Study Designed to Assess the Safety, Tolerability and PK of PTI-808 in Healthy Volunteers and in Adults With Cystic Fibrosis

A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PTI-808 in Healthy Adult Subjects and in Adults With Cystic Fibrosis

Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD), multiple ascending dose (MAD), and Food Effect (FE) treatment groups.

The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and will be followed for 7 days post dose. A safety review committee (SRC) will convene after the completion of each cohort to evaluate safety and pharmacokinetic (PK) data.

Following the conclusion of the respective SAD level dose groups and after sufficient review of study data and approval by the SRC, a second set of healthy adult subjects will participate in an assigned MAD treatment group. The MAD treatment group is comprised of 3 ascending dose level cohorts where subjects will be randomized to receive either PTI-808 or placebo daily for 7 days and will be followed for 7 days after receiving the last dose.

Also following the conclusion of the respective SAD level dose groups, healthy adult subjects will participate in the FE treatment group.

Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive days.

Part 3 will enroll adult subjects with cystic fibrosis (CF) into a MAD treatment group consisting of 2 cohorts. Subjects will receive PTI-808 co-administered with PTI-801 and PTI-428. PTI-808 will be administered daily for 7 consecutive days followed by PTI-808 + PTI-801 + PTI-428 administered daily for 14 consecutive days.

Part 4 will enroll adult subjects with cystic fibrosis (CF) into 28-day cohorts. Subjects will receive PTI-808 co-administered with PTI-801 with or without PTI-428 versus matching placebo.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer - Complete; Cystic Fibrosis - Complete
• Intervention / Treatment: Drug: Placebo; Drug: PTI-801; Drug: PTI-808; Drug: PTI-428

Detailed Description

Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD), multiple ascending dose (MAD), and Food Effect (FE) treatment groups.

The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and will be followed for 7 days post dose.

The MAD treatment group is comprised of 3 ascending dose level cohorts where subjects will be randomized to receive either PTI-808 or placebo daily for 7 days and will be followed for 7 days after receiving the last dose.

Following the conclusion of the respective SAD level dose groups the food effect portion of the study will be initiated and subjects will be randomized to receive an initial single dose of PTI-808 either after an overnight fast of at least 10 hours (fasted group) or after an overnight fast of at least 10 hours followed the consumption of a high fat high calorie meal (fed group). After a 10 day washout period, subjects will cross over to the opposite group and receive a second dose of PTI-808. Subjects will be followed for up to 7 days following dosing.

Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive days.

Part 3 - Part 3 will enroll adult subjects with CF to assess the safety, tolerability, and PK of multiple ascending doses of PTI-808 co-administered with PTI-801 and PTI-428. Subjects will receive 7 days of PTI-808 or placebo followed by 14 days of PTI-808 or placebo co-administered with PTI-801+PTI-428 or matching placebos.

Part 4 - Part 4 will assess the safety, tolerability, PK, and the effects of PTI-808 co-administered with PTI-801 with or without PTI-428 over a 28-day treatment period in CF subjects who are either homozygous for the F508del CFTR genotype or are heterozygous for the F508del CFTR genotype. Subjects will be randomized to receive treatment with PTI-808 co-administered with PTI-801 with or without PTI-428 versus matching placebo.

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Lambton, New South Wales, Australia, 2305
      • John Hunter Hospital
• Belgium
  • Brussels, Belgium, 1090
    • Universitair Ziekenhuis Brussel
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • Québec, Canada, G1V4G5
    • Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z1Y6
      • St. Paul's Hospital
  • Quebec
    • Montréal, Quebec, Canada, H4A3J1
      • McGill University Health Centre
    • Montréal, Quebec, Canada, H2X3E4
      • Centre Hospitalier de l'Université de Montréal (CHUM)
• Denmark
  • Copenhagen, Denmark, 2100
    • University of Copenhagen Rigshospitalet
• France
  • Lyon, France, 69495
    • Hospices Civils de Lyon
  • Paris, France, 75014
    • Hôpital Cochin
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06001
      • Hôpital Pasteur
  • Gironde
    • Pessac, Gironde, France, 33600
      • Hôpital Haut Lévêque
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44093
      • Hôpital Guillaume-et-René-Laennec
  • Marne
    • Reims, Marne, France, 51092
      • Hôpital Maison Blanche Maladies respiratoires et allergologie
• Germany
  • Berlin, Germany, 10117
    • Charité Universitätsmedizin Berlin
  • Cologne, Germany, 50937
    • University Hospital Cologne
  • Essen, Germany, 45239
    • Universitätsklinikum Essen
  • Frankfurt, Germany, 60590
    • Klinikum der J.W. Goethe Universität
  • München, Germany, 81377
    • Klinikum des Universität München
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Auckland Clinical Studies Ltd.
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Belfast City Hospital
  • London, United Kingdom, SE59RS
    • King's College Hospital
  • Southampton, United Kingdom, SO16 6YD
    • University Hospital Southampton
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Royal Devon and Exeter Hospital
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH42XU
      • Western General Hospital
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B9 5SS
      • Birmingham Heartlands Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Banner University of Arizona Medical Center
  • California
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Altamonte Springs, Florida, United States, 32803
      • Central Florida Pulmonary Group
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Children's Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine, University of Michigan
    • Detroit, Michigan, United States, 48201
      • Harper University Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • University of North Carolina at Chapel Hill
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • San Antonio, Texas, United States, 78209
      • ICON Early Phase Services
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Part 1 and Part 2 Inclusion Criteria:

1. Adults aged 18 to 55 years old, inclusive, at the time of informed consent
2. Body mass index ≥18 and <30 kg/m2
3. Subject must be a non-smoker and non-tobacco user for a minimum of 30 days prior to screening and for the duration of the study.
4. Subject understands the full nature and purpose of the study, including possible risks and side effects, and is willing and able to comply with all compulsory study procedures and provides informed consent/permission prior to any study procedures being performed.
5. Females of childbearing potential and males capable of fathering a child must meet the contraception requirements

Part 1 & Part 2 Exclusion Criteria:

1. History or current evidence of any clinically significant cardiac, endocrinologic, hematologic, hepatobiliary, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease, as determined by the investigator
2. Prolonged QT interval with Fridericia's correction >450 msec at screening
3. Abnormal liver function as defined by aspartate transaminase (AST), alanine transaminase (ALT), or bilirubin >1.5× the upper limit of the normal range
4. Abnormal renal function at screening defined as creatinine clearance <90 mL/min using the Cockroft-Gault equation
5. Clinically significant screening results that would exclude subject from the study (e.g., medical histories, PE, ECGs, vital signs, and laboratory profiles) as deemed by the investigator
6. Participation in another clinical study or treatment with an investigational agent within 30 days or five half-lives, whichever is longer, prior to Study Day 1
7. History of cancer within the past 5 years (excluding non-melanoma skin cancer)
8. History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator
9. Positive urine screen for prohibited drugs (cocaine, cannabinoids, nicotine [urine cotinine is the detection mechanism for nicotine], opiates, barbiturates, amphetamines, and benzodiazepines) or positive alcohol test at screening
10. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCVAb)
11. Clinically significant infection within 3 months of screening as determined by the investigator
12. Known or suspected hypersensitivity or idiosyncratic reaction to study medication or any components thereof
13. Has donated blood within 3 months of screening or plans to donate blood within 3 months of study completion
14. Pregnant or nursing women
15. Any conditions that, in the opinion of the investigator, would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study
16. Use of prohibited medications within 14 days prior to dosing of study drug

Part 3 CF Inclusion Criteria:

1. Confirmed diagnosis of CF with the F508del/F508del genotype
2. Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive
3. Non-smoker and non-tobacco user for a minimum of 30 days prior to screening

Part 3 CF Exclusion Criteria:

1. 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
2. History of cancer within the past 5 years (excluding cervical cancer in situ with curative therapy for at least one year prior to screening and non-melanoma skin cancer)
3. History of organ transplantation
4. 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
5. 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
6. History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator
7. Pregnant or nursing women
8. Currently taking or has taken a CFTR modulator within 30 days prior to initial dose of study drugs

Part 4 CF Inclusion Criteria:

1. Confirmed diagnosis of CF with either the F508del CFTR homozygous genotype on record or for heterozygote subjects, only one copy of the F508del CFTR mutation on record
2. Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive
3. Non-smoker and non-tobacco user for a minimum of 30 days prior to screening

Part 4 CF Exclusion Criteria:

1. 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
2. History of cancer within the past 5 years (excluding cervical cancer in situ with curative therapy for at least one year prior to screening and non-melanoma skin cancer)
3. History of organ transplantation
4. 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 28 days of Day 1
5. 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 of Day 1
6. History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator
7. Pregnant or nursing women
8. Currently taking or has taken a CFTR modulator within 14 days prior to the screening visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

15

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SAD PTI-808 Active; Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.	Drug: PTI-808; Active
Placebo Comparator: SAD PTI-808 Placebo; Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.	Drug: Placebo; Placebo
Active Comparator: MAD PTI-808 Active; Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.	Drug: PTI-808; Active
Placebo Comparator: MAD PTI-808 Placebo; Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.	Drug: Placebo; Placebo
Active Comparator: FE PTI-808 Active; Subjects will be randomized to Fed or Fasted on Days 1 and 12. Follow up visits will occur 7 days post Day 12 dose.	Drug: PTI-808; Active
Placebo Comparator: FE PTI-808 Placebo; Subjects will be randomized to Fed or Fasted on Days 1 and 12. Follow up visits will occur 7 days post Day 12 dose.	Drug: Placebo; Placebo
Experimental: Part 2 PTI-808 + PTI-801 + PTI-428 Active; One cohort is planned where subjects will be randomized to either the triple active arm (dosed with PTI 808+PTI 801+PTI 428) OR placebo arm.	Drug: PTI-801; Active; Drug: PTI-808; Active; Drug: PTI-428; Active
Placebo Comparator: Part 2 matching Placebos; In all three cohorts in part 2, subjects will be randomized to active drug or placebo. The placebo arm for all cohorts consists of placebo capsules matching PTI-808+PTI-801+PTI-428.	Drug: Placebo; Placebo
Experimental: Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo; One cohort is planned where subjects are randomized to either 808 placebo + dual active arm (dosed with placebo matching PTI 808 plus PTI 801 + PTI 428) OR placebo arm.	Drug: Placebo; Placebo; Drug: PTI-801; Active; Drug: PTI-428; Active
Active Comparator: Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo; One cohort is planned where subjects are randomized to either 428 placebo + dual active arm (dosed with placebo matching PTI 428 plus PTI 808 and PTI 801) OR placebo arm.	Drug: Placebo; Placebo; Drug: PTI-801; Active; Drug: PTI-808; Active
Active Comparator: Part 3 CF MAD PTI-808 + PTI-801 + PTI-428; In all cohorts in Part 3, subjects will be will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28.	Drug: PTI-801; Active; Drug: PTI-808; Active; Drug: PTI-428; Active
Placebo Comparator: Part 3 CF MAD PTI-808 placebo+PTI-801 placebo+PTI-428 placebo; In all cohorts in Part 3, subjects will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28.	Drug: Placebo; Placebo
Active Comparator: Part 4 CF PTI-808 + PTI-801 + PTI-428; In cohorts 3 & 4 subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42.	Drug: PTI-801; Active; Drug: PTI-808; Active; Drug: PTI-428; Active
Active Comparator: Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo; In cohorts 3 & 4, subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42.	Drug: PTI-801; Active; Drug: PTI-808; Active
Placebo Comparator: Part 4 CF PTI-808 placebo + PTI-801 placebo + PTI-428 placebo; In cohorts 3 & 4, subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 SAD and MAD: Adverse Events	Safety and tolerability measure by number of subjects who experience adverse events	Baseline to up to 14 days
Part 1 SAD and MAD: Physical Exams	Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations	Baseline to up to 14 days
Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in vital signs	Safety and tolerability measure by number of subjects who experience potential clinically significant changes in vital signs	Baseline to up to 14 days
Part 1 SAD and MAD: ECGs	Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs	Baseline to up to 14 days
Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in safety labs	Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs	Baseline to up to 14 days
Part 1 SAD and FE: terminal half life	Apparent terminal half-life (t1/2) of single oral dose	Through 72 hours post dose
Part 1 SAD and FE : Tmax	Time to reach maximum plasma concentration (Tmax) of single oral dose	Through 72 hours post dose
Part 1 SAD and FE: Cmax	Maximum plasma concentration (Cmax) of single oral dose	Through 72 hours post dose
Part 1 SAD : AUC	Area under the concentration-time curve from time 0 to 24 hours post dose (AUC 0-24) of single oral dose	Through 24 hours post dose
Part 1 SAD and FE: AUC0	AUC from time 0 to time of last measurable concentration (AUC0-last) of single oral dose	Through 72 hours post dose
Part 1 SAD and FE: AUC0-inf	AUC from time 0 to infinity (AUC0-inf) of single dose	Through 72 hours post dose
Part 1 MAD: t1/2	t1/2 of multiple oral dose	Through 72 hours post dose
Part 1 MAD: Tmax	Tmax of multiple oral doses	Through 72 hours post dose
Part 1 MAD: Cmax	Cmax of multiple oral doses	Through 72 hours post last dose
Part 1 MAD: AUC0-24	AUC0-24 of multiple oral dose	Through 24 hours post last dose
Part 1 MAD: AUC0-last	AUC0-last of multiple oral doses	Through 72 hours post last dose
Part 1 MAD: Urine	Cumulative amount of PTI-808 excreted unchanged in urine (Ae) as appropriate of multiple oral doses	Through 24 hours post last dose
Part 1 MAD: CLR	Renal clearance (CLR) of multiple oral doses	Through 24 hours post dose
Part 2: Physical Exams	Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations	Baseline up to 14 days
Part 2: ECGs	Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs	Baseline up to 14 days
Part 2: Safety Labs	Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs	Baseline up to 14 days
Part 2: Vitals Signs	Measure by number of subjects who experience potential clinically significant changes in vital signs	Baseline up to 14 days
Part 3 CF: Physical Exams	Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations	Baseline up to 28 days
Part 3 CF: ECGs	Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs	Baseline up to 28 days
Part 3 CF: Safety Labs	Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs	Baseline up to 28 days
Part 3 CF: Vital Signs	Measured by number of subjects who experience potential clinically significant changes in vital signs	Baseline up to 28 days
Part 4 CF: Physical Exams	Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations	Baseline up to 42 days
Part 4 CF: ECGs	Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs	Baseline up to 42 days
Part 4 CF: Safety Labs	Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs	Baseline up to 42 days
Part 4 CF: Vital Signs	Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations	Baseline up to 42 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Apparent terminal half life (t1/2) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428	Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults	Day 1 through Day 10
Part 2: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428	Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults	Day 1 through Day 10
Part 2: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428	Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults	Day 1 through Day 10
Part 2: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428	Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults	Day 1 through Day 10
Part 2: AUC from time 0 to infinity (AUC0-inf) of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428	Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults	Day 1 through Day 10
Part 3 CF: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428	Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF	Day 1 through Day 22
Part 3 CF: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428	Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF	Day 1 through Day 22
Part 3 CF: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428	Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF	Day 1 through Day 22
Part 3 CF: FEV1	Change in forced expiratory volume in one second (FEV1) over time	Baseline through Day 28
Part 4 CF: Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428	Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or with out PTI 428 in adults with CF	Day 1 through Day 28
Part 4 CF: Maximum plasma concentration (Cmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428	Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or with out PTI 428 in adults with CF	Day 1 through 28
Part 4 CF: AUC0-last of multiple oral doses when PTI 808 + PTI 801 is coadministered with or without PTI 428 in adults with CF	Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or without PTI 428 in adults with CF	Day 1 through 28
Part 4 CF: FEV1	Change in forced expiratory volume in one second (FEV1) over time	Baseline through Day 42
Part 4 CF Sweat Chloride	Change in sweat chloride concentrations over time	Baseline through Day 42

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2 Nasal biomarker	change in nasal epithelial mRNA and protein over time	Baseline up to 14 days
Part 3 CF Sweat Chloride	Change in sweat chloride concentrations over time	Baseline up to 28 days
Part 3 CF Nasal biomarker	Change in nasal epithelial mRNA and protein expression over time	Baseline up to 28 days
Part 4 CF Weight and BMI	Change in weight and BMI over time	Baseline up to 42 days
Part 4 CF Blood Glucose	Change in blood glucose over time	Baseline up to 42 days
Part 4 CF disease-specific health related quality of life	Change in disease-specific health related quality of life over time	Baseline up to 42 days
Part 4 CF Nasal biomarker	Change in nasal epithelial mRNA and protein expression over time	Baseline up to 42 days

Collaborators and Investigators

• Sponsor: Proteostasis Therapeutics, Inc.
• Investigators: Principal Investigator: Cassandra Key, MD, ICON Early Phase Services (Parts 1 & 2); Principal Investigator: Patrick Flume, MD, Medical University of South Carolina (Parts 3 & 4)

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2017
• Primary Completion (Actual): December 23, 2019
• Study Completion (Actual): December 23, 2019

Study Registration Dates

• First Submitted: August 7, 2017
• First Submitted That Met QC Criteria: August 11, 2017
• First Posted (Actual): August 16, 2017

Study Record Updates

• Last Update Posted (Actual): April 22, 2020
• Last Update Submitted That Met QC Criteria: April 20, 2020
• Last Verified: April 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-808-01

Drug and device information, study documents

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