Clinical trial NCT03500263: Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Proteostasis Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-04-18
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is a randomized, double-blind, placebo-controlled, study that will be conducted at multiple centers in subjects with Cystic Fibrosis (CF) who are either homozygous for the F508del mutation or heterozygous with at least copy of the F508del mutation.

Detailed description: Study PTI-808-02 will enroll up to approximately 32 subjects. Subjects in the first cohort will receive PTI-808 and PTI-801. Following completion of Cohort 1, initiation of enrollment into subsequent cohorts will be based upon review and approval by the Safety Review Committee (SRC).

Eligibility 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

Primary outcomes:
measure: Safety and tolerability measured by the number of subjects who experience adverse events and potentially significant clinical laboratory assessments, electrocardiography, physical examinations, vital signs.
timeFrame: Baseline through Day 21
Secondary outcomes:
measure: Apparent terminal half-life (t1/2) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)
timeFrame: Day 1 through 15
measure: Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)
timeFrame: Day 1 through 15
measure: Maximum plasma concentration (Cmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)
timeFrame: Day 1 through 15
measure: Change in FEV1 over time
timeFrame: Baseline through Day 21
Other outcomes:
measure: Change in sweat chloride over time
timeFrame: Baseline through Day 21
measure: Change in weight over time
timeFrame: Baseline through Day 21
measure: Change in BMI over time
timeFrame: Baseline through Day 21
measure: Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain results over time
timeFrame: Baseline through Day 21
measure: Change in nasal epithelial mRNA expression over time
timeFrame: Baseline through Day 21
measure: Change in nasal protein expression over time
timeFrame: Baseline through Day 21
Locations:
city: Belfast
country: United Kingdom
facility: Celerion
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit
Study officials:
References: