The Cystic Fibrosis Therapeutics Development Network and CF

Clinical Research at UNM

Jennifer L. Taylor-Cousar, MDAssistant Professor,

Adult CF Program/Associate CF Center Director,

University of New Mexico CF CenterMarch 19, 2009

CF Therapeutics Development Network (CF TDN)

• CF TDN– Initially created in 1982 (Research

Development Center)– In 2008 made up of 18 centers– With increasing number of potentially

therapeutic drugs, it became clear that there were not enough patients at these 18 centers• 2 years ago, RFA distributed to increase number

of CF research centers• In January 2009, UNM became part of the CF

TDN

Cystic Fibrosis TherapeuticsDevelopment

Pipeline

Summary of pH Cascade in CF

Altered pH in CF cells

Abnormal glycosylation pattern

Predisposition to adherence by P. aeruginosa

Inflammatory response

Chronic lung damage/early death

CFTR Mutation

PDEi

Sildenafil (Revatio™) in CF

CFTRwt ENaC

H+

Na+

Normal cell

H+

ENaCCFTRm

CF cell

Inflammation

Infection

Na+

H+

ENaCCFTRm

CF cell

sildenafil

CFTRm ENaC

H+

Na+

CF Cell

Inflammation

Infection

Study Design

• Placebo-controlled, blinded, randomized cross-over study of sildenafil in clinically stable patients with mild to moderate CF lung disease– Length of participation for each subject will be

approximately 15 weeks, and will consist of: • Screening visit • Two outpatient study visits with initiation of study drug and/or

placebo • One interim visit during each therapy period (to review

concomitant medications and assess side effects) • One visit at the end of each therapy period (to reassess

inflammatory markers, laboratory studies and side effects) • A 28-day washout period with coordinator phone call • A follow-up assessment 2 weeks after subject completion