Spring Valley, New York, July 26, 2005 — Par Pharmaceutical Companies, Inc. (NYSE:PRX)
today announced results of a Phase II proof-of-concept clinical trial with concentrated megestrol acetate oral suspension which utilizes NanoCrystal® Technology*. In the trial, patients taking concentrated megestrol acetate 575 mg/5 mL gained more weight, on average, than those taking the older megestrol acetate oral suspension 800 mg/20 mL.
"The results of this proof-of-concept study are very encouraging," said Shankar Hariharan, Ph.D., executive vice president and chief scientific officer. "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."
"This study will prove highly instructive in the design of future clinical trials in Par's ongoing Megace® ES development program," added Dr. Hariharan.
Study Details
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.
Study Results
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.
Important Information
Par's recently approved Megace ES (megestrol acetate) 625 mg/ 5 mL concentrated oral suspension was not the dosage strength tested in this study. Par's development program 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.
Historical 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. For complete prescribing information, visit www.MegaceES.com.
About Par Pharmaceutical Companies
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. For press releases and other company information, visit www.parpharm.com.
Certain statements in this press release constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. To the extent any statements made in this news release contain information that is not historical, these statements are essentially forward-looking and are subject to risks and uncertainties, including the difficulty of predicting FDA filings and approvals, acceptance and demand for new pharmaceutical products, the impact of competitive products and pricing, new product development and launch, reliance on key strategic alliances, uncertainty of patent litigation filed against us, availability of raw materials, the regulatory environment, fluctuations in operating results and other risks and uncertainties detailed from time to time in the Company's filings with the Securities and Exchange Commission, such as the Company's Form 10-K, Form 10-Q, and Form 8-K reports.
Contacts:
Stephen Mock
(201) 802-4000
smock@parpharm.com
Cecelia C. Heer
(201) 802-4000
cheer@parpharm.com
*NanoCrystal® Technology is a trademark of Elan Pharma International Limited.
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