Anorexia drug study results positive: Par
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BY OUR PHARMA CORRESPONDENT
13th August,2005:The phase II
proof-of-concept clinical trial with concentrated
megestrol acetate oral suspension showed
encouraging results, Par Pharmaceutical Companies,
Inc announced.
In the trial, patients taking concentrated
megestrol acetate 575 mg/5 mL oral suspension
which utilizes NanoCrystal technology gained more
weight, on average, than those taking the older
megestrol acetate oral suspension 800 mg/20 mL.
Although this study was not powered to achieve
statistical significance, there was a substantial
difference in mean weight gain, beginning at day 3
and continuing throughout the trial, with the
concentrated megestrol acetate group gaining 50%
more weight by week 12. In fact, the difference
between the two groups achieved statistical
significance at week 6, the company noted in a
press release.
This randomized, 12 week open-label, study
compared concentrated megestrol acetate 575 mg/5
mL to megestrol acetate 800 mg/20 mL in patients
with HIV infection who had unintentional weight
loss resulting in 10% less than the lower limit of
ideal body weight. Sixty-three patients were
randomized to receive one teaspoon of concentrated
megestrol acetate 575 mg/5 mL or one dosage cup of
megestrol acetate oral suspension 800 mg/20 mL
once daily. Following baseline measurements,
patients were monitored on the primary outcome
measure of weight gain, and several secondary
endpoints, including caloric intake, and appetite
improvement. The study was conducted in South
Africa, India and the United States.
On the primary outcome measure of weight gain,
patients receiving concentrated megestrol acetate
575 mg/5 mL achieved a mean weight gain of 12
pounds (10% of baseline body weight) at the study
endpoint of 12 weeks, compared to an 8 pound
increase (6% of baseline body weight) in weight
for patients receiving megestrol acetate oral
suspension 800 mg/20 mL. Patients administered the
concentrated suspension achieved a similar mean
weight gain of 8 pounds after approximately 6
weeks. The difference between the two groups at
week 6 was statistically significant (p = 0.020).
The rate and nature of significant adverse events
were comparable between the two compounds, and the
other safety information available appears
consistent with the existing package insert.
Further analysis of these study data will be
completed in the coming months.
Par’s recently approved Megace ES (megestrol
acetate) 625 mg/ 5 mL concentrated oral suspension
was not the dosage strength tested in this study.
The company evaluated seven doses of concentrated
megestrol acetate, including a 575 mg/5 mL and a
625 mg/5 mL dose. This study of the 575 mg/5 mL
dose of concentrated megestrol acetate was
initiated prior to the determination that the 625
mg/5 mL dosage strength would be the marketed
dose.
Studies have shown that the pharmacokinetic
characteristics of megestrol acetate are linear
across a broad dose range, therefore the exposure
following administration of 575 mg/5 mL is only
slightly less than the exposure following
administration of 625 mg/5 mL (the marketed dose).
Despite the slightly decreased exposure relative
to the 625 mg/5 mL formulation, the weight gain
achieved following administration of concentrated
megestrol acetate 575 mg/5 mL was greater than
megestrol acetate 800 mg/20 mL, and this
difference was apparent early in treatment. The
safety was similar between the two formulations.
Megace ES and megestrol acetate oral suspension
are indicated for the treatment of anorexia,
cachexia, or an unexplained, significant weight
loss in patients with a diagnosis of acquired
immunodeficiency syndrome (AIDS).
Megace ES and megestrol acetate oral suspension
are contraindicated in patients with a history of
hypersensitivity to megestrol acetate or any
component of the formulation, or patients with
known or suspected pregnancy.
Evidence of adrenal suppression has been observed
in patients receiving megestrol acetate oral
suspension. The glucocorticoid activity of
megestrol acetate oral suspension has not been
fully evaluated.
Clinical cases of new onset diabetes mellitus,
exacerbation of pre-existing diabetes mellitus,
and overt Cushing's Syndrome have been reported in
association with the chronic use of megestrol
acetate.
The most common adverse events (>1% and > than
placebo) associated with Megace ES 625 mg/5 mL and
megestrol acetate oral suspension 800 mg/20 mL are
impotence, flatulence, rash, hypertension,
insomnia, fever, decreased libido, dyspepsia and
hyperglycemia.
Women who participated in studies (n=10) reported
breakthrough bleeding; however, it is unknown if
these events are drug- or disease-related.
Par Pharmaceutical Companies, Inc. develops,
manufactures and markets generic pharmaceuticals
through its principal subsidiary, Par
Pharmaceutical, Inc. The company also is
developing an additional line of branded
pharmaceutical products for specialty markets, the
first of which is Megace ES. Par currently
manufactures, markets or licenses more than 90
prescription drugs. The trade name Megace was
licensed from Bristol-Myers Squibb Company.
BY OUR PHARMA CORRESPONDENT |
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