central Lab: Clinical Reference Laboratory (CRL) www.CRLcorp.com
Last day to enroll subjects: July 2005
Central IRB = Quorum Review IRB www.QuorumReview.com
330 Subjects/35 Sites = 11 Subjects per Site
110 Subjects in each of three treatment arms: Diovan 320 alone; Zocor 80 alone or the combination of Diovan 320 + Zocor 80 together
Enroll subjects between 7 – 11AM

NCEP ATP III TLC Diet: counsel TLC diet q V. Implement lifestyle changes
Start & maintain consistent diet & exercise pattern throughout study -> www.NHLBI.NIH.gov/Guidelines/Cholesterol/

Optional Exploratory Pharmacogenetic Biomarker component requires a separate signature to test markers of genetic polymorphism on pharmacologic action and/or tolerability. The DNA may be held for 20 years and kept confidential!

IC
Age: 18 - 75
On moderate dose statin > 3 months
V2 SBP ? 135 and < 180
V3 SBP ? 145 and < 180
V4 SBP ? 150 and < 180
TG ? 350
LDL 100 - 190

EC
CHD, CVA, TIA, Trans > 1.5x, renal > 1.5x, CK > 2x, inability to safely d/c all BP & cholesterol meds x 12 wks, insulin, HgbA1C > 7.5, TG > 350 , CA x 5 yrs, inhaled steroids, BCP, Dig, Coumadin, Anti-arrhythmic, SNRI, MAOI, Sudafed, Albuterol, Triptan, NTG

V1 D -42 to -29 Washout Period 1 ICF, TLC, D/C Lipid & BP Meds Assign unique patient number, window +/- 3 days, RTC 14 D
V2 D -28 to -15 SB Run-in Period 2 Lab, UA, EKG, TLC, SBP ? 135 and < 180, CPE, +/- 3 days, RTC 14-28 D
V3 D -14 to -1 Lab, TLC, SBP ? 145 and < 180 & LDL > 100, window +/- 3 days, RTC 1 - 14 D V4a D 0 Apply ABPM (Ambulatory Blood Pressure Monitoring) (urine pregnancy test) V4 D 1 Remove ABPM, Double Blind Treatment Period 3 R Lab, SBP ? 150 and < 180, TLC, Assign Randomization Number, window +/- 3 days Remind subjects they will have blood drawn for Pharmacogenetic Biomarkers this visit
V5 D 15 Lab TLC window +/- 3 days, RTC 14 Days
V6 D 29 Lab TLC window +/- 3 days, RTC 13 Days
V7a D 42 Apply ABPM (Ambulatory Blood Pressure Monitoring)
V7 D 43 Lab, Remove ABPM TLC window +/- 3 days

Moderate to High Doses of Statins defined as at least:

Mevacor (Lovastatin) 40
Zocor (Simvastatin) 20
Pravachol (Pravastatin) 80
Lescol (Fluvastatin) 80
Lipitor (Atorvastatin) 20
Crestor (Rosuvastatin) 10