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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: PTI-428; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom, BT9 6AD
    • Celerion
  • Manchester, United Kingdom
    • Medicines Evaluation Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	Time Frame
Change in FEV1 over time	Baseline through Day 21
Change in sweat chloride over time	Baseline through Day 21
Change in weight over time	Baseline through Day 21
Change in nasal epithelial mRNA and protein expression over time	Baseline through Day 21

Collaborators and Investigators

• Sponsor: Proteostasis Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2017
• Primary Completion (Actual): October 3, 2018
• Study Completion (Actual): October 3, 2018

Study Registration Dates

• First Submitted: August 18, 2017
• First Submitted That Met QC Criteria: August 18, 2017
• First Posted (Actual): August 23, 2017

Study Record Updates

• Last Update Posted (Actual): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 24, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: PTI-428-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No