Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03500263
• Date of registration: 09/04/2018
• Prospective Registration: No
• Primary sponsor: Proteostasis Therapeutics, Inc.
• Public title: Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis
• Scientific title: A Phase 1 / 2, Randomized, Double-Blind, Placebo-Controlled Study Designed to Evaluate the Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis
• Date of first enrolment: January 30, 2018
• Target sample size: 12
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03500263
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 1/Phase 2

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

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



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

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: PTI-808

Drug: PTI-428

Drug: Placebo

Drug: PTI-801

Primary Outcome(s)

Safety and tolerability measured by the number of subjects who experience adverse events and potentially significant clinical laboratory assessments, electrocardiography, physical examinations, vital signs. [Time Frame: Baseline through Day 21]

Secondary Outcome(s)

Change in FEV1 over time [Time Frame: Baseline through Day 21]

Apparent terminal half-life (t1/2) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only) [Time Frame: Day 1 through 15]

Maximum plasma concentration (Cmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only) [Time Frame: Day 1 through 15]

Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only) [Time Frame: Day 1 through 15]

Secondary ID(s)

PTI-808-02

Source(s) of Monetary Support

Please refer to primary and secondary sponsors