MAPP » Topics » UDB Clinical Development Program

This excerpt taken from the MAPP 10-K filed Mar 12, 2009.

UDB Clinical Development Program

In a Phase 2 clinical trial, UDB was effective in improving asthma symptoms and was well tolerated when compared to placebo. Nebulization time was three to five minutes. In February 2009, we announced top-line results from our first Phase 3 trial of UDB, indicating that the trial did not meet its co-primary endpoints in the two doses evaluated when compared to placebo. We and our partner AstraZeneca are conducting further analyses of these data to determine appropriate next steps for the UDB program.

Phase 2 Clinical Trial Results. In February 2007, we announced positive results from a Phase 2 clinical trial of UDB as a potential treatment for asthma in children. The clinical trial included 205 asthmatic children aged one to 18 years old across multiple sites in the United States. The objective of the clinical trial was to evaluate the efficacy, tolerability and pharmacokinetics of UDB. The clinical trial compared two different doses of UDB, 0.135 mg and 0.25 mg, administered twice a day, in a randomized, double-blind, placebo-controlled trial. The co-primary endpoints of the clinical trial were the change from baseline in Nighttime Composite Symptom Score, which is a composite of the three symptoms of coughing, wheezing and shortness of breath, and the change from baseline in Daytime Composite Symptom Score in the same three symptoms. Secondary endpoints included changes from baseline in morning and evening peak expiratory flow, a measure of lung function. In addition, we evaluated trends in Forced Expiratory Volume in one second, or FEV, which indirectly measures airway narrowing.

This Phase 2 clinical trial demonstrated that after six weeks of dosing, UDB produced a statistically significant reduction in Nighttime and Daytime Composite Symptom Scores versus placebo for the 0.135 mg dose of UDB (p = 0.002 for the nighttime score and p = 0.003 for the daytime score). A p-value of 0.05 or less generally represents statistical significance. Positive trends in FEV1 were seen in those patients old enough to take this test. The higher 0.25 mg twice a day dose was not significantly better than placebo in the co-primary endpoints of Nighttime and Daytime Composite Symptom Score. However, we observed consistent trends with respect to secondary endpoints and similar magnitude of FEV1 improvements in both doses compared to placebo, which we believe is sufficient to support future clinical evaluation of the 0.25 mg dose.

The clinical trial showed both doses of UDB to be well tolerated, with no serious adverse events reported. There were no incidences of oral thrush. Also, there was no reduction in cortisol levels as compared to placebo over the duration of the clinical trial. Suppression of cortisol, a natural steroid hormone produced by the body, correlates with the occurrence of systemic side effects from the administration of high dose ICSs. Therefore, cortisol levels are often measured as an indication of systemic side effects from the administration of ICSs. Patients experienced average nebulization times of three to five minutes, which steadily decreased over the course of the clinical trial period.

Phase 3 Clinical Trial Results. In February 2009, we announced top-line results from our first Phase 3 trial of UDB, indicating that the trial did not meet its co-primary endpoints, asthma control as assessed by changes from baseline in nighttime and daytime composite symptom scores, in the two doses evaluated, when compared to placebo.

In this randomized, double-blind, placebo-controlled study, 360 steroid naïve children with asthma, 12-months to eight years of age, were randomized to receive 0.25 mg UDB, 0.135 mg UDB or placebo twice a day over a 12-week period. The co-primary endpoints evaluated asthma control as assessed by changes from baseline as compared to placebo in nighttime composite symptom scores, and daytime composite symptom scores, both comprised of cough, wheeze and shortness of breath. Based on our initial review of these data, both

 

8


Table of Contents

the placebo and study groups experienced improvements in asthma symptoms, but the differences between placebo and active were not statistically significant. We observed a higher than expected response in the placebo group, starting as early as one week after randomization and continuing throughout the 12-week treatment period. Median nebulization times were less than four minutes for both doses in the study. Initial review of the data has not identified any serious adverse events attributed to the study drug. Patients continue to be treated in a long-term safety study to collect long-term safety data on the two doses under investigation.

Remaining Development Program. We and our partner AstraZeneca are conducting further analyses of data from our first Phase 3 clinical trial of UDB to determine appropriate next steps for the program.

Because budesonide is well characterized and previously approved, we may seek FDA marketing approval of UDB under Section 505(b)(2) of the FFDCA. Section 505(b)(2) of the FFDCA provides an alternate path to FDA approval for modifications to formulations of products previously approved by the FDA. Section 505(b)(2) permits the filing of an NDA where at least some of the information required for approval comes from clinical trials not conducted by or for the applicant and for which the applicant has not obtained a right of reference. This may expedite the development program for UDB by potentially decreasing the overall scope of work we must do ourselves.

This excerpt taken from the MAPP 10-K filed Mar 20, 2008.

UDB Clinical Development Program

UDB has been shown in our clinical studies to be effective in improving asthma symptoms and to be well tolerated when compared to placebo. Nebulization time has been shown to be three to five minutes. We

 

7


Table of Contents

announced positive results from a Phase 2 clinical trial in February 2007, and we initiated a Phase 3 clinical program for UDB in pediatric asthmatics in January 2008.

Phase 2 Clinical Trial Results. In February 2007, we announced positive results from a Phase 2 clinical trial of UDB as a potential treatment for pediatric asthma. The trial included 205 asthmatic children aged one to 18 years old across multiple sites in the United States. The objective of the study was to evaluate the efficacy, tolerability and pharmacokinetics of UDB. The study compared two different doses of UDB, 0.135 mg and 0.25 mg, administered twice a day, in a randomized, double-blind, placebo-controlled trial. The co-primary endpoints of the study were the change from baseline in Nighttime Composite Symptom Score, which is a composite of the three symptoms of coughing, wheezing and shortness of breath, and the change from baseline in Daytime Composite Symptom Score in the same three symptoms. Secondary endpoints included changes from baseline in morning and evening peak expiratory flow, a measure of lung function. In addition, we evaluated trends in Forced Expiratory Volume in one second, or FEV, which indirectly measures airway narrowing.

This Phase 2 clinical trial demonstrated that after six weeks of dosing, UDB produced a statistically significant reduction in Nighttime and Daytime Composite Symptom Scores versus placebo for the 0.135 mg dose of UDB (p = 0.002 for the nighttime score and p = 0.003 for the daytime score). A p-value of 0.05 or less generally represents statistical significance. Positive trends in FEV1 were seen in those patients old enough to take this test. The higher 0.25 mg twice a day dose was not significantly better than placebo in the co-primary endpoints of Nighttime and Daytime Composite Symptom Score. However, we observed consistent trends with respect to secondary endpoints and similar magnitude of FEV1 improvements in both doses compared to placebo, which we believe is sufficient to support future clinical evaluation of the 0.25 mg dose.

The study showed both doses of UDB to be well tolerated, with no serious adverse events reported. There were no incidences of oral thrush. Also, there was no reduction in cortisol levels as compared to placebo over the duration of the study. Suppression of cortisol, a natural steroid hormone produced by the body, correlates with the occurrence of systemic side effects from the administration of high dose ICSs. Therefore, cortisol levels are often measured as an indication of systemic side effects from the administration of ICSs. Patients experienced average nebulization times of three to five minutes, which steadily decreased over the course of the study period.

Phase 3 Clinical Program. We are currently conducting a Phase 3 pivotal efficacy clinical trial to provide evidence of efficacy and safety of UDB for the treatment of pediatric asthma. The first Phase 3 trial, which we initiated in January 2008, is a multi-center, randomized, double-blind, placebo controlled efficacy and safety trial in approximately 360 asthmatic children 12 months to eight years of age. Patients are randomized to either a 0.25 mg dose of UDB, a 0.135 mg dose of UDB or placebo given twice a day over a 12 week treatment period. The primary efficacy endpoint is the change from baseline for both Nighttime and Daytime Composite Symptom scores. We will follow these patients in a long-term safety extension study. Our second Phase 3 trial will be a confirmatory efficacy trial with a similar design to the first Phase 3 trial. We also plan to conduct the following additional two pharmacokinetic trials: a 14 day active controlled crossover trial in approximately 30 adult asthmatics; and a 12 week active controlled trial in approximately 100 patients.

Because budesonide is well characterized and previously approved, we may seek FDA marketing approval of UDB under Section 505(b)(2) of the FFDCA. Section 505(b)(2) of the FFDCA provides an alternate path to FDA approval for modifications to formulations of products previously approved by the FDA. Section 505(b)(2) permits the filing of an NDA where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference. This may expedite the development program for UDB by potentially decreasing the overall scope of work we must do ourselves.

 

8


Table of Contents

EXCERPTS ON THIS PAGE:

10-K
Mar 12, 2009
10-K
Mar 20, 2008
Wikinvest © 2006, 2007, 2008, 2009, 2010, 2011, 2012. Use of this site is subject to express Terms of Service, Privacy Policy, and Disclaimer. By continuing past this page, you agree to abide by these terms. Any information provided by Wikinvest, including but not limited to company data, competitors, business analysis, market share, sales revenues and other operating metrics, earnings call analysis, conference call transcripts, industry information, or price targets should not be construed as research, trading tips or recommendations, or investment advice and is provided with no warrants as to its accuracy. Stock market data, including US and International equity symbols, stock quotes, share prices, earnings ratios, and other fundamental data is provided by data partners. Stock market quotes delayed at least 15 minutes for NASDAQ, 20 mins for NYSE and AMEX. Market data by Xignite. See data providers for more details. Company names, products, services and branding cited herein may be trademarks or registered trademarks of their respective owners. The use of trademarks or service marks of another is not a representation that the other is affiliated with, sponsors, is sponsored by, endorses, or is endorsed by Wikinvest.
Powered by MediaWiki