Study Assessing PTI-428 Safety, Tolerability, and Pharmacokinetics in Subjects With Cystic Fibrosis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02718495
• Date of registration: 10/03/2016
• Prospective Registration: Yes
• Primary sponsor: Proteostasis Therapeutics, Inc.
• Public title: Study Assessing PTI-428 Safety, Tolerability, and Pharmacokinetics in Subjects With Cystic Fibrosis
• Scientific title: A Phase I/II, Multi-center, Randomized, Placebo-Controlled, Study Designed to Assess the Safety, Tolerability, and Pharmacokinetics of PTI-428 in Subjects With Cystic Fibrosis
• Date of first enrolment: July 19, 2016
• Target sample size: 56
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02718495
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

Canada, Czechia, Denmark, France, Germany, United Kingdom, United States

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Placebo

Drug: PTI-428

Primary Outcome(s)

Part C Cohort 1: safety and tolerability as assessed by adverse events, safety labs: hematology, chemistry, and urinalysis, electrocardiograms (ECGs), physical examinations, and vital signs [Time Frame: Baseline to Day 49]

MAD: safety and tolerability as assessed by adverse events, pulomonary function tests, safety labs: hematology, chemistry, and urinalysis, electrocardiograms (ECGs), physical examinations, and vital signs [Time Frame: Baseline to Day 14]

SAD: safety and tolerability as assessed by adverse events, safety labs: hematology, chemistry, and urinalysis, electrocardiograms (ECGs), physical examinations, and vital signs [Time Frame: Baseline to Day 7]

Part B and Part C Cohorts 2 and 3: safety and tolerability as assessed by adverse events, safety labs: hematology, chemistry, and urinalysis, electrocardiograms (ECGs), physical examinations, and vital signs [Time Frame: Baseline to Day 35]

Secondary Outcome(s)

MAD: AUC0-t of multiple oral doses [Time Frame: Baseline through 24 hours post Day 7 dose]

Part B and Part C Cohorts 2 and 3: change in forced expiratory volume in one second (FEV1) over time [Time Frame: Baseline through Day 35]

MAD: Tmax of multiple oral doses [Time Frame: Baseline through 24 hours post Day 7 dose]

Part B and Part C Cohorts 2 and 3: AUC0-8 of multiple oral doses [Time Frame: Baseline through 24 hours post Day 28 dose]

Part C Cohort 1: AUC0-8 of multiple oral doses [Time Frame: Baseline through Day 42]

Part C Cohort 1: Cmax of multiple oral doses [Time Frame: Baseline through Day 42]

Part C Cohort 1: Tmax of multiple oral doses [Time Frame: Baseline through Day 42]

SAD: maximum plasma concentration (Cmax) of single oral dose [Time Frame: Baseline through 72 hours post dose]

Part C Cohort 1: AUC0-t of multiple oral doses [Time Frame: Baseline through Day 42]

Part C Cohort 1: change in sweat chloride over time [Time Frame: Baseline through Day 49]

Part B and Part C Cohorts 2 and 3: Tmax of multiple oral doses [Time Frame: Baseline through 24 hours post Day 28 dose]

Part B and Part C Cohorts 2 and 3: AUC0-t of multiple oral doses [Time Frame: Baseline through 24 hours post Day 28 dose]

Part C Cohort 1: change in FEV1 over time [Time Frame: Baseline through Day 49]

SAD: time to reach maximum plasma concentration (Tmax) of single oral dose [Time Frame: Baseline through 72 hours post dose]

Part B and Part C Cohorts 2 and 3: change in sweat chloride over time [Time Frame: Baseline through Day 35]

Part B and Part C Cohorts 2 and 3: change in weight over time [Time Frame: Baseline through Day 35]

MAD: area under the concentration-time curve from time 0 to infinity (AUC0-8) of multiple oral doses [Time Frame: Baseline through 24 hours post Day 7 dose]

MAD: Cmax of multiple oral doses [Time Frame: Baseline through 24 hours post Day 7 dose]

MAD: t1/2 of multiple oral doses [Time Frame: Baseline through 24 hours post Day 7 dose]

Part B and Part C Cohorts 2 and 3: t1/2 of multiple oral doses [Time Frame: Baseline through 24 hours post Day 28 dose]

Part C Cohort 1: change in weight over time [Time Frame: Baseline through Day 49]

SAD: area under the concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) of single oral dose [Time Frame: Baseline through 72 hours post dose]

Part B and Part C Cohorts 2 and 3: Cmax of multiple oral doses [Time Frame: Baseline through 24 hours post Day 28 dose]

SAD: apparent terminal half-life (t1/2) of single oral dose [Time Frame: Baseline through 72 hours post dose]

Part C Cohort 1: t1/2 of multiple oral doses [Time Frame: Baseline through Day 42]

Secondary ID(s)

PTI-428-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors