study assessing pti-428 safety, tolerability, and pharmacokinetics in subjects with cystic fibrosis

Conditions: Cystic Fibrosis

Summary: this trial will consist of three arms: part a, part b, and part c. part a has two groups. the first group will enroll adult subjects with cystic fibrosis (cf) into a single ascending dose (sad) treatment group. the second group will enroll adult subjects with cf, including those on background treatment with orkambi® and those not on a cystic fibrosis transmembrane conductance regulator (cftr) modulator, into a multiple ascending dose (mad) treatment group. part b will enroll adult subjects with cf currently on stable orkambi® background therapy for a minimum of 3 months into a phase ii treatment group consisting of two cohorts. part c will enroll adult subjects with cf, including those on background treatment with kalydeco® and those not on a cftr modulator, into a phase ii treatment group consisting of three cohorts. approximately 136 subjects will be enrolled.

part a the sad treatment group is comprised of 3 cohorts where subjects will be randomized to either pti-428 or placebo. following the conclusion of at least 3 sad treatment groups, a set of adult subjects diagnosed with cf will participate in an assigned mad treatment group. the mad treatment group is comprised of 3 cohorts. mad cohort 1 will enroll adult subjects with cf currently on stable orkambi® background therapy for a minimum of 3 months at the time of randomization. mad cohorts 2 and 3 will enroll adult subjects with cf who are not currently on any background therapies. subjects in all mad cohorts will be randomized to either pti-428 or placebo. each dose will be administered once daily (qd) for a total of 7 days. part b following the conclusion of mad cohort 1, a set of adult subjects diagnosed with cf currently on stable orkambi® background therapy for a minimum of 3 months will participate in part b. the part b phase ii treatment group is comprised of 2 cohorts where subjects will be randomized to either pti-428 or placebo. each dose will be administered qd for a total of 28 days. part c following the conclusion of part b phase ii, a set of adult subjects diagnosed with cf will participate in part c. the part c phase ii treatment group is comprised of 3 cohorts. part c cohort 1 will enroll adult subjects with cf who are eligible to take, but not currently taking, orkambi® in accordance with the approved label. part c cohort 2 will enroll adult subjects with cf currently on stable kalydeco® background therapy for a minimum of 3 months at the time of randomization. part c cohort 3 will enroll adult subjects with cf who are not currently on any background therapies and are pancreatic sufficient. each pti-428 or placebo dose will be administered qd for a total of 28 days.

Eligibility criteria:
inclusion criteria: * confirmed diagnosis of cf. * forced expiratory volume in 1 second (fev1) 40-90% predicted. * non-smoker and non-tobacco user for a minimum of 30 days prior to screening and for the duration of the study. exclusion criteria: * participation in another clinical trial or treatment with an investigational agent within 30 days or 5 half-lives, whichever is longer, prior to study day 1. * history of cancer within the past five years (excluding cervical cis with curative therapy for at least one year prior to screening and non-melanoma skin cancer). * history of organ transplantation. * any sinopulmonary infection or cf exacerbation requiring a change or addition of medication (including antibiotics) within 1 month of study day 1 or any other clinically significant infection as determined by the investigator within 1 month of day 1. * history of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator. * male and female of child-bearing potential, unless they are using highly effective methods of contraception during participation in the clinical study and for 4 weeks after termination from study. * pregnant or nursing women.