mixed or combined dyslipidemia is described by elevated levels of triglycerides ( tg ) and reduced high - density lipoprotein cholesterol ( hdl - c ) , with or without elevated levels of low - density lipoprotein cholesterol ( ldl - c ) . mixed dyslipidemia is typically linked with an increase of small , dense ldl particles , and an elevated apolipoprotein b. all these changes predispose to an increased risk of cardiovascular disease . mixed dyslipidemia is the most frequent lipid disorder found in patients with type 2 diabetes . initial treatment options for mixed dyslipidemia include lifestyle modification and statin therapy . nevertheless , statin monotherapy is often insufficient to normalize multiple lipid parameters . the hdl - c and tg levels are strong predictor of cardiovascular risk even in patients treated with a statin and has achieved an optimum ldl - c levels . the addition of fibrates to statin therapy offers the prospective for overall lipid control in patients with mixed dyslipidemia . fenofibrate , which belongs to the class of fibrates , has a comparatively low potential for pharmacokinetic interaction as well as lower rates of rhabdomyolysis with statins when compared to gemfibrozil . choline fenofibrate is a newly developed choline salt of fenofibric acid and is more hydrophilic than fenofibrate . it does not require first pass hepatic metabolism to become active , as it dissociates to free fenofibric acid within the gastrointestinal tract and rapidly absorbed throughout the gastrointestinal tract . of the various fenofibrate formulations available , choline fenofibrate is the only formulation of fenofibrate which is approved by the us fda for co - administration with statins . however , there is no indian data available for efficacy and safety of choline fenofibrate in patients of mixed dyslipidemia . hence , this study was planned to evaluate the efficacy and safety of choline fenofibrate in comparison to micronized fenofibrate among indian patients of mixed dyslipidemia stabilized on statin therapy . patients with mixed dyslipidemia of either gender , aged 1870 years having serum tg levels between 150 and 500 mg / dl who were prescribed statin in stable dose for the preceding 8 weeks were enrolled in the study . the primary exclusion criteria included patients with serum ldl - c > 160 mg / dl ; type 1 diabetes mellitus , thyroid dysfunction , active liver disease , patients with renal dysfunction ( serum creatinine more than 1.5 times upper normal limit ) . the study was conducted according to the protocol and in accordance with the ethical guidelines by indian council of medical research . the study was conducted at each trial site after receiving approvals from respective institutional / independent ethics committee and drug controller general of india . the study design was multicenter , open - label , randomized , active controlled , comparative , and parallel group . patients meeting eligibility criteria were enrolled in the study and randomized in 1:1 ratio to receive either choline fenofibrate delayed release 135 mg or micronized fenofibrate 160 mg as per computer generated randomization sheet . there were total six study visits : screening visit ( day  70 ) , enrollment visit ( day 1 ) , follow - up visit 1 ( day 15 ) , follow - up visit 2 ( day 29 ) , follow - up visit 3 ( day 57 ) , and end of study visit ( day 85 ) . enrolled patients were provided allocated study medications for 3 months , and they were evaluated during the study period at the end of 2 weeks , 4 weeks , 8 weeks , and 12 weeks for safety and efficacy evaluation . lipid profile and creatinine phosphokinase ( cpk ) were repeated at the end of 4 weeks , 8 weeks , and 12 weeks . laboratory investigations , performed at the time of screening were repeated at the end of the study . the primary endpoint was percentage change in serum tg levels at the end of treatment ( 12 weeks ) from baseline between two arms . the secondary efficacy endpoint was percentage change in serum hdl - c levels at the end of treatment from baseline . the following safety parameters were also evaluated : any adverse events that were reported voluntarily observed and enquired during the study ; any clinically significant change in the value of laboratory results , vital signs , and physical examination during the study compared to baseline . considering the standard deviation of 78 with a power of 80% , approximately 100 patients per group were required to detect a difference of around 31 . considering 12 weeks duration of study and dropout rate , it was planned to enroll 240 patients at the beginning of the study to have data of 200 evaluable patients . evaluation of efficacy and safety was done on the intention to treat population , which consisted of all randomized patients who completed at least one follow - up visit as per protocol . mean percent change in tg and hdl - c levels at the end of treatment from baseline was statistically evaluated within the group and between the groups by student 's t - test . within group and between - group comparisons for laboratory results were analyzed using  test or fisher 's exact test . patients with mixed dyslipidemia of either gender , aged 1870 years having serum tg levels between 150 and 500 mg / dl who were prescribed statin in stable dose for the preceding 8 weeks were enrolled in the study . the primary exclusion criteria included patients with serum ldl - c > 160 mg / dl ; type 1 diabetes mellitus , thyroid dysfunction , active liver disease , patients with renal dysfunction ( serum creatinine more than 1.5 times upper normal limit ) . the study was conducted according to the protocol and in accordance with the ethical guidelines by indian council of medical research . the study was conducted at each trial site after receiving approvals from respective institutional / independent ethics committee and drug controller general of india . the study design was multicenter , open - label , randomized , active controlled , comparative , and parallel group . patients meeting eligibility criteria were enrolled in the study and randomized in 1:1 ratio to receive either choline fenofibrate delayed release 135 mg or micronized fenofibrate 160 mg as per computer generated randomization sheet . there were total six study visits : screening visit ( day  70 ) , enrollment visit ( day 1 ) , follow - up visit 1 ( day 15 ) , follow - up visit 2 ( day 29 ) , follow - up visit 3 ( day 57 ) , and end of study visit ( day 85 ) . enrolled patients were provided allocated study medications for 3 months , and they were evaluated during the study period at the end of 2 weeks , 4 weeks , 8 weeks , and 12 weeks for safety and efficacy evaluation . lipid profile and creatinine phosphokinase ( cpk ) were repeated at the end of 4 weeks , 8 weeks , and 12 weeks . laboratory investigations , performed at the time of screening were repeated at the end of the study . the primary endpoint was percentage change in serum tg levels at the end of treatment ( 12 weeks ) from baseline between two arms . the secondary efficacy endpoint was percentage change in serum hdl - c levels at the end of treatment from baseline . the following safety parameters were also evaluated : any adverse events that were reported voluntarily observed and enquired during the study ; any clinically significant change in the value of laboratory results , vital signs , and physical examination during the study compared to baseline . considering the standard deviation of 78 with a power of 80% , approximately 100 patients per group were required to detect a difference of around 31 . considering 12 weeks duration of study and dropout rate , it was planned to enroll 240 patients at the beginning of the study to have data of 200 evaluable patients . evaluation of efficacy and safety was done on the intention to treat population , which consisted of all randomized patients who completed at least one follow - up visit as per protocol . mean percent change in tg and hdl - c levels at the end of treatment from baseline was statistically evaluated within the group and between the groups by student 's t - test . within group and between - group comparisons for laboratory results were analyzed using  test or fisher 's exact test . a total of 420 patients were screened across all the sites . of these 226 patients were enrolled in the study - 116 patients were administered choline fenofibrate 135 mg , and 110 were administered micronized fenofibrate 160 mg . of these 226 enrolled patients , 201 patients who completed at least 1 month follow - up were included for intention to treat principle analysis ( 105 patients in choline fenofibrate group and 96 patients in micronized fenofibrate group ) . number of patients lost to follow - up immediately after randomization and not completed even the second follow - up visit on day 28 was 25 . one patient did not take the medication regularly as per protocol , and hence data were not used for analysis . patients from both groups had matching baseline characteristics in terms of age , gender , weight , and body mass index [ table 1 ] . baseline characteristics there was a significant reduction in serum tg levels at the end of 12 weeks study period in both groups with respect to baseline value . serum tg level was reduced by approximately 34.24% in choline fenofibrate group as compared to 38.13% reduction in micronized fenofibrate group at the end of 12 weeks . however , the difference between the group was not statistically significant ( p = 0.471 ) . with both investigational products , this reduction was sustained or increased at the end of 12 weeks in both treatment groups [ figure 1 ] . change in serum triglyceride level in both study groups there was a significant increase in serum hdl - c levels at the end of 4 weeks in both the groups as compared to their baseline values . serum hdl - c level was increased by approximately 10% in choline fenofibrate group as compared to 9% increase in micronized fenofibrate group at the end of 4 weeks . however , the difference between the group was not statistically significant ( p = 0.598 ) [ figure 2 ] . increase in serum hdl - c level was faster in choline fenofibrate group as compared to slower increase in micronized fenofibrate group . the increase in serum hdl - c level was maintained until the end of the study period [ figure 2 ] . significant reduction in total cholesterol and vldl - c from baseline was also observed in both the groups [ table 2 ] . change in serum high - density lipoprotein cholesterol levels in both study groups change in other lipid parameters from baseline choline fenofibrate , as well as micronized fenofibrate , were well tolerated . most commonly reported adverse events during the conduct of study were constipation and headache [ table 3 ] . one patient in micronized fenofibrate group developed leg pain and slight elevation of cpk levels . considering the safety of the subject , further treatment was discontinued , and the adverse event was resolved . no serious or life - threatening adverse event reported during the conduct of the study . none of the patients had liver enzymes elevation 3 times of upper limit of normal ( uln ) . elevation of cpk ( 10 times uln ) was not reported in any of the patients . patients from both groups had matching baseline characteristics in terms of age , gender , weight , and body mass index [ table 1 ] . there was a significant reduction in serum tg levels at the end of 12 weeks study period in both groups with respect to baseline value . serum tg level was reduced by approximately 34.24% in choline fenofibrate group as compared to 38.13% reduction in micronized fenofibrate group at the end of 12 weeks . however , the difference between the group was not statistically significant ( p = 0.471 ) . with both investigational products , this reduction was sustained or increased at the end of 12 weeks in both treatment groups [ figure 1 ] . there was a significant increase in serum hdl - c levels at the end of 4 weeks in both the groups as compared to their baseline values . serum hdl - c level was increased by approximately 10% in choline fenofibrate group as compared to 9% increase in micronized fenofibrate group at the end of 4 weeks . however , the difference between the group was not statistically significant ( p = 0.598 ) [ figure 2 ] . increase in serum hdl - c level was faster in choline fenofibrate group as compared to slower increase in micronized fenofibrate group . the increase in serum hdl - c level was maintained until the end of the study period [ figure 2 ] . significant reduction in total cholesterol and vldl - c from baseline was also observed in both the groups [ table 2 ] . change in serum high - density lipoprotein cholesterol levels in both study groups change in other lipid parameters from baseline most commonly reported adverse events during the conduct of study were constipation and headache [ table 3 ] . one patient in micronized fenofibrate group developed leg pain and slight elevation of cpk levels . considering the safety of the subject , further treatment was discontinued , and the adverse event was resolved . no serious or life - threatening adverse event reported during the conduct of the study . none of the patients had liver enzymes elevation 3 times of upper limit of normal ( uln ) . elevation of cpk ( 10 times uln ) was not reported in any of the patients . high serum tg , low hdl - c levels , and often nonoptimal serum ldl - c levels are the hallmarks of mixed dyslipidemia . the presence of high tg and low hdl - c levels are independently associated with increased coronary heart disease risk . when compared with elevated ldl - c alone , the combination of high tg and/or low hdl - c in addition to suboptimal ldl - c poses a significantly higher risk for cardiovascular events . fenofibrate is a prodrug and undergoes rapid hydrolysis at the ester bond to form fenofibric acid , which is the active metabolite . fenofibrate is a neutral , lipophilic compound and is practically insoluble in water ; which makes it difficult to consistently attain therapeutic levels . initially , micronized formulations that increased solubility by reducing particle size , and increasing surface area were introduced . a formulation of the active metabolite ( fenofibric acid ) with a choline salt form was developed resulting in a hydrophilic compound with the greatest bioavailability of the available formulations . the results of our study indicated that there was a significant reduction in the serum tg levels observed with 12 weeks treatment of fenofibrate ( 34.24% in choline fenofibrate group vs. 38.13% in micronized fenofibrate group ) . there was also a significant increase in the serum hdl - c levels observed with 12 weeks treatment of fenofibrate ( 8.6% in choline fenofibrate group vs. 10.56% in micronized fenofibrate group ) . results of our study were similar to the pooled subgroup analysis of three randomized controlled phase iii clinical trials of choline fenofibrate was . in the pooled analysis , the addition of fibrates to moderate dose of statin yielded approximately 43% reduction in serum tg levels and 16% increase in hdl - c levels over a period of 12 weeks . for patients with type 2 diabetes , statin monotherapy however , statin alone often does not normalize other lipid parameters in patients having mixed dyslipidemia . recent retrospective analyses showed that in majority of patients with mixed dyslipidemia on statin monotherapy have suboptimal serum levels of ldl - c , hdl - c , and tg . in type 2 diabetes patients with dyslipidemia , a considerable residual risk persists even after statin therapy . in patients not achieving the target goals for lipid parameters , one of the options is to increase statin dose , but increasing statin dose increases the risk of side effects like myopathy . in such group of patients with below normal hdl - c and tg levels , other lipid parameters were also improved with use of both the drugs in the patients . serum total cholesterol and very ldl - c levels were also reduced with use of both the drugs during the study period . the result of our clinical study was comparable with previously reported results available in the literature . concomitant use of statins and fibrates is believed to further increase the incidence of myalgia and muscle damage . however , in our study concomitant use of fibrate with statin was found to be safe , and no increased incidence of muscle damage was reported . a meta - analysis which included six clinical trials and 1628 subjects reported no cases of myopathy or muscle damage but showed a significant increase in elevation of liver enzymes in statin - fibrate combination therapy when compared to statin monotherapy . the study concluded that statin - fibrate combination therapy was well tolerated . except in a single case who complained of myalgia in micronized fenofibrate group , all others tolerated it very well . in none of the patients , clinically significant elevation of liver enzymes or cpk overall , results of the current study concluded that 135 mg of choline fenofibrate is as safe and effective as 160 mg of micronized fenofibrate in indian patients with mixed dyslipidemia . both study drugs , i.e. , choline fenofibrate and micronized fenofibrate were well tolerated and resulted in more comprehensive improvement in the abnormal lipid profile .
introduction : choline fenofibrate is a newly developed choline salt of fenofibric acid , which is more hydrophilic than fenofibrate . 
 this study was initiated to evaluate the safety and efficacy of choline fenofibrate in comparison to micronized fenofibrate among indian patients of mixed dyslipidemia.methods:a multicenter , open - label , randomized , active controlled , comparative , parallel group study was conducted at around 10 centers spread all across the country . 
 mixed dyslipidemia patients ( serum triglycerides [ tg ] levels between 150 and 500 mg / dl ) , aged 1870 years and taking stable statin dose for 8 weeks were randomized to choline fenofibrate 135 mg delayed release tablets and micronized fenofibrate 160 mg tablets once daily for 12 weeks . 
 the primary endpoint of the study was percentage change in serum tg level at the end of 12 weeks.results:a total of 226 patients were enrolled in this study , of which 116 patients were administered choline fenofibrate and 110 patients were administered micronized fenofibrate . at the end of 12 weeks , there was a significant reduction in tg level ( 34.24% in choline fenofibrate group and 38.13% reduction in micronized fenofibrate group ) . 
 however , the difference between group was not statistically different ( p = 0.471 ) . similarly , there was a significant increase in high - density lipoprotein cholesterol at the end of 12 weeks ( 10% increase in choline fenofibrate group and 9% increase in micronized fenofibrate group ) ; but the difference between the group was not statistically significant ( p = 0.598 ) . 
 both the treatment was safe and well tolerated.conclusion:choline fenofibrate delayed release 135 mg is as safe and effective as 160 mg of micronized fenofibrate in indian patients with mixed dyslipidemia .