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

NCT03500263 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PTI-808-02
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 4

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability measured by the number of subjects who experience adverse events and potentially significant clinical laboratory assessments, electrocardiography, physical examinations, vital signs.

  Baseline through Day 21

Secondary Outcomes (4)

• Apparent terminal half-life (t1/2) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)

  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)

  Day 1 through 15

• Maximum plasma concentration (Cmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)

  Day 1 through 15

• Change in FEV1 over time

  Baseline through Day 21

Other Outcomes (6)

• Change in sweat chloride over time

  Baseline through Day 21

• Change in weight over time

  Baseline through Day 21

• Change in BMI over time

  Baseline through Day 21

Study Arms (6)

Cohorts 1 and 2: PTI-808 Active Co-admin with PTI-801 Active

ACTIVE COMPARATOR

Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.

Drug: PTI-808; Drug: PTI-801

Cohorts 1 and 2: PTI-808 Placebo Co-admin with PTI-801 Placebo

PLACEBO COMPARATOR

Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.

Drug: Placebo

Cohort 3 PTI-808 Active + PTI-801 Active + PTI-428 Active

ACTIVE COMPARATOR

Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.

Drug: PTI-808; Drug: PTI-801; Drug: PTI-428

Cohort 3 PTI-808 placebo + PTI-801 Placebo + PTI-428 Placebo

PLACEBO COMPARATOR

Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.

Drug: Placebo

Cohort 4 PTI-808 Active + PTI-801 Active + PTI-428 Active

ACTIVE COMPARATOR

Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for 7 days immediately followed by PTI-808 co-administered with PTI-801 or placebos once-a-day for 7 days. A follow-up visit will occur on Day 21.

Drug: PTI-808; Drug: PTI-801; Drug: PTI-428

Cohort 4 PTI-808 Placebo + PTI-801 Placebo + PTI-428 Placebo

PLACEBO COMPARATOR

Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for 7 days immediately followed by PTI-808 co-administered with PTI-801 or placebos once-a-day for 7 days. A follow-up visit will occur on Day 21.

Drug: Placebo

Interventions

PTI-808 DRUG

Active

Cohort 3 PTI-808 Active + PTI-801 Active + PTI-428 Active; Cohort 4 PTI-808 Active + PTI-801 Active + PTI-428 Active; Cohorts 1 and 2: PTI-808 Active Co-admin with PTI-801 Active

Placebo DRUG

Placebo

Cohort 3 PTI-808 placebo + PTI-801 Placebo + PTI-428 Placebo; Cohort 4 PTI-808 Placebo + PTI-801 Placebo + PTI-428 Placebo; Cohorts 1 and 2: PTI-808 Placebo Co-admin with PTI-801 Placebo

PTI-801 DRUG

Active

Cohort 3 PTI-808 Active + PTI-801 Active + PTI-428 Active; Cohort 4 PTI-808 Active + PTI-801 Active + PTI-428 Active; Cohorts 1 and 2: PTI-808 Active Co-admin with PTI-801 Active

PTI-428 DRUG

Active

Cohort 3 PTI-808 Active + PTI-801 Active + PTI-428 Active; Cohort 4 PTI-808 Active + PTI-801 Active + PTI-428 Active

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Proteostasis Therapeutics, Inc.: lead

Study Sites (4)

Celerion

Belfast, BT9 6AD, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, G514TF, United Kingdom

Location

Medicines Evaluation Unit

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2018
• First Posted: April 18, 2018
• Study Start: January 30, 2018
• Primary Completion: March 13, 2019
• Study Completion: March 13, 2019
• Last Updated: April 6, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share

Locations

GB (4)