Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis
Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis
The study is a randomized, double-blind, placebo-controlled, study that will be conducted at
 multiple centers in subjects with Cystic Fibrosis (CF) who are either homozygous for the
 F508del mutation or heterozygous with at least copy of the F508del mutation.
Study PTI-808-02 will enroll up to approximately 32 subjects. Subjects in the first cohort
 will receive PTI-808 and PTI-801. Following completion of Cohort 1, initiation of enrollment
 into subsequent cohorts will be based upon review and approval by the Safety Review Committee
 (SRC).
Inclusion Criteria:

 -  Cohorts 1,2 and 4: A Confirmed diagnosis of CF with the F508del/F508del CFTR genotype
 on record, along with clinical findings consistent with CF such as chronic
 sinopulmonary disease or gastrointestinal/nutritional abnormalities

 -  Cohort 3 only: Confirmed diagnosis of CF with at least one copy of the F508del CFTR
 mutation on record, along with clinical findings consistent with CF, such as chronic
 sinopulmonary disease or gastrointestinal / nutritional abnormalities

 -  Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive

 -  Non-smoker and non-tobacco user for a minimum of 30 days prior to screening

 -  Cohort 3 only: A sweat chloride value of ≥60 mmol/L based on quantitative pilocarpine
 iontophoresis (as documented in the subject's medical record or as confirmed at the
 screening visit)

 Exclusion Criteria:

 -  Currently taking or has taken a CFTR modulator within 30 days prior to initial dose of
 study drugs

 -  Participation in another clinical trial or treatment with an investigational agent
 within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1

 -  History of cancer within the past 5 years

 -  History of organ transplantation

 -  Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically
 significant infection or illness (as determined by the investigator) requiring an
 increase or addition of medication, such as antibiotics or corticosteroids, within 14
 days of Day 1

 -  Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline,
 azithromycin, Pulmozyme®, Cayston®, TOBI®) or any change in chronic therapy (excluding
 pancreatic enzyme replacement therapy) within 28 days prior to Day 1

 -  History or current evidence of alcohol or drug abuse or dependence within 12 months of
 screening as determined by the investigator

 -  Pregnant or nursing women