ABT335

\[(Week 12 triglycerides minus baseline triglycerides)/baseline triglycerides\] x 100

\[(Week 12 HDL-C minus baseline HDL-C)/baseline HDL-C\] x 100

\[(Week 12 LDL-C minus baseline LDL-C)/baseline LDL-C\] x 100

After receiving total daily caloric intake over 20 hrs as 20 identical small meals, starting at 0600 hrs, subjects took study medications at 0800 hrs. Five hours after the first meal, i.v. 5,5,5-2H3-L-leucine was administered, followed by a primed-constant infusion at 10 mol/kg body weight per hr for 15 hrs during which 14 blood samples were collected. Isotopic enrichment of leucine in apoA1 band excised from polyacrylamide gel was calculated. Assuming steady state apo A-I metabolism, we used a compartment model to fit data, consisting a precursor compartment (Compartment 1), the plasma leucine pool, an intracellular compartment accounting for apoA1 synthesis and lipoprotein assembly (Compartment 2), and compartments to account for dispositional kinetics of the subfractions including a plasma pool compartment (Compartment 3). The apoA1 FCR corresponds to the rate of irreversible loss of leucine pools from Compartment 3.

The apolipoprotein A-I production rate using (5,5,5-2H3-L-leucine) was measured following each of the three study periods i.e following 4 weeks of atorvastatin 10 mg/day, following 8 further weeks of ABT335 135 mg/day added to atorvastatin and following 10 further weeks of ER niacin 2000 mg/day and aspirin 325 mg/day added to atorvastatin+ABT335.

Triglyceride iAUC was measured during an oral fat tolerance test administered after 4 weeks of atorvastatin 10 mg/day , a further 8 weeks of atorvastatin 10mg /day+ABT335 135mg/day and then after a further 10 weeks of atorvastatin 10 mg/day+ABT335 135 mg/day+Niaspan 2000 mg/day. The standardized oral fat load was administered one hour post medication dosing and blood was collected prior to drug dosing, prior to the oral fat load and hourly thereafter for 10 hours (0,1,2,3,4,5,6,7,8,9,10,12 hrs post drug dosing)