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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03251092
• Date of registration: 07/08/2017
• Prospective Registration: No
• Primary sponsor: Proteostasis Therapeutics, Inc.
• Public title: Study Designed to Assess the Safety, Tolerability and PK of PTI-808 in Healthy Volunteers and in Adults With Cystic Fibrosis
• Scientific title: 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
• Date of first enrolment: July 17, 2017
• Target sample size: 179
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03251092
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 1/Phase 2

Countries of recruitment

Australia, Belgium, Canada, Denmark, France, Germany, New Zealand, United Kingdom, United States

Contacts

• Name: Cassandra Key, MD
• Affiliation: ICON Early Phase Services (Parts 1 & 2)

• Name: Patrick Flume, MD
• Affiliation: Medical University of South Carolina (Parts 3 & 4)

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: 99 Years
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis - Complete

Healthy Volunteer - Complete

Intervention(s)

Drug: PTI-428

Drug: PTI-808

Drug: Placebo

Drug: PTI-801

Primary Outcome(s)

Part 2: Safety Labs [Time Frame: Baseline up to 14 days]

Part 3 CF: ECGs [Time Frame: Baseline up to 28 days]

Part 4 CF: Safety Labs [Time Frame: Baseline up to 42 days]

Part 1 MAD: AUC0-last [Time Frame: Through 72 hours post last dose]

Part 1 MAD: Urine [Time Frame: Through 24 hours post last dose]

Part 2: ECGs [Time Frame: Baseline up to 14 days]

Part 2: Physical Exams [Time Frame: Baseline up to 14 days]

Part 4 CF: ECGs [Time Frame: Baseline up to 42 days]

Part 1 MAD: Cmax [Time Frame: Through 72 hours post last dose]

Part 1 SAD and FE: AUC0 [Time Frame: Through 72 hours post dose]

Part 1 SAD and FE: terminal half life [Time Frame: Through 72 hours post dose]

Part 2: Vitals Signs [Time Frame: Baseline up to 14 days]

Part 1 SAD and FE : Tmax [Time Frame: Through 72 hours post dose]

Part 1 SAD and MAD: Physical Exams [Time Frame: Baseline to up to 14 days]

Part 4 CF: Physical Exams [Time Frame: Baseline up to 42 days]

Part 1 MAD: AUC0-24 [Time Frame: Through 24 hours post last dose]

Part 1 MAD: CLR [Time Frame: Through 24 hours post dose]

Part 1 MAD: Tmax [Time Frame: Through 72 hours post dose]

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]

Part 1 MAD: t1/2 [Time Frame: Through 72 hours post dose]

Part 1 SAD : AUC [Time Frame: Through 24 hours post dose]

Part 1 SAD and FE: AUC0-inf [Time Frame: Through 72 hours post dose]

Part 1 SAD and MAD: ECGs [Time Frame: Baseline to up to 14 days]

Part 3 CF: Physical Exams [Time Frame: Baseline up to 28 days]

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]

Part 1 SAD and FE: Cmax [Time Frame: Through 72 hours post dose]

Part 1 SAD and MAD: Adverse Events [Time Frame: Baseline to up to 14 days]

Part 3 CF: Safety Labs [Time Frame: Baseline up to 28 days]

Part 3 CF: Vital Signs [Time Frame: Baseline up to 28 days]

Part 4 CF: Vital Signs [Time Frame: Baseline up to 42 days]

Secondary Outcome(s)

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]

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]

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]

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]

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]

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]

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]

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]

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]

Part 3 CF: FEV1 [Time Frame: Baseline through Day 28]

Part 4 CF: FEV1 [Time Frame: Baseline through Day 42]

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]

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]

Part 4 CF Sweat Chloride [Time Frame: Baseline through Day 42]

Secondary ID(s)

PTI-808-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors