QUEBEC CITY, Sept. 30 /PRNewswire-FirstCall/ - AEterna Zentaris Inc., a global biopharmaceutical company focused on endocrine therapy and oncology, today reported that the 043 Thorough QT (TQT) trial, which is part of the cetrorelix pamoate clinical development program in benign prostatic hyperplasia (BPH), met its primary endpoint. Results showed that cetrorelix did not increase heart rate-corrected QT interval (QTc) at either time of observed maximal concentration of cetrorelix (CetroMax) or at the time of minimum level of serum testosterone (TestMin). Current guidance through the International Conference on Harmonization (ICH) E14 recommends that all new chemical entities undergo a TQT trial to assess their potential to induce QT interval changes. Therefore, this trial was conducted in accordance with ICH guidance. As announced on March 6, 2009, sanofi-aventis U.S. LLC, entered into an agreement with AEterna Zentaris for the development, registration and marketing of cetrorelix in BPH for the U.S. market.
About the 043 TQT Trial
The TQT trial titled, “Assessment of cetrorelix pamoate intermittent IM administration on ECG, PK and PD parameters in healthy male volunteers - a Thorough QT assessment to address the ICH-E14 guidelines”, involved 105 patients at one site, the MDS Pharma Services, Early Clinical Research unit in Phoenix, Arizona, under the supervision of principal investigator, Scott Sharples, M.D. This trial assessed the effects of cetrorelix pamoate on cardiovascular safety (QT/QTc interval assessment), as well as the pharmacokinetics (PK) and pharmacodynamics (PD) of the drug.
Healthy male subjects 50 to 70 years of age at the time of randomization were randomly allocated to receive, in a double-blind fashion, 2 intramuscular doses of cetrorelix 2 weeks apart (each dose equivalent to 52 mg peptide) or matching placebo. The study included a concurrent positive control group of subjects randomly assigned to receive a single oral dose of 400 mg moxifloxacin to establish assay sensitivity.
The primary endpoint was to show that cetrorelix did not increase heart rate-corrected QT interval (QTc; QTcF: Fridericia corrected) at either time of observed maximal concentration of cetrorelix (CetroMax) or at the time of minimum level of serum testosterone (TestMin).
Results
The study met its primary endpoint of showing the lack of an adverse effect of cetrorelix on the heart-rate corrected QT interval in line with the definition of a ‘negative’ study in the ICH Guideline E14. At all pre-specified times for the evaluation, the upper bound of the one-sided 95% confidence interval for the difference in QTcF from placebo was below 10 msec. At 48 hours, which was approximately the time of maximal concentration of cetrorelix, the difference in QTcF from placebo was 6.66 msec.
The study was appropriately designed as judged by the expected adverse effect of orally administered moxifloxacin, demonstrating the sensitivity of the trial to detect QTc prolongation. In addition, this study provided evidence that there was no QTc increase at DHTmin and also provided AEZS with more detailed information on the PK and PD characteristics of the drug which may be useful in future studies.
Juergen Engel, Ph.D., AEterna Zentaris President and CEO stated, “We are pleased that the study reached its main endpoint, particularly when taking into account that we used a supra-therapeutic dose of cetrorelix which is a dose that patients would not be receiving during treatment. As these encouraging results provide additional detailed information on the safety profile of cetrorelix, we remain committed to our Phase 3 program in BPH with this compound.”
About the Phase 3 Program with Cetrorelix in BPH
The cetrorelix pamoate Phase 3 program involves more than 1,600 patients with symptomatic BPH in Canada, the United States and Europe. In addition to the 043 TQT trial for which results were disclosed today, the program also encompasses 1 safety trial and 2 efficacy trials.
About Cetrorelix
Cetrorelix pamoate is an investigational agent that has shown in Phase 2 studies to provide fast and long lasting relief of BPH symptoms and was well tolerated, with a low incidence of sexual side effects. Cetrorelix is part of AEterna Zentaris’ luteinizing hormone-releasing hormone (LHRH) antagonist therapeutic approach. This peptide-based active substance was developed by the Company in cooperation with Nobel Prize winner Prof. Andrew Schally, currently of the U.S. Veterans Administration in Miami.
Cetrorelix acetate is marketed under the brand name Cetrotide®, the first LHRH antagonist approved for therapeutic use as part of in vitro fertilization programs (controlled ovulation stimulation/assisted reproductive technologies) in Europe, the USA and Japan. It was launched on the market through Serono (now Merck Serono) in the U.S., Europe and in several other countries, as well as in Japan through Shionogi.
About Benign Prostatic Hyperplasia
Benign prostatic hyperplasia (BPH) is one of the most common diseases of aging men - affecting more than 20 million men in the United States - but its etiology is far from being completely understood. Data from ongoing research suggest BPH and lower urinary tract symptoms (LUTS) are more complex conditions than once thought. While previous research on BPH etiology tended to focus on testosterone and other hormones, more recent research suggests other factors - including inflammation, various growth factors, and adrenoreceptors - actually may play a greater role in the development of BPH and LUTS.
BPH is associated with LUTS, including: frequent urination, a sudden, uncontrollable urge to urinate, waking at night to urinate (nocturia), difficulty starting a urine stream (hesitancy and straining), decreased strength of the urine stream (weak flow), feeling that the bladder is not completely empty, an urge to urinate again soon after urinating and pain during urination (dysuria). Currently available therapies may improve symptoms to some degree, but often come with sexual and other side effects.
About AEterna Zentaris Inc.
AEterna Zentaris Inc. is a global biopharmaceutical company focused on endocrine therapy and oncology, with proven expertise in drug discovery, development and commercialization. News releases and additional information are available at www.aezsinc.com.
Forward-Looking Statements
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