Study Assessing PTI-428 Safety, Tolerability, and Pharmacokinetics in Subjects With Cystic Fibrosis on KALYDECO® as Background Therapy

Study Overview
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Brief Summary
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The trial will consist of a single treatment group enrolling adult subjects with CF on background therapy with KALYDECO®. Approximately 16 subjects will be enrolled.

Detailed Description
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The single treatment group will enroll adult subjects with CF currently on stable KALYDECO® background therapy for a minimum of 3 months at the time of randomization. Subjects will be randomized to either PTI-428 or placebo. Each dose will be administered once daily (QD) for a total of 14 Days. The subjects will continue treatment with KALYDECO® throughout the study.

Official Title
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A Phase I, Randomized, Placebo-Controlled, Study Designed to Assess the Safety, Tolerability, and Pharmacokinetics of PTI-428 in Subjects With Cystic Fibrosis.

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: PTI-428
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of CF. Stable on Kalydeco dosing for both label indication and per label dosing for a minimum of 3 months at the time of randomization 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PTI-428<br>Subjects will receive once daily dosing of PTI-428 or placebo for 14 days. | Drug: PTI-428<br>* PTI-428 or placebo will be given QD for 14 days.<br>|
| Placebo Comparator: Placebo<br>Subjects will receive once daily dosing of PTI-428 or placebo for 14 days. | Drug: Placebo<br>* PTI-428 or placebo will be given QD for 14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as assessed by adverse events, safety labs, electrocardiograms (ECGs), physical examinations, and vital signs |  | Baseline through Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| t1/2 of multiple oral doses |  | Baseline through Day 14 | 
| Tmax of multiple oral doses |  | Baseline through Day 14 | 
| Cmax of multiple oral doses |  | Baseline through Day 14 | 
| AUC0-t of multiple oral doses |  | Baseline through Day 14 |