NewsMonday, 10. November 2008
Successful Clinical Trials for Tobramycin 100 & Investigational eFlow for CF
PARI Pharma Completes Successful Clinical Trials for
Tobramycin 100 & Investigational eFlow for CF
MONTEREY, CALIFORNIA, NOVEMBER 10, 2008 – PARI Pharma GmbH has successfully completed Phase I and Phase II clinical trials comparing its proprietary PARI Tobramycin 100 (150mg/1.5mL)formulation delivered via a customized Investigational eFlow Nebulizer System to TOBI (tobramycin300mg/5mL) delivered with the PARI LC PLUS jet nebulizer. While key deposition and safety thresholds were maintained, the marked difference was a reduction in the average inhalation time to 4 – 4 1/2minutes for the PARI Tobramycin 100, down from 16 - 17 minutes for the TOBI therapy. PARI Tobramycin 100 is an investigational therapy for cystic fibrosis patients with Pseudomonas aeruginosa infections.
Results for both formulations show no difference in the ratio of peripheral to central lung deposition. Maximum tobramycin serum levels were below recommended safety thresholds for systemic and inhaled tobramycin applications, and both tobramycin sputum concentrations and the adverse reaction rates were similar. It appears that, for a twice-daily treatment with PARI Tobramycin 100 delivered via an Investigational eFlow, approximately 10 hours+ per month of inhalation time can be saved compared to TOBI.
“We believe that advancements in our eFlow Technology platform can provide a significant reduction in treatment time while reducing the amount of drug needed to deliver an effective dose – a true advancement for patients with CF. The results of our Phase I and Phase II trials are encouraging for both the formulation and the optimized delivery device. Same lung deposition, less drug product, shorter inhalation times, and the chance to improve compliance – these are real life improvements. Focusing on drug formulation and device optimization as one project allows us to make these advancements. Our goal is to reduce the burden of treatment for CF patients,” said Dr. Manfred Keller, executive vice president and chief scientific officer at PARI Pharma.
“We were very pleased to see similar lung deposition and safety profiles while using a lower dose andvolume of tobramycin,” said Dr. Allan Coates, lead researcher from the Hospital for Sick Kids in Toronto, Canada. “Technology is really working on the side of the patient with this formulation and the resulting reductions in treatment times. Lack of patient adherence to recommended therapy is a major challenge incystic fibrosis, especially in adolescents, with the length of treatment time given as the major excuse. With equivalent delivery but in a much shorter time, there are improved chances for greater adherence to prescribed therapy.
"Based on the successful results of the Phase I and Phase II clinical trials, regulatory bodies in Europe welcomed the advantages and benefit of PARI Tobramycin 100 for CF patients and recommended moving forward with a Phase III study to demonstrate therapeutic efficacy and equivalence to TOBI.
PARI Pharma is currently in discussions with multinational pharmaceutical companies to evaluate the efficacy of PARI Tobramycin 100 in a Phase III clinical study and to ultimately make this next-generation treatment available to CF patients worldwide. The Phase I clinical trial was a randomized, open label, crossover, single-dose deposition study of PARI Tobramycin 100 in an Investigational eFlow versus TOBI/LC PLUS in 16 cystic fibrosis patients, including8 adults and 8 children. The study was conducted by Dr. Allan Coates at the Hospital for Sick Kids in Toronto, Canada. Tobramycin lung deposition for both applications was between 46mg and 47mg. There was also no difference in the ratio of peripheral to central lung deposition between both drug products and delivery systems. Results from the study were presented at the North American Cystic Fibrosis Conference in October.
The Phase II clinical trial, a randomized, open label, parallel group, non-inferiority, 28-daypharmacokinetic study evaluated the serum levels after twice daily inhalation of PARI Tobramycin 100versus TOBI in 86 cystic fibrosis patients. The study was conducted in several CF centers in Germany and Poland. The primary endpoint was the maximum tobramycin serum level (C max ) as safety surrogate parameter at day seven. The PARI Tobramycin 100 C max level for the overall, adult and non-adult population was 1.29, 1.21 and 1.36 mg/L, compared to 1.65, 1.81 and 1.52 mg/L, respectively, for the TOBI group. Based on a 30% margin and 90% confidence intervals, PARI Tobramycin 100 achievednon-inferiority in the overall, adult and children population (p < 0.001 to 0.02). All C max values were well below recommended safety thresholds for systemic and inhaled tobramycin applications. Tobramycinsputum concentrations were similar and the adverse reaction rate after 28 days of tobramycin inhalation was comparable for both treatment regimes. There was a marked reduction in the mean inhalation time from 16.0 min for TOBI to 4.6 min for the PARI Tobramycin 100 application.
About PARI Tobramycin 100
PARI Tobramycin 100 is an investigational proprietary aqueous solution of 150mg tobramycin/1.5mL for inhalation delivery via a customized Investigational eFlow Nebulizer System, both developed by PARI Pharma, as a potential treatment for patients suffering from bacterial infections caused by Pseudomonasaeruginosa. Patents on both the drug formulation and device were granted in Europe and several other countries. Low volume/high concentration drug products such as PARI Tobramycin 100 delivered using eFlow Technology have shown to substantially shorten nebulized treatments and are believed to become a major relief in patients’ lives.
About the Investigational eFlow Nebulizer System
and eFlow Technology
The Investigational eFlow Nebulizer System uses eFlow Technology to enable highly efficient aerosolization of liquid medications via a vibrating, perforated membrane that includes thousands of small holes that produce the aerosol mist. Compared to other nebulization technologies, eFlow Technology produces aerosols with a very high density of active drug, a precisely defined droplet size, and a high proportion of respirable droplets delivered in the shortest possible period of time. Combined with its silent mode of operation, small size (it fits in the palm of your hand), light weight, and battery use, products incorporating eFlow Technology reduce the burden of taking daily, inhaled treatments. The Investigational eFlow Nebulizer System and eFlow Technology are proprietary to PARI Pharma.
PARI Pharma partners with pharmaceutical companies to develop new or improved therapies with eFlow Technology and other advanced delivery platforms. Investigational eFlow Nebulizer Systems areoptimized and customized per investigational drug product and are currently in clinical trials for cysticfibrosis, asthma, COPD, respiratory syncytial virus (RSV) infection, and treatments for lung transplant patients among other indications.
About PARI Pharma
PARI Pharma focuses on the development of aerosol delivery devices, drug formulations, and therapies. Based on PARI’s 100-year history working with aerosols, PARI Pharma develops treatments for pulmonary and nasal administration optimized with advanced delivery technologies, such as eFlow Technology. PARI Pharma provides comprehensive inhalation drug development, including nebulizer formulation development and optimization, analytics, aerosol characterization, clinical protocol development, and regulatory guidance, all in compliance with CMC/GCP guidelines. PARI Pharma has several clinical development programs ongoing, either partnered or on its own. PARI Pharma, a PARI Medical Holding company, is located in Munich, Germany with a major presence in the United States. Online at www.paripharma.com
Additional information on eFlow Technology is available by contacting Kirsten Ayars at +1 805-452-7909or Geoff A. Hunziker at +1 831-372-3580. For more on PARI Tobramycin 100 and eFlow Technology, please contact Dr. Robert Phelps at +49 89 742846-69.