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

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ClinicalTrials.gov Identifier: NCT03251092
Recruitment Status : Recruiting
First Posted : August 16, 2017
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Proteostasis Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE August 7, 2017
First Posted Date  ICMJE August 16, 2017
Last Update Posted Date September 17, 2019
Actual Study Start Date  ICMJE July 17, 2017
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
  • Part 1 SAD and MAD: Adverse Events [ Time Frame: Baseline to up to 14 days ]
    Safety and tolerability measure by number of subjects who experience adverse events
  • Part 1 SAD and MAD: Physical Exams [ Time Frame: Baseline to up to 14 days ]
    Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations
  • Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in vital signs [ Time Frame: Baseline to up to 14 days ]
    Safety and tolerability measure by number of subjects who experience potential clinically significant changes in vital signs
  • Part 1 SAD and MAD: ECGs [ Time Frame: Baseline to up to 14 days ]
    Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs
  • Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in safety labs [ Time Frame: Baseline to up to 14 days ]
    Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs
  • Part 1 SAD and FE: terminal half life [ Time Frame: Through 72 hours post dose ]
    Apparent terminal half-life (t1/2) of single oral dose
  • Part 1 SAD and FE : Tmax [ Time Frame: Through 72 hours post dose ]
    Time to reach maximum plasma concentration (Tmax) of single oral dose
  • Part 1 SAD and FE: Cmax [ Time Frame: Through 72 hours post dose ]
    Maximum plasma concentration (Cmax) of single oral dose
  • Part 1 SAD : AUC [ Time Frame: Through 24 hours post dose ]
    Area under the concentration-time curve from time 0 to 24 hours post dose (AUC 0-24) of single oral dose
  • Part 1 SAD and FE: AUC0 [ Time Frame: Through 72 hours post dose ]
    AUC from time 0 to time of last measurable concentration (AUC0-last) of single oral dose
  • Part 1 SAD and FE: AUC0-inf [ Time Frame: Through 72 hours post dose ]
    AUC from time 0 to infinity (AUC0-inf) of single dose
  • Part 1 MAD: t1/2 [ Time Frame: Through 72 hours post dose ]
    t1/2 of multiple oral dose
  • Part 1 MAD: Tmax [ Time Frame: Through 72 hours post dose ]
    Tmax of multiple oral doses
  • Part 1 MAD: Cmax [ Time Frame: Through 72 hours post last dose ]
    Cmax of multiple oral doses
  • Part 1 MAD: AUC0-24 [ Time Frame: Through 24 hours post last dose ]
    AUC0-24 of multiple oral dose
  • Part 1 MAD: AUC0-last [ Time Frame: Through 72 hours post last dose ]
    AUC0-last of multiple oral doses
  • Part 1 MAD: Urine [ Time Frame: Through 24 hours post last dose ]
    Cumulative amount of PTI-808 excreted unchanged in urine (Ae) as appropriate of multiple oral doses
  • Part 1 MAD: CLR [ Time Frame: Through 24 hours post dose ]
    Renal clearance (CLR) of multiple oral doses
  • Part 2: Physical Exams [ Time Frame: Baseline up to 14 days ]
    Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations
  • Part 2: ECGs [ Time Frame: Baseline up to 14 days ]
    Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs
  • Part 2: Safety Labs [ Time Frame: Baseline up to 14 days ]
    Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs
  • Part 2: Vitals Signs [ Time Frame: Baseline up to 14 days ]
    Measure by number of subjects who experience potential clinically significant changes in vital signs
  • Part 3 CF: Physical Exams [ Time Frame: Baseline up to 28 days ]
    Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
  • Part 3 CF: ECGs [ Time Frame: Baseline up to 28 days ]
    Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs
  • Part 3 CF: Safety Labs [ Time Frame: Baseline up to 28 days ]
    Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs
  • Part 3 CF: Vital Signs [ Time Frame: Baseline up to 28 days ]
    Measured by number of subjects who experience potential clinically significant changes in vital signs
  • Part 4 CF: Physical Exams [ Time Frame: Baseline up to 42 days ]
    Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
  • Part 4 CF: ECGs [ Time Frame: Baseline up to 42 days ]
    Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs
  • Part 4 CF: Safety Labs [ Time Frame: Baseline up to 42 days ]
    Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs
  • Part 4 CF: Vital Signs [ Time Frame: Baseline up to 42 days ]
    Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
Original Primary Outcome Measures  ICMJE
 (submitted: August 11, 2017)
  • Part 1 SAD and MAD: [ Time Frame: Baseline to up to 14 days ]
    Safety and tolerability measure by number of subjects who experience adverse events and potential clinically significant changes in safety labs, ECGs, physical examinations and vital signs
  • Part 1 SAD and FE: [ Time Frame: Through 72 hours post dose ]
    Apparent terminal half-life (t1/2) of single oral dose
  • Part 1 SAD and FE: [ Time Frame: Through 72 hours post dose ]
    Time to reach maximum plasma concentration (Tmax) of single oral dose
  • Part 1 SAD and FE: [ Time Frame: Through 72 hours post dose ]
    Maximum plasma concentration (Cmax) of single oral dose
  • Part 1 SAD: [ Time Frame: Through 24 hours post dose ]
    Area under the concentration-time curve from time 0 to 24 hours post dose (AUC 0-24) of single oral dose
  • Part 1 SAD and FE: [ Time Frame: Through 72 hours post dose ]
    AUC from time 0 to time of last measurable concentration (AUC0-last) of single oral dose
  • Part 1 SAD and FE: [ Time Frame: Through 72 hours post dose ]
    AUC from time 0 to infinity (AUC0-inf) of single dose
  • Part 1 MAD: [ Time Frame: Through 72 hours post dose ]
    t1/2 of multiple oral dose
  • MAD: [ Time Frame: Through 72 hours post dose ]
    Tmax of multiple oral doses
  • Part 1 MAD: [ Time Frame: Through 72 hours post last dose ]
    Cmax of multiple oral doses
  • Part 1 MAD: [ Time Frame: Through 24 hours post last dose ]
    AUC0-24 of multiple oral dose
  • Part 1 MAD: [ Time Frame: Through 72 hours post last dose ]
    AUC0-last of multiple oral doses
  • Part 1 MAD: [ Time Frame: Through 24 hours post last dose ]
    Cumulative amount of PTI-808 excreted unchanged in urine (Ae) as appropriate of multiple oral doses
  • Part 1 MAD: [ Time Frame: Through 24 hours post dose ]
    Renal clearance (CLR) of multiple oral doses
Change History Complete list of historical versions of study NCT03251092 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
  • Part 2: Apparent terminal half life (t1/2) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428 [ Time Frame: Day 1 through Day 10 ]
    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
  • Part 2: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428 [ Time Frame: Day 1 through Day 10 ]
    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
  • Part 2: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428 [ Time Frame: Day 1 through Day 10 ]
    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
  • Part 2: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428 [ Time Frame: Day 1 through Day 10 ]
    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
  • 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 [ Time Frame: Day 1 through Day 10 ]
    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
  • 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 [ Time Frame: Day 1 through Day 22 ]
    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
  • Part 3 CF: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428 [ Time Frame: Day 1 through Day 22 ]
    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
  • Part 3 CF: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428 [ Time Frame: Day 1 through Day 22 ]
    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
  • Part 3 CF: FEV1 [ Time Frame: Baseline through Day 28 ]
    Change in forced expiratory volume in one second (FEV1) over time
  • 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 [ Time Frame: Day 1 through Day 28 ]
    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
  • Part 4 CF: Maximum plasma concentration (Cmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428 [ Time Frame: Day 1 through 28 ]
    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
  • 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 [ Time Frame: Day 1 through 28 ]
    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
  • Part 4 CF: FEV1 [ Time Frame: Baseline through Day 42 ]
    Change in forced expiratory volume in one second (FEV1) over time
  • Part 4 CF Sweat Chloride [ Time Frame: Baseline through Day 42 ]
    Change in sweat chloride concentrations over time
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: June 14, 2019)
  • Part 2 Nasal biomarker [ Time Frame: Baseline up to 14 days ]
    change in nasal epithelial mRNA and protein over time
  • Part 3 CF Sweat Chloride [ Time Frame: Baseline up to 28 days ]
    Change in sweat chloride concentrations over time
  • Part 3 CF Nasal biomarker [ Time Frame: Baseline up to 28 days ]
    Change in nasal epithelial mRNA and protein expression over time
  • Part 4 CF Weight and BMI [ Time Frame: Baseline up to 42 days ]
    Change in weight and BMI over time
  • Part 4 CF Blood Glucose [ Time Frame: Baseline up to 42 days ]
    Change in blood glucose over time
  • Part 4 CF disease-specific health related quality of life [ Time Frame: Baseline up to 42 days ]
    Change in disease-specific health related quality of life over time
  • Part 4 CF Nasal biomarker [ Time Frame: Baseline up to 42 days ]
    Change in nasal epithelial mRNA and protein expression over time
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Designed to Assess the Safety, Tolerability and PK of PTI-808 in Healthy Volunteers and in Adults With Cystic Fibrosis
Official Title  ICMJE 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
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Healthy Volunteer - Complete
  • Cystic Fibrosis
Intervention  ICMJE
  • Drug: PTI-808
    Active
  • Drug: Placebo
    Placebo
  • Drug: PTI-428
    Active
  • Drug: PTI-801
    Active
Study Arms  ICMJE
  • Active Comparator: SAD PTI-808 Active
    Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.
    Intervention: Drug: PTI-808
  • Placebo Comparator: SAD PTI-808 Placebo
    Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.
    Intervention: Drug: 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.
    Intervention: Drug: PTI-808
  • Placebo Comparator: MAD PTI-808 Placebo
    Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.
    Intervention: Drug: 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.
    Intervention: Drug: PTI-808
  • 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.
    Intervention: Drug: 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.
    Interventions:
    • Drug: PTI-808
    • Drug: PTI-428
    • Drug: PTI-801
  • 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.
    Intervention: Drug: 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.
    Interventions:
    • Drug: Placebo
    • Drug: PTI-428
    • Drug: PTI-801
  • 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.
    Interventions:
    • Drug: PTI-808
    • Drug: Placebo
    • Drug: PTI-801
  • 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.
    Interventions:
    • Drug: PTI-808
    • Drug: PTI-428
    • Drug: PTI-801
  • 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.
    Intervention: Drug: 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.
    Interventions:
    • Drug: PTI-808
    • Drug: PTI-428
    • Drug: PTI-801
  • 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.
    Interventions:
    • Drug: PTI-808
    • Drug: PTI-801
  • 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.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 14, 2019)
180
Original Estimated Enrollment  ICMJE
 (submitted: August 11, 2017)
60
Estimated Study Completion Date  ICMJE January 2020
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Proteostasis Clinical Trials 1-866-223-3262 pticlinicaltrials@proteostasis.com
Listed Location Countries  ICMJE Belgium,   Canada,   Denmark,   France,   Germany,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03251092
Other Study ID Numbers  ICMJE PTI-808-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Proteostasis Therapeutics, Inc.
Study Sponsor  ICMJE Proteostasis Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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)
PRS Account Proteostasis Therapeutics, Inc.
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP