Steady-state bioavailability of prescription omega-3 on a low-fat diet is significantly improved with a free fatty acid formulation compared with an ethyl ester formulation: the ECLIPSE II study

Figures & data

Figure 1 ECLIPSE II study design.

Table 1 Pharmacokinetic parameters calculated for baseline-adjusted total EPA + DHA, total EPA and total DHA following repeated dosing

AUC0-τ	Area under the plasma concentration versus time curve from time 0 to 24 hours postdose
Cmax,ss	Minimum measured plasma concentration
Cmax,ss	Maximum measured plasma concentration
Tmax,ss	Time of the maximum measured plasma concentration
Cavg,ss	Average plasma concentration at steady-state, calculated as AUC0-τ/τ, where τ is the duration of the dosing interval, ie, 24 hours
Flux	Percent peak-to-trough fluctuation at steady-state, calculated as (Cmax,ss−Cmin,ss)/Cavg,ss × 100
Swing	Ratio of the magnitude of change between Cmax,ss and Cmin,ss relative to Cmin,ss at steady-state, calculated as (Cmax,ss−Cmin,ss)/Cmin,ss × 100

Abbreviations: AUC, area under the concentration-time curve; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid.

Table 2 Subject demographics and disposition

Trait	Category/statistic	Epanova cohort	Lovaza cohort	Overall
Sex	Female	5	10	15
	Male	21	16	37
Race	American	0	1	1
	Indian/alaska
	Native
	White	26	25	51
Ethnicity	Hispanic or Latino	23	22	45
	Not Hispanic or Latino	3	4	7
Age (years)	Mean	39.2	34.6	36.9
	Range	19–55	18–51	18–55
Weight (kg)	Mean	75.52	70.97	73.24
	Range	52.4–97.5	57.9–85.6	52.4–97.5
Height (cm)	Mean	168.8	165.1	167.0
	Range	154–186	147–176	147–186
BMI (kg/m^2)	Mean	26.345	26.048	26.197
	Range	21.21–29.68	21.58–29.84	21.21–29.84

Abbreviation: BMI body mass index.

Figure 2 Mean unadjusted plasma total EPA + DHA concentrations.

Abbreviations: EPA, eicosapentaenoic acid; hr, hour; DHA, docosahexaenoic acid.

Figure 3 Mean (SD) baseline-adjusted plasma total EPA + DHA concentrations.

Abbreviations: EPA, eicosapentaenoic acid; SD, standard deviation; DHA, docosahexaenoic acid.

Figure 4 Mean (SD) baseline-adjusted plasma total EPA concentrations.

Abbreviations: EPA, eicosapentaenoic acid; SD, standard deviation.

Figure 5 Mean (SD) baseline-adjusted plasma total DHA concentrations.

Abbreviations: SD, standard deviation; DHA, docosahexaenoic acid.

Figure 6 Mean baseline-adjusted plasma total EPA + DHA − C_avg.ss

Abbreviations: EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid.

Figure 7 Mean baseline-adjusted plasma total EPA + DHA − C_avg,ss.

Abbreviations: EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid.

Table 3 Summary of the baseline-adjusted pharmacokinetic parameters of total EPA + DHA, total EPA and total DHA in plasma

Pharmacokinetic parameter	Epanova™ (n = 25)	Lovaza® (n = 26)
Total EPA + DHA
AUC0-τ (nmol · hr/mL)	19,100 (34.2)	3,320 (75.8)a
Cmax,ss (nmol/mL)	1,350 (29.28)	206.7 (65.28)
Cavg,ss (nmol/mL)	804 (34.2)	138 (75.8)a
Tmax,ss (hr)	6.00 (5.00, 7.00)	6.03 (5.00, 9.00)
Total EPA
AUC0-τ (μg · hr/mL)	4,230 (33.4)	576 (65.7)
Cmax,ss (μg/ml)	295.0 (30.44)	34.22 (66.87)
Cavg,ss (μg/ml)	178 (33.4)	24.0 (65.7)
Tmax,ss (hr)	6.00 (5.00, 8.00)	6.56 (5.00, 9.00)
Total DHA
AUC0-τ (μg · hr/mL)	1,660 (41.0)	537 (60.5)b
Cmax,ss (μg/ml)	124.1 (29.84)	30.56 (68.30)
Cavg,ss (μg/ml)	69.9 (41.0)	22.4 (60.5)b
Tmax,ss (hr)	6.00 (5.00, 9.00)	6.03 (5.00, 12.0)

Notes: AUC_0-τ’ C_max,ss, and C_avg,ss are presented as geometric mean (geometric CV%); T_max,ss is presented as median (minimum, maximum).

a n = 25;

b n = 23.

Abbreviations: AUC, area under the concentration-time curve; AUC_0-τ, area under the plasma concentration versus time curve from time 0 to 24 hours postdose; C_max,ss, maximum measured plasma concentration; T_max,ss, time of the maximum measured plasma concentration; C_max,ss’ average plasma concentration at steady-state, calculated as AUC_0-τ/τ, where τ is the duration of the dosing interval, ie, 24 hours; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; hr, hours.

Table 4 Summary of the statistical comparisons of the pharmacokinetic parameters of baseline-adjusted total EPA + DHA, total EPA, and total DHA in plasma

Pharmacokinetics parameter	Geometric least-squaresmean		% mean ratio	90% CI	P-value
	Epanova™	Lovaza®
Total EPA + DHA
AUC0-τ (nmol · hour/mL)	19,110.87	3,320.07	575.62	447.37–740.64	<0.0001
Cmax,ss (nmol/mL)	1,349.57	206.69	652.93	523.48–814.39	<0.0001
Total EPA
AUC0-τ (μg · hour/mL)	4,225.56	576.12	733.45	584.10–920.99	<0.0001
Cmax,ss (μg/ml)	295.04	34.22	862.28	687.73–1081.14	<0.0001
Total DHA
AUC0-τ(μg · hour/mL)	1,660.19	536.86	309.24	245.01–390.30	<0.0001
Cmax,ss (μg/mL)	124.10	30.56	406.12	323.10–510.48	<0.0001

Abbreviations: AUC, area under the concentration-time curve; CI, confidence interval; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid. AUC_0-τ, area under the plasma concentration versus time curve from time 0 to 24 hours postdose; C_max,ss, maximum measured plasma concentration.

Table 5 Summary of the lipid parameters at baseline (mg/dL) and percent change from baseline after 2 weeks of dosing

Lipid/visit	Epanova™ cohort	Lovaza® cohort	LSM difference	P-value
Triglycerides
Baseline, mean (SD)	185.8 (82.40)	145.3 (75.90)
Percent change, mean (SD)	−22.0 (14.50)	−7.5 (19.26)
LSM (SE)	−21.2 (3.48)	−8.3 (3.41)	−12.9	0.013
HDL cholesterol
Baseline, mean (SD)	41.9 (10.68)	44.4 (10.37)
Percent change, mean (SD)	−4.7 (9.07)	−7.7 (10.15)
LSM (SE)	−5.0 (1.87)	−7.4 (1.84)	2.3	0.382
LDL cholesterol
Baseline, mean (SD)	126.6 (27.03)	130.0 (38.53)
Percent change, mean (SD)	−4.0 (13.16)	0.4 (14.39)
LSM (SE)	−4.0 (2.78)	0.4 (2.73)	−4.5	0.257
Non–HDL cholesterol
Baseline, mean (SD)	146.5 (32.25)	145.2 (42.77)
Percent change, mean (SD)	−4.9 (10.88)	1.3 (14.18)
LSM (SE)	−4.9 (2.56)	1.3 (2.51)	−6.1	0.093

Notes: Epanova cohort, n = 26 at baseline and n = 25 after 2 weeks of dosing; lovaza cohort, n = 26 at baseline and n = 26 after 2 weeks of dosing.

Abbreviations: LSM, geometric least-squares means; SD, standard deviation; SE, standard error; HDL, high-density lipoprotein; LDL, low-density lipoprotein.

Figure 8 Correlation between percent change in triglyceride levels and percent change in unadjusted plasma total EPA + DHA; Epanova and Lovaza cohorts.

Abbreviations: EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; corr, correlation.