Study Assessing the Safety, Tolerability, Pharmacokinetics, Food Effect, and Drug-Drug Interactions of PTI-801 in Healthy Volunteers, and Safety, Tolerability, and Pharmacokinetics of PTI-801 in Subjects With Cystic Fibrosis
NCT ID: NCT03140527
Last Updated: 2020-04-30
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
171 participants
INTERVENTIONAL
2017-04-10
2020-02-27
Brief Summary
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Part 2 Cohorts 1 through 3 will enroll adult subjects with cystic fibrosis (CF) currently on stable ivacaftor/lumacaftor background therapy for a minimum of three months. Part 2 Cohorts 4 and Cohort 5 will enroll adult subjects with CF not currently receiving cystic fibrosis conductance regulator (CFTR) modulator therapy within 30 days prior to Day 1. Part 2 Cohort 6 will enroll adult subjects with cystic fibrosis on stable tezacaftor/ivacaftor background therapy. Approximately 104 subjects will be enrolled in Part 2.
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Detailed Description
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PART 2 Part 2 is comprised of a MAD treatment group with three cohorts, a co-administration group with two cohorts and a treatment group with one cohort.
Following the conclusion of the complementary HV MAD Cohort in Part 1, a set of adult subjects diagnosed with CF currently on a stable ivacaftor/lumacaftor background therapy for a minimum of three months will participate in the Part 2 complementary CF MAD cohort. Subjects will be randomized to receive either PTI-801 or placebo QD for a total of 14 days.
Following the conclusion of CF MAD Cohort 1 in Part 2, a set of adult subjects diagnosed with CF not currently receiving or have received background CFTR modulator therapy for a minimum of 30 days prior to Day 1 will participate in the Part 2 CF PTI-801 and PTI-808 co-administration cohort. Subjects will be randomized to receive either PTI-801 co-administered with PTI-808 or placebos QD for a total of 14 days.
Following the conclusion of the CF MAD Cohort 1 in Part 2, a set of adult subjects diagnosed with CF currently on a stable tezacaftor/ivacaftor background therapy for a minimum of one month will participate in the Part 2 complementary CF cohort. Subjects will be randomized to receive either PTI-801 or placebo QD for a total of 14 days.
Conditions
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Study Design
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RANDOMIZED
SEQUENTIAL
TREATMENT
TRIPLE
Study Groups
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SAD HV PTI-801 Active - Complete
The safety, tolerability, and pharmacokinetic profile of PTI-801 will be evaluated following a single dose of PTI-801. Three cohorts are planned for evaluation where subjects will be randomized to PTI-801 or placebo.The subjects will be followed for 7 days post dose.
PTI-801
Active
SAD HV PTI-801 Placebo - Complete
The safety, tolerability, and pharmacokinetic profile of PTI-801 will be evaluated following a single dose of PTI-801. Three cohorts are planned for evaluation where subjects will be randomized to PTI-801 or placebo.The subjects will be followed for 7 days post dose.
Placebo
Placebo
MAD HV PTI-801 Active - Complete
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 cohorts. Subjects will be randomized to either PTI-801 or placebo. Each dose will be administered once daily (QD) for a total of 7 days. Follow up visits will occur on Days 10, 12 and 14.
PTI-801
Active
MAD HV PTI-801 Placebo - Complete
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 cohorts. Subjects will be randomized to either PTI-801 or placebo. Each dose will be administered once daily (QD) for a total of 7 days. Follow up visits will occur on Days 10, 12 and 14.
Placebo
Placebo
FE HV PTI-801 Active - Complete
Following the conclusion of SAD groups and after sufficient review of study data and approval by the SRC, a third set of healthy adult subjects will participate in the Food Effect cohort. Subjects will be randomized to Fed or Fasted on Days 1 and 12. Follow up visits will occur 7 days post Day 12 dose.
PTI-801
Active
DDI HV PTI-801 Active - Complete
Following the conclusion of HV MAD Cohort 2 and after sufficient review of study data and approval by the SRC, a fourth set of healthy adult subjects will participate in the Drug-Drug Interactions cohort. Subjects will receive a 3-drug cocktail consisting of caffeine, bupropion, and midazolam on Day 1. On Day 4, subjects will be randomized to receive either PTI-801 or placebo QD for a total of 12 days. On Day 17, subjects will receive the 3-drug cocktail in combination with PTI-801 or placebo. Subjects will remain in clinic until Day 20. A follow up visit will occur on Day 24.
PTI-801
Active
DDI HV PTI-801 Placebo - Complete
Following the conclusion of HV MAD Cohort 2 and after sufficient review of study data and approval by the SRC, a fourth set of healthy adult subjects will participate in the Drug-Drug Interactions cohort. Subjects will receive a 3-drug cocktail consisting of caffeine, bupropion, and midazolam on Day 1. On Day 4, subjects will be randomized to receive either PTI-801 or placebo QD for a total of 12 days. On Day 17, subjects will receive the 3-drug cocktail in combination with PTI-801 or placebo. Subjects will remain in clinic until Day 20. A follow up visit will occur on Day 24.
Placebo
Placebo
MAD Cohort 1-3 CF PTI-801 Active - Complete
Adult subjects diagnosed with CF currently on stable ivacaftor/lumacaftor background therapy for a minimum of three months will participate in the Part 2 complementary CF MAD cohort. The CF MAD treatment group is comprised of 3 cohorts. Subjects will be randomized to receive either PTI-801 or placebo QD for a total of 14 days. A follow up visit will occur on Day 21.
PTI-801
Active
MAD Cohort 1-3 CF PTI-801 Placebo - Complete
Adult subjects diagnosed with CF currently on stable ivacaftor/lumacaftor background therapy for a minimum of three months will participate in the Part 2 complementary CF MAD cohort. The CF MAD treatment group is comprised of 3 cohorts. Subjects will be randomized to receive either PTI-801 or placebo QD for a total of 14 days. A follow up visit will occur on Day 21.
Placebo
Placebo
Cohort 4 CF PTI-801 Active co-admin PTI-808 Active - Complete
Adult subjects diagnosed with CF not currently receiving a CFTR modulator therapy within 30 days prior to Day 1 will participate in the Part 2 CF Cohort 4. Subjects will be randomized to receive either PTI-801 co-administered with PTI-808 or placebos QD.
PTI-801
Active
PTI-808
Active
Cohort 4 CF PTI-801 Placebo co-admin PTI-808 Placebo- Complete
Adult subjects diagnosed with CF not currently receiving a CFTR modulator therapy within 30 days prior to Day 1 will participate in the Part 2 CF Cohort 4. Subjects will be randomized to receive either PTI-801 co-administered with PTI-808 or placebos QD.
Placebo
Placebo
Placebo
Placebo
Cohort 5 CF PTI-801 Active co-admin with PTI-808 Active
Adult subjects diagnosed with CF not currently receiving a CFTR modulator therapy within 30 days prior to Day 1 will participate in the Part 2 CF Cohort 5. Subjects will be randomized to receive either PTI-801 co-administered with PTI-808 or placebos QD.
PTI-801
Active
PTI-808
Active
Cohort 5 CF PTI-801 Placebo co-admin with PTI-808 Placebo
Adult subjects diagnosed with CF not currently receiving a CFTR modulator therapy within 30 days prior to Day 1 will participate in the Part 2 CF Cohort 5. Subjects will be randomized to receive either PTI-801 co-administered with PTI-808 or placebos QD.
Placebo
Placebo
Placebo
Placebo
Cohort 6 CF PTI-801 Active
Adult subjects diagnosed with CF currently on stable tezacaftor/ivacaftor background therapy for a minimum of one month will participate in the Part 2 complementary CF MAD cohort. Subjects will be randomized to receive either PTI-801 or placebo QD.
PTI-801
Active
Cohort 6 CF PTI-801 Placebo
Adult subjects diagnosed with CF currently on stable tezacaftor/ivacaftor background therapy for a minimum of one month will participate in the Part 2 complementary CF MAD cohort. Subjects will be randomized to receive either PTI-801 or placebo QD.
Placebo
Placebo
Interventions
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PTI-801
Active
Placebo
Placebo
PTI-808
Active
Placebo
Placebo
Eligibility Criteria
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Inclusion Criteria
* Body mass index (BMI) ≥18 to \<30 kg/m2.
* Subject must be a nonsmoker and a nontobacco user for a minimum of 30 days prior to screening and for the duration of the study.
* Confirmed diagnosis of CF with the F508del/F508del genotype 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
Part 2 Cohorts 1-3 Additional Inclusion Criterion:
* Stable on ivacaftor/lumacaftor dosing for both label indication and per label dosing for a minimum of 3 months at the time of dosing
Part 2 Cohort 6 Additional Inclusion Criterion:
* Stable on tezacaftor/ivacaftor dosing for both label indication and per label dosing for a minimum of 1 month at the time dosing
Exclusion Criteria
* Presence of prolonged QT/ Corrected QT Interval (QTc) interval with Fridericia's correction formula (QTcF) \>450 msec at screening.
* Abnormal liver function as defined by aspartate aminotransferase (AST), alanine aminotransferase (ALT) or bilirubin \> upper limit of the normal range.
* Abnormal renal function at screening defined as: Creatinine clearance \<80 mL/min using the Cockcroft-Gault equation.
* Participation in another clinical trial or treatment with an investigational agent within 30 days or 5 half-lives, whichever is longer, prior to Study Day 1.
* History of cancer within the past 5 years (excluding nonmelanoma skin cancer).
* History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator.
* 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.
* Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCVAb).
* Has donated blood within 3 months of screening or plans to donate blood within 3 months of study completion.
* Concomitant use of known strong or moderate inhibitors or inducers of CYP1A2, CYP2B6, and CYP3A4 within 14 days or 5 half-lives (whichever is longer) prior to Day 1 and through the last PK sampling point on Day 20
* Use of grapefruit- or Seville orange-containing products within 48 hours prior to Day 1 and through the last PK sampling point on Day 20
* Use of alcohol- or caffeine-containing products within 48 hours prior to Day 1 and through the last PK sampling point on Day 20
* 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 (excluding cervical cancer in situ with curative therapy for at least one year prior to screening and non-melanoma skin cancer)
* 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
Part 2 Cohort's 4 and 5 Additional Exclusion Criterion:
* Currently taking or has taken a CFTR modulator within 30 days prior to initial dose of study drugs
18 Years
ALL
Yes
Sponsors
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Proteostasis Therapeutics, Inc.
INDUSTRY
Responsible Party
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Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Providence Alaska Medical Center
Anchorage, Alaska, United States
Stanford University Medical Center
Stanford, California, United States
National Jewish Health
Denver, Colorado, United States
Central Florida Pulmonary Group
Altamonte Springs, Florida, United States
University of Florida College of Medicine
Gainesville, Florida, United States
University of Miami Health System
Miami, Florida, United States
St. Luke's CF Center of Idaho
Boise, Idaho, United States
Northwestern University Memorial Hospital
Chicago, Illinois, United States
OSF Saint Francis Medical Center
Peoria, Illinois, United States
University of Iowa
Iowa City, Iowa, United States
Maine Medical Center
Portland, Maine, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Boston Children's Hospital
Boston, Massachusetts, United States
University of Michigan Health System
Ann Arbor, Michigan, United States
Children's Mercy Kansas City
Kansas City, Missouri, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Children's Lung Specialists
Las Vegas, Nevada, United States
Columbia University Medical Center
New York, New York, United States
Mount Sinai Beth Israel
New York, New York, United States
New York Medical College
Valhalla, New York, United States
Duke University Health System
Durham, North Carolina, United States
Akron Children's Hospital
Akron, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Toledo Children's Hospital
Toledo, Ohio, United States
Santiago Reyes, M.D. P.C.
Oklahoma City, Oklahoma, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
ICON Early Phase Services
San Antonio, Texas, United States
University of Texas Health Science Center at Tyler
Tyler, Texas, United States
University of Utah
Salt Lake City, Utah, United States
Virginia Commonwealth University
Richmond, Virginia, United States
St. Paul's Hospital
Vancouver, British Columbia, Canada
Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Québec, , Canada
University of Copenhagen Rigshospitalet
Copenhagen, , Denmark
Charite - Campus Virchow-Klinikum
Berlin, , Germany
Stockholm CF Center
Stockholm, , Sweden
Countries
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Other Identifiers
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PTI-801-01
Identifier Type: -
Identifier Source: org_study_id
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