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

April 28, 2020 updated by: Proteostasis Therapeutics, Inc.

A Multi-Center, Randomized, Placebo-Controlled, Phase 1, Two-Part Study Designed to Assess 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

This trial will consist of two parts: Part 1 and Part 2. Part 1 will enroll adult healthy volunteers (HV) into four treatment groups. The first group will enroll HV into a single ascending dose (SAD) treatment group consisting of three cohorts. The second group will enroll HV into a multiple ascending dose (MAD) treatment group consisting of three cohorts. The third group will enroll HV into a food effect (FE) treatment group consisting of one cohort. The fourth group will enroll HV into a drug-drug interactions (DDI) treatment group consisting of one cohort. Approximately 76 subjects will be enrolled in Part 1.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PART 1 The SAD treatment group is comprised of three cohorts where HV will be randomized to either PTI-801 or placebo. The MAD treatment group is comprised of three cohorts where subjects will be randomized to receive either PTI-801 or placebo once daily (QD) for a total of 7 days. HV will participate in a FE treatment group ,the FE treatment group is comprised of one cohort where subjects will be randomized to receive an initial single dose of PTI-801 either after an overnight fast of at least 10 hours (fasted group) or after an overnight fast of at least 10 hours followed by the consumption of a high fat high and high calorie meal (fed group). A set of HV will participate in a DDI treatment group. The DDI treatment group is comprised of one cohort where 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.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
171

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Quebec, Canada, G1V 4G5
        • Institut Universitaire De Cardiologie Et De Pneumologie De Québec
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z1Y6
        • St. Paul's Hospital
  • Denmark
      • Copenhagen, Denmark, 2100
        • University of Copenhagen Rigshospitalet
  • Germany
      • Berlin, Germany, 10117
        • Charité - Campus Virchow-Klinikum
  • Sweden
      • Stockholm, Sweden, 141 86
        • Stockholm CF center
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Providence Alaska 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
      • Gainesville, Florida, United States, 32610
        • University of Florida College of Medicine
      • Miami, Florida, United States, 33136
        • University of Miami Health System
    • Idaho
      • Boise, Idaho, United States, 83712
        • St. Luke's CF Center of Idaho
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University Memorial Hospital
      • Peoria, Illinois, United States, 61637
        • OSF Saint Francis Medical Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Maine
      • Portland, Maine, United States, 04102
        • Maine Medical Center
    • 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
        • University of Michigan Health System
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Kansas City
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • Nevada
      • Las Vegas, Nevada, United States, 89107
        • Children's Lung Specialists
    • New York
      • New York, New York, United States, 10003
        • Mount Sinai Beth Israel
      • New York, New York, United States, 10001
        • Columbia University Medical Center
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Health System
    • Ohio
      • Akron, Ohio, United States, 44308
        • Akron Children's Hospital
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
      • Toledo, Ohio, United States, 43606
        • Toledo Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Santiago Reyes, M.D. P.C.
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15244
        • Children's Hospital of Pittsburgh of UPMC
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Texas
      • San Antonio, Texas, United States, 78209
        • ICON Early Phase Services
      • Tyler, Texas, United States, 75708
        • University of Texas Health Science Center at Tyler
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Part 1 Inclusion Criteria:

  • Adults age 18 to 55 years old, inclusive, at the time of informed consent.
  • 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.

Part 1 Exclusion Criteria:

  • 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.
  • 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.

Part 1 HV DDI Cohort Additional Exclusion Criteria:

  • 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

Part 2 Inclusion Criteria:

  • 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

Part 2 Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: 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.
Drug: PTI-801
Active
Placebo Comparator: 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.
Drug: Placebo
Placebo
Active Comparator: 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.
Drug: PTI-801
Active
Placebo Comparator: 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.
Drug: Placebo
Placebo
Active Comparator: 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.
Drug: PTI-801
Active
Active Comparator: 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.
Drug: PTI-801
Active
Placebo Comparator: 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.
Drug: Placebo
Placebo
Active Comparator: 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.
Drug: PTI-801
Active
Placebo Comparator: 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.
Drug: Placebo
Placebo
Active Comparator: 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.
Drug: PTI-801
Active
Drug: PTI-808
Active
Placebo Comparator: 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.
Drug: Placebo
Placebo
Active Comparator: 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.
Drug: PTI-801
Active
Drug: PTI-808
Active
Placebo Comparator: 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.
Drug: Placebo
Placebo
Active Comparator: 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.
Drug: PTI-801
Active
Placebo Comparator: 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.
Drug: Placebo
Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part 1 SAD and MAD HV: Safety and tolerability measured by number of subjects who experience adverse events and potential clinically significant changes in safety labs, electrocardiograms (ECGs), physical examinations, and vital signs
Time Frame: baseline to up to 14 days
baseline to up to 14 days
Part 1 SAD: Apparent terminal half-life (t1/2) of single oral dose
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 SAD: Time to reach maximum plasma concentration (Tmax) of single oral dose
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 SAD: Maximum plasma concentration (Cmax) of single oral dose
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 SAD: Area under the concentration-time curve from time 0 to 24 hours post administration (AUC0-24) of a single oral dose
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 SAD: Area under the concentration-time curve from time 0 to time of last measurable concentration (AUC0-last) of a single oral dose
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 SAD: AUC from time 0 to infinity (AUC0-inf)
Time Frame: through 72-hours post dose
using noncompartmental methods as appropriate of single dose
through 72-hours post dose
Part 1 MAD HV: Apparent terminal half-life (t1/2) of multiple oral doses
Time Frame: through 72-hours post last dose
through 72-hours post last dose
Part 1 MAD HV: Time to reach maximum plasma concentration (Tmax) of multiple oral doses
Time Frame: through 72-hours post last dose
through 72-hours post last dose
Part 1 MAD HV: Maximum plasma concentration (Cmax) of multiple oral doses
Time Frame: through 72-hours post last dose
through 72-hours post last dose
Part 1 MAD HV: Area under the concentration-time curve from time 0 to 24 hours post administration (AUC0-24) of multiple oral doses
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 MAD HV: Area under the concentration-time curve from time 0 to time of last measurable concentration (AUClast) of multiple oral doses
Time Frame: through 72-hour post last dose
through 72-hour post last dose
Part 1 MAD HV: AUC from time 0 to infinity (AUC0-inf) of multiple oral doses
Time Frame: through 72-hour post last dose
using noncompartmental methods as appropriate of multiple oral doses
through 72-hour post last dose
Part 1 MAD HV: Cumulative amount of PTI-801 excreted unchanged in urine (Ae) as appropriate of multiple oral doses
Time Frame: through 24-hour post last dose
through 24-hour post last dose
Part 1 MAD HV: Cumulative amount of PTI-801 unchanged in renal clearance (CLR) as appropriate of multiple oral doses
Time Frame: through 24-hour post last dose
through 24-hour post last dose
Part 1 FE: Time to reach maximum plasma concentration (Tmax)
Time Frame: through 72-hour post last dose
through 72-hour post last dose
Part 1 FE :Maximum plasma concentration (Cmax)
Time Frame: through 72-hour post last dose
through 72-hour post last dose
Part 1 FE: Area under the concentration-time curve from time 0 to time of last measurable concentration (AUCt)
Time Frame: through 72-hour post last dose
through 72-hour post last dose
Part 1 FE: AUC from time 0 to infinity (AUC0-inf)
Time Frame: through 72-hour post last dose
through 72-hour post last dose
Part 1 DDI: Safety and tolerability measured by number of subjects who experience adverse events and potential clinically significant changes in safety labs, electrocardiograms (ECGs), physical examinations, and vital signs
Time Frame: baseline through 7 days post last dose
baseline through 7 days post last dose
Part 1 DDI: Maximum plasma concentration (Cmax) of caffeine, bupropion, and midazolam with and without multiple oral doses of PTI-801
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 DDI: Area under the concentration-time curve from time 0 to time of last measurable concentration (AUClast) of caffeine, bupropion, and midazolam with and without multiple oral doses of PTI-801
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 DDI: Area under the concentration-time curve from time 0 to infinity (AUCinf) of caffeine, bupropion, and midazolam with and without multiple oral doses of PTI-801
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 2 CF: Safety and tolerability measured by number of subjects who experience adverse events and potential clinically significant changes in safety labs, electrocardiograms (ECGs), physical examinations, and vital signs
Time Frame: baseline through Day 21
baseline through Day 21

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Part 1 FE: Safety and tolerability measured by number of subjects who experience adverse events and potential clinically significant changes in safety labs, electrocardiograms (ECGs), physical examinations, and vital signs
Time Frame: baseline through 7 days post last dose
baseline through 7 days post last dose
Part 1 DDI: Apparent terminal half-life (t1/2) of multiple oral doses of PTI-801 with and without caffeine, bupropion, and midazolam
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 DDI: Time to reach maximum plasma concentration (Tmax) of the metabolites of caffeine, bupropion, and midazolam after single oral doses of caffeine, bupropion, midazolam, and with and without multiple oral doses of PTI-801
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 DDI: Maximum plasma concentration (Cmax) of the metabolites of caffeine, bupropion, and midazolam after single oral doses of caffeine, bupropion, midazolam, and with and without multiple oral doses of PTI-801
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 DDI: AUClast of the metabolites of caffeine, bupropion, and midazolam after single oral doses of caffeine, bupropion, midazolam, and with and without multiple oral doses of PTI-801
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 DDI: Area under the concentration-time curve from time 0 to 24 hours post administration (AUC0-24) of multiple oral doses of PTI-801 with and without caffeine, bupropion, and midazolam
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 DDI: Metabolite over parent ratio of Cmax of single oral doses of the metabolites of caffeine, bupropion, and midazolam after single oral doses of caffeine, bupropion, midazolam, and with and without multiple oral doses of PTI-801
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 DDI: Metabolite over parent ratio of AUClast of the metabolites of caffeine, bupropion, and midazolam after single oral doses of caffeine, bupropion, midazolam, and with and without multiple oral doses of PTI-801
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 DDI: Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI-801 with and without caffeine, bupropion, and midazolam
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 DDI: Maximum plasma concentration (Cmax) of multiple oral doses of PTI-801 with and without caffeine, bupropion, and midazolam
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 1 DDI: Area under the concentration-time curve from time 0 to time of last measurable concentration (AUClast) of multiple oral doses of PTI-801 with and without caffeine, bupropion, and midazolam
Time Frame: through 72-hours post dose
through 72-hours post dose
Part 2 CF: Time to reach maximum plasma concentration (Tmax)
Time Frame: Day 1 through Day 15
Day 1 through Day 15
Part 2 CF: Maximum plasma concentration (Cmax)
Time Frame: Day 1 through Day 15
Day 1 through Day 15
Part 2 CF: Area under the concentration-time curve from time 0 to time of last measurable concentration (AUClast)
Time Frame: Day 1 through Day 15
Day 1 through Day 15
Part 2 CF: Area under the concentration-time curve from time 0 to time of last measurable concentration (AUClast) of multiple oral doses of PTI-808 with PTI-801
Time Frame: Day 1 through Day 15
Day 1 through Day 15
Part 2 CF: change in forced expiratory volume in one second (FEV1) over time
Time Frame: baseline through Day 21
baseline through Day 21

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
Part 1 SAD, MAD HV, and FE: The effect of PTI-801 on the QT interval as measured by holter monitoring
Time Frame: baseline through 7 days post last dose
baseline through 7 days post last dose
Part 1: change in nasal epithelial mRNA and protein expression over time
Time Frame: baseline through 7 days post last dose
baseline through 7 days post last dose
Part 2 CF: change in sweat chloride over time
Time Frame: baseline through Day 21
baseline through Day 21
Part 2 CF: change in nasal epithelial mRNA and protein expression over time
Time Frame: baseline through Day 21
baseline through Day 21
Part 2 CF: change in weight and BMI over time
Time Frame: baseline through Day 21
baseline through Day 21
Part 2 CF: change in blood glucose over time
Time Frame: baseline through Day 21
baseline through Day 21

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Proteostasis Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 10, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 27, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 27, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 27, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 2, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 4, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 30, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 28, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PTI-801-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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