SPRING VALLEY, N.Y., Dec. 19 /PRNewswire-FirstCall/ -- Studies presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, D.C., showed that PAR-101 was potentially efficacious in treating C. difficile-associated diarrhea (CDAD).
According to Centers for Disease Control and Prevention data published in Morbidity and Mortality Weekly Report, CDAD has been a cause of some mortality and significant morbidity in hospitalized patients. More recent and less commonly encountered strains of CDAD are exhibiting significantly higher rates of mortality and have been less responsive to current treatments, such as metronidazole.
According to Sherwood L. Gorbach, MD, of Tufts University School of Medicine, "New strains of CDAD have emerged which are not responding to certain commonly used antibacterials. PAR-101 may provide healthcare professionals with a new tool to treat this potentially deadly bacterial illness. CDAD is highly contagious and has recurrence rates ranging from 20% to 25% after existing therapies. It is important that healthcare professionals have additional agents to treat this illness."
The Phase 1B study was a randomized, double-blind, multiple-dose, placebo- controlled study to evaluate pharmacokinetics, tolerance, and safety of PAR- 101 in healthy volunteers. Oral doses of PAR-101 150 mg, 300 mg, and 450 mg were administered once-daily for 10 days. PAR-101 was well tolerated by all subjects at all doses; no adverse events were considered to be drug related. The absorption of PAR-101 was minimal, with the majority of drug being eliminated in the feces.
In the proof-principle Phase 2A study, PAR-101 was evaluated in 45 CDAD patients in order to select an appropriate dose for subsequent trials. Subjects were randomized to receive either 50 mg, 100 mg, or 200 mg of treatment every twelve hours followed by clinical evaluation.
The clinical evaluation included relief of symptoms of CDAD, time to resolution of diarrhea, and clinical recurrence. Plasma and fecal samples were collected to investigate the relationship among dose, concentration, and excretion of PAR-101 in CDAD patients. PAR-101 was well tolerated by all subjects at all doses. Clinical response was as follows: only 2 patients in each of the two lower dose groups and none in the top dosing group were transferred to conventional therapy for apparent treatment failure (41/45, >91% cured overall). Of the subjects that completed therapy, 2/41 (<5%) patients had recurrence of symptoms within the 6 weeks of follow-up, one each in the low and high dose groups. After multiple dose oral administrations, plasma concentrations of PAR-101 were typically less than or equal to 5 ng/mL (0.005 mcg/mL) across the dose range, while fecal concentrations were high, averaging over 10,000 times the MIC90 for C. difficile at the top dose.
"PAR-101 has the potential to address an emerging health problem for both patients in hospitals and patients living in healthcare related environments. We are looking forward to the development of PAR-101 for this marketplace," said John MacPhee, president, Branded Products Division, Par Pharmaceutical Companies, Inc.
Clostridium difficile-associated diarrhea (CDAD)
C. difficile-associated diarrhea (CDAD), a potentially deadly bacterial illness, is the most common cause of nosocomial diarrhea in developed countries. CDAD is usually acquired in a hospital setting; almost all patients who develop this illness are taking, or have recently received, antibiotic therapy. The organism accounts for approximately 20% of cases of antibiotic-associated diarrhea as well as the majority of cases of antibiotic- associated colitis. Patients with diarrhea, especially if severe or accompanied by incontinence, may unintentionally spread the infection to other patients, and large outbreaks of CDAD have been observed in hospitals. Other symptoms may include abdominal pain and fever.
While there are commonly used therapies for the treatment of CDAD, including vancomycin (FDA-approved for this indication) and metronidazole, both have limitations in treating this illness. Based on clinical data, both agents are capable of inducing CDAD, and some patients do not respond to therapy with these agents and are at risk of developing more severe disease.
PAR-101 (formerly OPT-80)
PAR-101 is a narrow-spectrum antibiotic that is highly selective for C. difficile, thus preserving gut microbial ecology, an important consideration for the treatment of CDAD. It is believed that PAR-101 has the potential to address resistance to existing therapies and the increase of recurrence rates of CDAD. According to the Centers for Disease Control and Prevention, a virulent new strain of C. difficile has been linked to an eightfold increase in mortality in some outbreaks in the United States and Canada.
About Par Pharmaceutical Companies, Inc.
Par Pharmaceutical Companies, Inc. develops, manufactures and markets generic drugs and innovative branded pharmaceuticals for specialty markets. In 2005, Par received approval for and introduced Megace(R) ES, its first branded pharmaceutical product. Through its collaboration with Valeant Pharmaceuticals North America, Par expects to launch a second branded drug, Cesamet(TM), in early 2006.
Par's Generic Products Division is committed to providing high-quality pharmaceuticals that are affordable and accessible to patients. Par ranks 5th in sales among all U.S. generic companies, according to IMS Health, and currently manufactures, markets or licenses more than 90 generic drugs. For press release 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 Securities and Exchange Commission, such as the Company's Form 10-K, Form 10-Q, and Form 8-K reports.
Par Pharmaceutical Companies, Inc.CONTACT: Stephen J. Mock of Par Pharmaceutical Companies, Inc.,+1-201-802-4000, or smock@parpharm.com
Web site: http://www.parpharm.com/
