0 or titrated to atorvastatin 40 mg ‡ Baseline units: mg/dL; medians for TG, means for all other values § p<0.05 for difference with atorvastatin
LIPTRUZET 10/20 92 -20%§
[203] -31%§
[120] -21%§
[123] +3%
[50.9] -18%
[155] -27%§
[152]
Atorvastatin 40 mg 92 -7%
[201] -11%
[118] -8%
[120] +1%
[52.1] -6%
[148] -10%
[149]
The Ezetimibe Plus Atorvastatin Versus Atorvastatin Titration in Achieving Lower LDL-C Targets in Hypercholesterolemic Patients (EZ-PATH) study, a multicenter, double-blind, controlled, 6-week study, included 556 patients with an LDL-C level ≥70 mg/dL and ≤160 mg/dL (≥1.8 mmol/L and ≤4.1 mmol/L) and at high risk for coronary heart disease (CHD). All patients received atorvastatin 40 mg for a minimum of 4 weeks prior to randomization. Patients not at the optional NCEP ATP III LDL-C level <70 mg/dL (<1.8 mmol/L) were randomized to receive either coadministered ezetimibe and atorvastatin (equivalent to LIPTRUZET 10/40) or atorvastatin 80 mg for 6 weeks.
The patient population was: 39% female; 81% Caucasian, 11% Black, 6% Multi-racial, 2% Asian; 31 to 80 years of age (mean age 52 years).
LIPTRUZET 10/40 was significantly more effective than doubling the dose of atorvastatin to 80 mg in further reducing total-C, LDL-C, Apo B, TG, and non-HDL-C. Results for HDL-C between the two treatment groups were not significantly different. (See Table 12.) In addition, significantly more patients receiving LIPTRUZET 10/40 attained LDL-C <70 mg/dL (<1.8 mmol/L) compared to those receiving atorvastatin 80 mg, 74% vs. 32%.
Table 12: Response to LIPTRUZET in Patients with Primary Hypercholesterolemia (Mean* % Change from Baseline†) Treatment
(Daily Dose) N Total-C
[Baseline‡] LDL-C
[Baseline‡] Apo B
[Baseline‡] HDL-C
[Baseline‡] TG*
[Baseline‡] Non-HDL-C
[Baseline‡]
* For triglycerides, median % change from baseline † Patients on atorvastatin 20 mg, then switched to LIPTRUZET 10/40 or titrated to atorvastatin 80 mg ‡ Baseline units: mg/dL; medians for TG, means for all other values § p<0.05 for difference with atorvastatin
LIPTRUZET 10/40 277 -17%§
[165] -27%§
[89] -18%§
[101] 0%
[47.7] -12%§
[131] -23%§
[117]
Atorvastatin 80 mg 279 -7%
[165] -11%
[90] -8%
[102] -1%
[46.9] -6%
[136] -9%
[118]
LIPTRUZET 10/20 and 10/40 - Clinical Equivalence to Coadministered Components
LIPTRUZET has been shown to be bioequivalent to coadministration of corresponding doses of its ezetimibe and atorvastatin components with the exception of slightly lower atorvastatin Cmax for the 10/20 and 10/40 mg doses [see Clinical Pharmacology (12.3)], which, in two separate studies, have been shown to be clinically equivalent in LDL-C response after six weeks of treatment to their corresponding coadministered components.
In these two multicenter, double-blind, controlled, crossover studies, patients with primary hypercholesterolemia and low, moderate, or moderately high cardiovascular risk received LIPTRUZET 10/20-mg (Study 1) or 10/40-mg (Study 2) tablets or the corresponding coadministered components once daily for 6 weeks. They then crossed over, after a 6-week washout, to the coadministered components or LIPTRUZET at corresponding doses for an additional 6 weeks. From untreated baseline, mean changes in L |
