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Efficacy and tolerability of atorvastatin/fenofibrate fixed-dose combination tablet compared with atorvastatin and fenofibrate monotherapies in patients with dyslipidemia: a 12-week, multicenter, double-blind, randomized, parallel-group study.
Clin Ther 2009; 31(12):2824-38CT

Abstract

BACKGROUND

Coadministration of statin and fenofibrate monotherapies is frequently used to treat patients with dyslipidemia; however, a fixed-dose combination (FDC) tablet is not currently marketed.

OBJECTIVE

This study evaluates a new FDC tablet of atorvastatin 40 mg and fenofibrate 100 mg.

METHODS

This was a 12-week, multicenter, double-blind, randomized, parallel-group Phase IIb study. Adults with dyslipidemia (non-HDL-C >130 mg/dL and triglycerides [TG] > or =150 but < or =500 mg/dL) were randomly assigned in a 1:1:1 ratio to receive the FDC, atorvastatin 40 mg, or fenofibrate 145 mg for 12 weeks. Study medication was taken once daily in the evening, without regard to meals. Patients attended follow-up visits after 4, 8, and 12 weeks of the double-blind treatment. The primary efficacy end points were the mean percentage changes from baseline to the final visit (week 12) in non-HDL-C, HDL-C, and TG. Secondary variables were LDL-C, VLDL-C particle concentration, total cholesterol, apolipoprotein B, lipoprotein (a), high-sensitivity C-reactive protein, fibrinogen, homocysteine, creatinine, myeloperoxidase, and lipoprotein-associated phospholipase A2. Tolerability was assessed by adverse events, laboratory parameters, vital signs, physical examinations, and ECGs.

RESULTS

Patients (n = 220) were aged 26 to 87 years; 115 (52.3%) were men and 105 (47.7%) were women; 189 (85.9%) were white, 17 (7.7%) were black, and 15 (6.8%) were Hispanic or Latino; and mean (SD) weight was 200.5 (40.85) lb (range, 103.5-367.4 lb). Previous treatments were statins (25.9% [57/220]), fibrates (1.8% [4/220]), and dietary supplements (25.5% [56/220]); 57.7% (127/220) of patients were treatment naive. Use of the FDC was associated with an improvement in non-HDL-C (-44.8%) that was significantly greater than with fenofibrate monotherapy (-16.1%; P < 0.001) but was not significantly different from that with atorvastatin monotherapy (-40.2%; P = NS). HDL-C increased significantly more in the FDC group (19.7%) than with atorvastatin (6.5%; P < 0.001) but was not significantly different from fenofibrate (18.2%; P = NS). TG lowering in the FDC group (-49.1%) was significantly greater than with both atorvastatin (-28.9%; P < 0.001) and fenofibrate (-27.8%; P = 0.001). LDL-C lowering in the FDC group (-42.3%) was significantly greater than with fenofibrate (-13.9%; P < 0.001) but not significantly different from atorvastatin (-43.1%; P = NS). The FDC had either comparable or significantly greater improvements in other lipid variables and multiple secondary variables. The FDC was generally well tolerated; the tolerability profile was consistent with those of atorvastatin and fenofibrate monotherapies. Treatment-emergent adverse events (ie, those occurring after the first dose of study medication) were recorded in 43 of 73 patients (58.9%) for the FDC, 49 of 74 (66.2%) for atorvastatin, and 48 of 73 (65.8%) for fenofibrate.

CONCLUSIONS

In this 12-week study, patients with dyslipidemia treated with the 40/100-mg atorvastatin/ fenofibrate FDC had a significantly greater reduction in TG than those treated with atorvastatin 40 mg or higher-dose fenofibrate 145 mg. Treatment with the FDC was also associated with a significantly greater reduction in non-HDL-C compared with fenofibrate alone and a greater increase in HDL-C compared with atorvastatin alone. All treatments were generally well tolerated.

Authors+Show Affiliations

The University of Chicago, Pritzker School of Medicine, Chicago, Illinois, USA. michaeldavidson@radiantresearch.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20110022

Citation

Davidson, Michael H., et al. "Efficacy and Tolerability of Atorvastatin/fenofibrate Fixed-dose Combination Tablet Compared With Atorvastatin and Fenofibrate Monotherapies in Patients With Dyslipidemia: a 12-week, Multicenter, Double-blind, Randomized, Parallel-group Study." Clinical Therapeutics, vol. 31, no. 12, 2009, pp. 2824-38.
Davidson MH, Rooney MW, Drucker J, et al. Efficacy and tolerability of atorvastatin/fenofibrate fixed-dose combination tablet compared with atorvastatin and fenofibrate monotherapies in patients with dyslipidemia: a 12-week, multicenter, double-blind, randomized, parallel-group study. Clin Ther. 2009;31(12):2824-38.
Davidson, M. H., Rooney, M. W., Drucker, J., Eugene Griffin, H., Oosman, S., & Beckert, M. (2009). Efficacy and tolerability of atorvastatin/fenofibrate fixed-dose combination tablet compared with atorvastatin and fenofibrate monotherapies in patients with dyslipidemia: a 12-week, multicenter, double-blind, randomized, parallel-group study. Clinical Therapeutics, 31(12), pp. 2824-38. doi:10.1016/j.clinthera.2009.12.007.
Davidson MH, et al. Efficacy and Tolerability of Atorvastatin/fenofibrate Fixed-dose Combination Tablet Compared With Atorvastatin and Fenofibrate Monotherapies in Patients With Dyslipidemia: a 12-week, Multicenter, Double-blind, Randomized, Parallel-group Study. Clin Ther. 2009;31(12):2824-38. PubMed PMID: 20110022.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and tolerability of atorvastatin/fenofibrate fixed-dose combination tablet compared with atorvastatin and fenofibrate monotherapies in patients with dyslipidemia: a 12-week, multicenter, double-blind, randomized, parallel-group study. AU - Davidson,Michael H, AU - Rooney,Michael W, AU - Drucker,Joan, AU - Eugene Griffin,H, AU - Oosman,Sonia, AU - Beckert,Michael, AU - ,, PY - 2009/10/28/accepted PY - 2010/1/30/entrez PY - 2010/1/30/pubmed PY - 2010/4/3/medline SP - 2824 EP - 38 JF - Clinical therapeutics JO - Clin Ther VL - 31 IS - 12 N2 - BACKGROUND: Coadministration of statin and fenofibrate monotherapies is frequently used to treat patients with dyslipidemia; however, a fixed-dose combination (FDC) tablet is not currently marketed. OBJECTIVE: This study evaluates a new FDC tablet of atorvastatin 40 mg and fenofibrate 100 mg. METHODS: This was a 12-week, multicenter, double-blind, randomized, parallel-group Phase IIb study. Adults with dyslipidemia (non-HDL-C >130 mg/dL and triglycerides [TG] > or =150 but < or =500 mg/dL) were randomly assigned in a 1:1:1 ratio to receive the FDC, atorvastatin 40 mg, or fenofibrate 145 mg for 12 weeks. Study medication was taken once daily in the evening, without regard to meals. Patients attended follow-up visits after 4, 8, and 12 weeks of the double-blind treatment. The primary efficacy end points were the mean percentage changes from baseline to the final visit (week 12) in non-HDL-C, HDL-C, and TG. Secondary variables were LDL-C, VLDL-C particle concentration, total cholesterol, apolipoprotein B, lipoprotein (a), high-sensitivity C-reactive protein, fibrinogen, homocysteine, creatinine, myeloperoxidase, and lipoprotein-associated phospholipase A2. Tolerability was assessed by adverse events, laboratory parameters, vital signs, physical examinations, and ECGs. RESULTS: Patients (n = 220) were aged 26 to 87 years; 115 (52.3%) were men and 105 (47.7%) were women; 189 (85.9%) were white, 17 (7.7%) were black, and 15 (6.8%) were Hispanic or Latino; and mean (SD) weight was 200.5 (40.85) lb (range, 103.5-367.4 lb). Previous treatments were statins (25.9% [57/220]), fibrates (1.8% [4/220]), and dietary supplements (25.5% [56/220]); 57.7% (127/220) of patients were treatment naive. Use of the FDC was associated with an improvement in non-HDL-C (-44.8%) that was significantly greater than with fenofibrate monotherapy (-16.1%; P < 0.001) but was not significantly different from that with atorvastatin monotherapy (-40.2%; P = NS). HDL-C increased significantly more in the FDC group (19.7%) than with atorvastatin (6.5%; P < 0.001) but was not significantly different from fenofibrate (18.2%; P = NS). TG lowering in the FDC group (-49.1%) was significantly greater than with both atorvastatin (-28.9%; P < 0.001) and fenofibrate (-27.8%; P = 0.001). LDL-C lowering in the FDC group (-42.3%) was significantly greater than with fenofibrate (-13.9%; P < 0.001) but not significantly different from atorvastatin (-43.1%; P = NS). The FDC had either comparable or significantly greater improvements in other lipid variables and multiple secondary variables. The FDC was generally well tolerated; the tolerability profile was consistent with those of atorvastatin and fenofibrate monotherapies. Treatment-emergent adverse events (ie, those occurring after the first dose of study medication) were recorded in 43 of 73 patients (58.9%) for the FDC, 49 of 74 (66.2%) for atorvastatin, and 48 of 73 (65.8%) for fenofibrate. CONCLUSIONS: In this 12-week study, patients with dyslipidemia treated with the 40/100-mg atorvastatin/ fenofibrate FDC had a significantly greater reduction in TG than those treated with atorvastatin 40 mg or higher-dose fenofibrate 145 mg. Treatment with the FDC was also associated with a significantly greater reduction in non-HDL-C compared with fenofibrate alone and a greater increase in HDL-C compared with atorvastatin alone. All treatments were generally well tolerated. SN - 1879-114X UR - https://www.unboundmedicine.com/medline/citation/20110022/Efficacy_and_tolerability_of_atorvastatin/fenofibrate_fixed_dose_combination_tablet_compared_with_atorvastatin_and_fenofibrate_monotherapies_in_patients_with_dyslipidemia:_a_12_week_multicenter_double_blind_randomized_parallel_group_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(09)00469-X DB - PRIME DP - Unbound Medicine ER -