Abstract
Background
Fenofibrate is used to treat primary hypercholesterolemia, mixed lipidemia, and hypertriglyceridemia
in adults who do not respond to nonpharmacologic measures. Fenofibrate is a prodrug
that is rapidly and completely hydrolyzed to fenofibric acid, the active moiety. A
new orally administered agent, fenofibric acid, was developed as an alternative to
fenofibrate.
Objective
Two separate studies were conducted to evaluate the bioequivalence of fenofibric acid
relative to fenofibrate under fasted and fed (standard breakfast) conditions, characterize
the pharmacokinetic profile, and assess the safety and tolerability of fenofibric
acid.
Methods
In study 1 (fasted), during each study period, volunteers received a single 105-mg
dose of fenofibric acid or single 145-mg dose of fenofibrate (depending on their randomization
scheme) after an overnight fast (a minimum fast of 10 hours). A 7-day washout period
followed the first treatment period, after which the volunteers received the alternate
treatment. Study 2 followed a similar dosing scheme and differed only in that volunteers
received their single dose after being fed a standard meal (575 calories, of which
36% were contributed by fat). Serial blood samples in both studies were collected
up to 72 hours after drug administration. The pharmacokinetic parameters of interest
for assessing bioequivalence were AUC0–t, AUC0–∞, Cmax, and Tmax. The criterion for a lack of difference between products was a 90% CI between 0.80
and 1.25 for the fenofibric acid:fenofibrate ratios for AUC0–t, AUC0–∞, and Cmax. Tolerability was assessed by adverse events (AEs), laboratory parameters, vital signs,
and physical examinations.
Results
Volunteers in study 1 (fasted; n = 54) were aged 18 to 43 years; 19 (35%) were men
and 35 (65%) were women; mean weight was 155.2 pounds (range, 103.0–267.0 pounds);
and 48 (89%) were white, 1 (2%) was black, and 5 (9%) were white/American Indian/Alaskan
native/Asian. Volunteers in study 2 (fed; n = 54) were aged 18 to 43 years; 27 (50%)
were men and 27 (50%) were women; mean weight was 161.9 pounds (range, 112.0–225.0
pounds); and 51 (94%) were white (including 2 Hispanic) and 3 (6%) were black. The
90% CIs about the ratio of the fenofibric acid geometric mean to the fenofibrate geometric
mean were within the 80% and 125% limits for the pharmacokinetic parameters Cmax, AUC0–t, and AUC0–∞ of the ln-transformed data in both study 1 (fasted) and study 2. In study 1 (fasted),
14 volunteers (26%) experienced a total of 29 AEs; the most common nonlaboratory AEs
were dizziness (6%) and headache (4%). In study 2, 12 volunteers (22%) experienced
a total of 19 AEs; the most common nonlaboratory AEs were headache (17%) and dry throat
(4%). AEs were generally mild or moderate in intensity.
Conclusions
In these 2 single-dose studies, these healthy volunteers administered a single oral
dose of 105-mg fenofibric acid met the US Food and Drug Administration regulatory
criteria for assuming bioequivalence to a single oral dose of 145-mg fenofibrate tablets
with respect to the rate and extent of fenofibric acid absorption in both fed and
fasted states. Fenofibric acid at the dose studied was well tolerated in this population.
ClinicalTrials.gov identifiers: NCT00961116 and NCT00960687.
Key words
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Article info
Publication history
Accepted:
May 6,
2011
Identification
Copyright
© 2011 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
