DSI: Joseph Saponaro

Lipitor/Torcetrapib

A Phase 3, Double-Blind, Placebo-Controlled, Randomized, Parallel Group, Multicenter Study of the Efficacy, Safety, and Tolerability of Fixed Combination Torcetrapib/Atorvastatin Administered Orally, Once Daily for 6 Months, Compared to Atorvastatin Alone or Placebo, in Subjects With Mixed Dyslipidemia (Frederickson Types IIA and IIb).

Sponsor: Pfizer
Study Drug:
Atorvastatin +/- Torcetrapib (CP-529,414)
Protocol: A5091018
Site #: 1037
Investigator #: 1022
CRO = CTMS = Clinical Trial Management Services, inc.
SAE Hotline: 877-812-6905
CRA: Diana B. Long, RN, BSN, CCRA Diana_Long@Groton.Pfizer.com
IVRS (online): IMPALA Central Lab: MDS Pharma Services
Central EKG: Covance
Phase 3 WIRB = Western IRB Optional Pharmacogenomic blood-test
3816 Subjects/120 Sites = 32 Subjects per Site
1908 Subjects in each of: Type IIa (TG < 150) Stratum & 1908 Type IIb (TG ? 150 and ? 500) Stratum
Subjects in each stratum further R into 9 treatment arms (212 x 9 = 1908): Lipitor 10, 20, 40 or 80; Lipitor 10, 20, 40 or 80 Plus Torcetrapib; or Placebo
CETP = Cholesterol Ester Transfer Protein
NCEP ATP III TLC: counsel diet q V. Implement lifestyle changes start & maintain consistent diet & exercise pattern throughout study www.NHLBI.NIH.gov/Guidelines/Cholesterol/
Tourniquet no longer than 2 min. & must be released prior to blood draw
Window: +/- 7 days for scheduled visits, except: VQ3 +/-3 days & VQ2 which will occur 4 to 5 wks after VS1
Perform 3 BPs -> Discard 1st; only 2nd & 3rd count! Use Non-Dominant Arm for all BP measurements!
Note: if BP cuff too small -> BP will be falsely elevated Arm should be bare & supported at heart level
On CRF -> spell out generic names of both meds in combo pills even though CRF says OK to write Brand Name!

IC
Age: 18 years & older
If > 1 RF -> Perform 10 yr. Framingham Risk Assessment
If 10 yr Risk < 10% -> LDL ? 160 AND < 220
If 10 yr Risk ? 10% and ? 20% -> LDL ? 130 and < 190
Fasting mean TG ? 500

EC
CHD or CHD risk equivalent (50% carotid art. Dz or Symptomatic, PVD, AAA, DM, Q-Waves)
Systemic Steroids, TSH > 2x, LFT’s > 2x, SBP > 140 or DBP > 90 @ V Q3 or T4, CHF Class III or IV, Creatinine > 1.7xULN, Proteinuria, CA x 10 yrs., ALP > 1.5x, CK > 3x

V1 W -7 S1 Screening Period, Lab, ICF, UA, TLC, IMPALA, D/C Lipid Med. (OK to add BP Med)
V2 W -3 Q2 Qualifying Period, Lab, EKG, TLC, IMPALA, (4-5 wks after V1)
V3 W -2 Q3 Qualifying Period, Lab, TLC Contact IMPALA when lab results available+/- 3 days window (Qualifying BP < 140/90 or flunk out!) (Call IMPALA 866-426-0292 & request just in time Study Drug)
V4 M 0 T4 Double Blind Treatment Period, Lab, UA, TLC Randomize PE (Qualifying BP < 140/90 or flunk out!)
V5 M 0.5 T5 Lab, TLC, Look for 15 mm rise in BP, +/- 7 days
V6 M 1 T6 Lab, Look for 15 mm rise in BP, TLC +/- 7 days
V7 M 3 T7 Lab, TLC +/- 7 days
V8 M 6 T8 Lab, TLC (also, early termination visit) PE

Framingham Risk Factors (RF) -> If > 1, Perform 10 Yr. Risk Assessment

Smoking
BP 140/90 or Rx'd
HDL < 40 (subtract one RF if > 60)
FH premature CAD in: Men: < 55 or Women < 65
Age: Men: ? 45 or Women ? 55