ATS 2009: Inhalation Powder Tobramycin Safe, Effective to Treat Pseudomonas aeruginosa in Cystic Fibrosis Patients

Kristina Rebelo

May 18, 2009

May 18, 2009 (San Diego, California) — A new pocket-sized drug device using a tobramycin inhalation powder (TIP) might offer not only a shorter administration time (4 to 6 minutes twice daily) in the treatment of cystic fibrosis patients infected with Pseudomonas aeruginosa (Pa), but also improved lung function and decreased Pa density, according to phase 3 study results released here at ATS 2009: American Thoracic Society International Conference.

"The current treatment for Pa infection is with tobramycin inhalation solution (TOBI), and that must be nebulized for 15 to 20 minutes (plus cleaning and sterilization) 2 times a day, on and off cycling," lead investigator Michael W. Konstan, MD, pediatric pulmonologist, professor, and director of the Rainbow Babies & Children's Hospital LeRoy W. Matthews Cystic Fibrosis Center, part of University Hospitals Case Medical Center in Cleveland, Ohio, told Medscape Pulmonary Medicine at his poster before his oral presentation. "That's a therapy with a big burden and patients are not adhering to therapy, so Novartis is developing a dry powder form of treatment to serve as an alternative to TOBI."

Dr. Michael Konstan

The primary efficacy measure was the relative change in forced expiratory volume in 1 second (FEV1) from day 1 to day 28 in the first cycle. The secondary objectives of the study were to assess antibiotic use for Pa, respiratory-related hospitalizations, and changes in sputum Pa density and safety.

This was a multicenter international 3-cycle, 2-group study conducted at 48 sites in 8 countries in Europe, Latin America, and the United States that assessed the efficacy and safety relative to placebo of the new formulation TIP in 102 cystic fibrosis patients aged 6 to 21 years (FEV1 ≥ 25% ≤ 80% predicted). In cycle 1, patients were randomized in a double-blind 1:1 manner to receive TIP (112 mg twice daily) administered with the T-326 dry-powder inhaler or matching placebo capsules; in cycles 2 and 3, all patients received open-label TIP.

This study reported results for cycle 1 — TIP vs placebo. Treatment with TIP met its primary end point, in that it significantly improved the relative change from baseline (13% improvement) in FEV1 (predicted difference, 13.3; 95% confidence interval, 5.31 - 21.28; P = .0016). TIP reduced sputum Pa density by about 2-log10 colony-forming units. Fewer patients (19.6%) receiving TIP required antibiotic use than those receiving placebo (32.7%), and duration of use was shorter. There were no hospitalizations among the TIP group for respiratory adverse events, with 12.2% of patients taking placebo requiring respiratory-related hospitalization. Most of the adverse events in the placebo group, Dr. Konstan said, included cough and sore throat.

"TIP appears to be well tolerated and beneficial for therapy in patients with [cystic fibrosis]," said Dr. Konstan. "It will really help our patients with respiratory pathogens to have a therapy that is easier to take."

Another study has compared TIP to TOBI; however, those results have not yet been published, Dr. Konstan said.

Commenting on Dr. Konstan's study presentation was Jeffrey S. Wagener, MD, from the Departments of Pediatric Pulmonology and Pediatrics, The Children's Hospital, and Professor of Pediatrics, University of Colorado Denver School of Medicine in Aurora, who gave a presentation in the same session entitled, "A Tool for Predicting Risk of Future Lung Function Decline in Cystic Fibrosis Patients."

He told Medscape Pulmonary Medicine that if any treatment was more technically convenient, there could be greater adherence. "Cystic fibrosis is a tough disease, but patients don't recognize how bad it can be," he said. "Currently, patient adherence to 20-minute therapy twice a day is low, and the expectation is that shortening the treatment will increase adherence, but the challenge is: Will it be equally effective? There are also the challenges of dry powder and what the competitive environment will be. For years, Novartis had no competition and there are several competitors out there now. It's always about patient perception, but efficacy is key."

Dr. Konstan reports that he is a consultant to Novartis Pharmaceutical Corporation and that his institution receives research grants from Novartis. Dr. Wagener has disclosed no relevant financial relationships.

ATS 2009: American Thoracic Society International Conference: Poster 804. Presented May 17, 2009.

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