Sept. 20 /PRNewswire/ -- Phase III clinical data from 10 multi-national studies presented today at the 40th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Toronto found that KETEKTM (telithromycin) tablets may provide a convenient, once-daily, short-course treatment option for select respiratory tract infections (RTIs), including those infections caused by bacteria resistant to available therapies. Respiratory tract infections such as community-acquired pneumonia (CAP), acute bacterial exacerbations of chronic bronchitis (AECB), acute sinusitis, and tonsillitis/pharyngitis represent a significant societal burden, causing more than 50 million deaths globally each year.* (Logo: newscom.com )
KETEK is the first in a new family of antibiotics called ketolides. Ketolides are a novel addition to the macrolide-lincosamide-streptogramin (MLSb) group and are characterized by a broad microbiological spectrum, unique mechanism of action, and favorable resistance profile. KETEK combats resistant bacteria by inhibiting the protein synthesis necessary for bacterial reproduction, binding 10 times tighter than macrolides at two different sites on bacterial ribosomes. In vitro data suggest that it has a low propensity to induce bacterial resistance.
``Bacteria that cause community-acquired infections are growing increasingly resistant to antibiotics commonly prescribed to treat them,'' said Thomas File, M.D. Professor of Internal Medicine, Northeastern Ohio Universities College of Medicine. ``The level of activity we have seen with KETEK in Phase III clinical trials is an exciting development, and may provide the medical community with a new weapon in the fight against these troublesome infections.''
KETEK Phase III Clinical Trial Results
The 10 Phase III studies presented at ICAAC were comprised of data from almost 2,500 patients treated with KETEK and almost 1,800 patients treated with comparator antibiotics. KETEK showed a high level of activity against Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis; as well as atypical bacteria such as Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumoniae.
Community-Acquired Pneumonia (CAP)
Findings from three comparative Phase III studies - each designed to assess KETEK activity in the treatment of CAP - showed that KETEK once a day is as active as comparator drugs. A study, conducted throughout Europe and South Africa, showed that KETEK once a day was as active as high dose amoxicillin (1,000 mg) three times a day (94.6% vs. 90.1% clinical cure rate). Another study, conducted in North America, showed comparable activity between KETEK once a day and the macrolide clarithromycin (500 mg) twice a day (88.3% vs. 88.5% clinical cure rate) and a third study, also conducted in North America, demonstrated that KETEK once a day is as active as the fluoroquinolone trovafloxacin (200 mg) once a day (91.1% vs. 94.8% clinical cure rate).
Two sub-analyses of data from the North American study demonstrated that KETEK had a 90% clinical cure rate against S. pneumoniae - the most common cause of CAP.6 Another sub-analysis of North American and European study data demonstrated that KETEK is active against atypical respiratory bacteria including Chlamydia pneumoniae (93.3%), Mycoplasma pneumoniae (96.4%), Legionella pneumoniae (100%), and Coxiella burnetti (80%).
Acute Exacerbation of Chronic Bronchitis (AECB)
Results from two North American studies showed that KETEK was as active as comparator antibiotics with a shorter treatment duration in the treatment of chronic bronchitis complicated by a bacterial infections. The first study demonstrated that 800 mg of KETEK once a day for five days is well tolerated and as active as cefuroxime axetil 500 mg twice a day for 10 days (89.2% vs. 86.3% clinical cure rate). The second study showed that KETEK once a day for a five day period is as active as amoxycillin/clavulanic (amox/clav) acid (500 mg/125 mg, respectively) three times a day for 10 days (86.1% vs. 82.1% clinical cure rate).
Sinusitis
In a North American study conducted to examine the clinical and bacteriological efficacy in sinusitis, KETEK 800 mg once a day for five or 10 days was compared with a 10-day regimen of amoxicillin/clavulanic acid in 790 patients. KETEK administered for five days was as active (75.8% clinical cure rate) as a 10-day course of the comparator (74.6%); and as active as a 10-day course of KETEK (74.1% clinical cure rate). Another study of 336 sinusitis patients in Europe and North America confirmed comparable cure rates between the 5-day and 10-day regimens (91.1% vs. 91.0% clinical cure rate). Patients in the study received either 10 days of KETEK or five days of KETEK followed by a placebo for five days. KETEK-susceptible bacteria isolated from the sinusitis patients included S. pneumoniae, H. influenzae, M. catarrhalis, and S. aureus.
Pharyngitis/Tonsillitis
A study was conducted in Europe to test the clinical efficacy of 800 mg of KETEK once a day for five days as compared to 500 mg of penicillin V three times a day for 10 days. Patients who took KETEK only five times had cure rates comparable to those whose regimen included either 20 or 30 doses of penicillin V (KETEK 94.8% vs. penicillin V 94.1% clinical cure rate). In a second study, conducted in North America, KETEK taken for only five days demonstrated equivalence in clinical and bacteriological cure to clarithromycin (91.3% vs. clarithromycin 88.1% clinical cure rate), which was taken over the course of 10 days in the treatment of pharyngitis or tonsillitis caused by group A Beta-hemolytic streptococci.
In those studies for which side effects were cited, the most common adverse events included diarrhea (8.3%-23.9%), nausea (2.9%-11.7%), dizziness (1.3%-7.4%), and headache (4.1%-6.6%).
Aventis submitted applications for KETEK to the U.S. Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) in March 2000. The company is seeking approval for a once-daily dosing regimen for CAP, AECB, and acute sinusitis in patients 18 and older, as well as pharyngitis/tonsillitis in patients age 13 and older; and a short-course treatment regimen (once a day for five days) in all indications except CAP (once a day for seven to 10 days). |
