Healthy VolunteerPhase 1NCT03140527
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
A Phase 1 study testing PTI-801 and PTI-808 in people with Healthy Volunteer and Cystic Fibrosis, run by Proteostasis Therapeutics, Inc. at 38 sites in 5 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteer, Cystic Fibrosis
- What is being tested?
- PTI-801 and PTI-808
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 171 participants
- Where
- 38 sitesin 5 countries
- Study dates
- 10 Apr 2017to 27 Feb 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Trial locations and contacts
38 sites in 5 countries.
38 sites in 5 countries
United States33 sites
Akron Children's Hospital
Akron, Ohio, 44308
Central Florida Pulmonary Group
Altamonte Springs, Florida, 32803
Providence Alaska Medical Center
Anchorage, Alaska, 99508
University of Michigan Health System
Ann Arbor, Michigan, 48109
University of Alabama at Birmingham
Birmingham, Alabama, 35233
St. Luke's CF Center of Idaho
Boise, Idaho, 83712
Massachusetts General Hospital
Boston, Massachusetts, 02114
Boston Children's Hospital
Boston, Massachusetts, 02115
Medical University of South Carolina
Charleston, South Carolina, 29425
Northwestern University Memorial Hospital
Chicago, Illinois, 60611
Nationwide Children's Hospital
Columbus, Ohio, 43205
National Jewish Health
Denver, Colorado, 80206
Duke University Health System
Durham, North Carolina, 27710
University of Florida College of Medicine
Gainesville, Florida, 32610
University of Iowa
Iowa City, Iowa, 52242
Children's Mercy Kansas City
Kansas City, Missouri, 64108
Children's Lung Specialists
Las Vegas, Nevada, 89107
University of Miami Health System
Miami, Florida, 33136
Columbia University Medical Center
New York, New York, 10001
Mount Sinai Beth Israel
New York, New York, 10003
Santiago Reyes, M.D. P.C.
Oklahoma City, Oklahoma, 73112
University of Nebraska Medical Center
Omaha, Nebraska, 68198
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15244
Maine Medical Center
Portland, Maine, 04102
Virginia Commonwealth University
Richmond, Virginia, 23298
University of Utah
Salt Lake City, Utah, 84132
ICON Early Phase Services
San Antonio, Texas, 78209
Stanford University Medical Center
Stanford, California, 94305
Toledo Children's Hospital
Toledo, Ohio, 43606
University of Texas Health Science Center at Tyler
Tyler, Texas, 75708
New York Medical College
Valhalla, New York, 10595
Canada2 sites
Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Québec, G1V 4G5
St. Paul's Hospital
Vancouver, British Columbia, V6Z1Y6
About this study
Official title: 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.
Read the 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.
- Conditions
- Healthy Volunteer, Cystic Fibrosis
- Being tested
- PTI-801, Placebo, PTI-808
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PTI-801Drug
Active
PlaceboDrug
Placebo
PTI-808Drug
Active
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| SAD HV PTI-801 Active - Complete | Active comparator | 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. Receives: Drug: PTI-801 |
| SAD HV PTI-801 Placebo - Complete | Placebo comparator | 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. Receives: Drug: Placebo |
| MAD HV PTI-801 Active - Complete | Active comparator | 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. Receives: Drug: PTI-801 |
| MAD HV PTI-801 Placebo - Complete | Placebo comparator | 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. Receives: Drug: Placebo |
| FE HV PTI-801 Active - Complete | Active comparator | 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. Receives: Drug: PTI-801 |
| DDI HV PTI-801 Active - Complete | Active comparator | 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. Receives: Drug: PTI-801 |
| DDI HV PTI-801 Placebo - Complete | Placebo comparator | 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. Receives: Drug: Placebo |
| MAD Cohort 1-3 CF PTI-801 Active - Complete | Active comparator | 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. Receives: Drug: PTI-801 |
| MAD Cohort 1-3 CF PTI-801 Placebo - Complete | Placebo comparator | 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. Receives: Drug: Placebo |
| Cohort 4 CF PTI-801 Active co-admin PTI-808 Active - Complete | Active comparator | 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. Receives: Drug: PTI-801; Drug: PTI-808 |
| Cohort 4 CF PTI-801 Placebo co-admin PTI-808 Placebo- Complete | Placebo comparator | 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. Receives: Drug: Placebo |
| Cohort 5 CF PTI-801 Active co-admin with PTI-808 Active | Active comparator | 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. Receives: Drug: PTI-801; Drug: PTI-808 |
| Cohort 5 CF PTI-801 Placebo co-admin with PTI-808 Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
| Cohort 6 CF PTI-801 Active | Active comparator | 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. Receives: Drug: PTI-801 |
| Cohort 6 CF PTI-801 Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: baseline to up to 14 days
Part 1 SAD: Apparent terminal half-life (t1/2) of single oral dose
Measured: through 72-hours post dose
Part 1 SAD: Time to reach maximum plasma concentration (Tmax) of single oral dose
Measured: through 72-hours post dose
Part 1 SAD: Maximum plasma concentration (Cmax) of single oral dose
Measured: 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
Measured: 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
Measured: through 72-hours post dose
Part 1 SAD: AUC from time 0 to infinity (AUC0-inf)
using noncompartmental methods as appropriate of single dose
Measured: through 72-hours post dose
Part 1 MAD HV: Apparent terminal half-life (t1/2) of multiple oral doses
Measured: through 72-hours post last dose
Part 1 MAD HV: Time to reach maximum plasma concentration (Tmax) of multiple oral doses
Measured: through 72-hours post last dose
Part 1 MAD HV: Maximum plasma concentration (Cmax) of multiple oral doses
Measured: 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
Measured: 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
Measured: through 72-hour post last dose
Part 1 MAD HV: AUC from time 0 to infinity (AUC0-inf) of multiple oral doses
using noncompartmental methods as appropriate of multiple oral doses
Measured: 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
Measured: 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
Measured: through 24-hour post last dose
Part 1 FE: Time to reach maximum plasma concentration (Tmax)
Measured: through 72-hour post last dose
Part 1 FE :Maximum plasma concentration (Cmax)
Measured: 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)
Measured: through 72-hour post last dose
Part 1 FE: AUC from time 0 to infinity (AUC0-inf)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: baseline through Day 21
Secondary outcomes (16)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: through 72-hours post dose
Part 2 CF: Time to reach maximum plasma concentration (Tmax)
Measured: Day 1 through Day 15
Part 2 CF: Maximum plasma concentration (Cmax)
Measured: Day 1 through Day 15
Part 2 CF: Area under the concentration-time curve from time 0 to time of last measurable concentration (AUClast)
Measured: 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
Measured: Day 1 through Day 15
Part 2 CF: change in forced expiratory volume in one second (FEV1) over time
Measured: baseline through Day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2017
- Study start10 Apr 2017
- Primary completion27 Feb 2020
- Study completion27 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 171 participants (actual)
Sponsor and investigators
- Lead sponsor
- Proteostasis Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03140527
- Sponsor's protocol ID
- PTI-801-01
- Status last verified
- Apr 2020
- First submitted
- 27 Apr 2017
- Last updated
- 30 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03140527
- Acronym / sponsor ID
- PTI-801-01
- Conditions
- Healthy Volunteer, Cystic Fibrosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 171 participants (actual)
- Lead sponsor
- Proteostasis Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Apr 2017 (actual)
- Primary completion
- 27 Feb 2020 (actual)
- Study completion
- 27 Feb 2020 (actual)
- First posted
- 4 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| SAD HV PTI-801 Active - Complete | Active comparator | Drug: PTI-801The 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. |
| SAD HV PTI-801 Placebo - Complete | Placebo comparator | Drug: PlaceboThe 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. |
| MAD HV PTI-801 Active - Complete | Active comparator | Drug: PTI-801Following 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. |
| MAD HV PTI-801 Placebo - Complete | Placebo comparator | Drug: PlaceboFollowing 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. |
| FE HV PTI-801 Active - Complete | Active comparator | Drug: PTI-801Following 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. |
| DDI HV PTI-801 Active - Complete | Active comparator | Drug: PTI-801Following 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. |
| DDI HV PTI-801 Placebo - Complete | Placebo comparator | Drug: PlaceboFollowing 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. |
| MAD Cohort 1-3 CF PTI-801 Active - Complete | Active comparator | Drug: PTI-801Adult 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. |
| MAD Cohort 1-3 CF PTI-801 Placebo - Complete | Placebo comparator | Drug: PlaceboAdult 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. |
| Cohort 4 CF PTI-801 Active co-admin PTI-808 Active - Complete | Active comparator | Drug: PTI-801, Drug: PTI-808Adult 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. |
| Cohort 4 CF PTI-801 Placebo co-admin PTI-808 Placebo- Complete | Placebo comparator | Drug: PlaceboAdult 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. |
| Cohort 5 CF PTI-801 Active co-admin with PTI-808 Active | Active comparator | Drug: PTI-801, Drug: PTI-808Adult 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. |
| Cohort 5 CF PTI-801 Placebo co-admin with PTI-808 Placebo | Placebo comparator | Drug: PlaceboAdult 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. |
| Cohort 6 CF PTI-801 Active | Active comparator | Drug: PTI-801Adult 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. |
| Cohort 6 CF PTI-801 Placebo | Placebo comparator | Drug: PlaceboAdult 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PTI-801Active | Drug | Cohort 4 CF PTI-801 Active co-admin PTI-808 Active - Complete, Cohort 5 CF PTI-801 Active co-admin with PTI-808 Active, Cohort 6 CF PTI-801 Active, DDI HV PTI-801 Active - Complete, FE HV PTI-801 Active - Complete, MAD Cohort 1-3 CF PTI-801 Active - Complete, MAD HV PTI-801 Active - Complete, SAD HV PTI-801 Active - Complete |
| PlaceboPlacebo | Drug | Cohort 4 CF PTI-801 Placebo co-admin PTI-808 Placebo- Complete, Cohort 5 CF PTI-801 Placebo co-admin with PTI-808 Placebo, Cohort 6 CF PTI-801 Placebo, DDI HV PTI-801 Placebo - Complete, MAD Cohort 1-3 CF PTI-801 Placebo - Complete, MAD HV PTI-801 Placebo - Complete, SAD HV PTI-801 Placebo - Complete |
| PTI-808Active | Drug | Cohort 4 CF PTI-801 Active co-admin PTI-808 Active - Complete, Cohort 5 CF PTI-801 Active co-admin with PTI-808 Active |
| PlaceboPlacebo | Drug | Cohort 4 CF PTI-801 Placebo co-admin PTI-808 Placebo- Complete, Cohort 5 CF PTI-801 Placebo co-admin with PTI-808 Placebo |
Primary outcome
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
Part 1 SAD: Apparent terminal half-life (t1/2) of single oral dose
Time frame: 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
Part 1 SAD: Maximum plasma concentration (Cmax) of single oral dose
Time frame: 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
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
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
Part 1 MAD HV: Apparent terminal half-life (t1/2) of multiple oral doses
Time frame: 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
Part 1 MAD HV: Maximum plasma concentration (Cmax) of multiple oral doses
Time frame: 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
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
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
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
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
Part 1 FE: Time to reach maximum plasma concentration (Tmax)
Time frame: through 72-hour post last dose
Part 1 FE :Maximum plasma concentration (Cmax)
Time frame: 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
Part 1 FE: AUC from time 0 to infinity (AUC0-inf)
Time frame: 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
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
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
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
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
16 secondary outcomes
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
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
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
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
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
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
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
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
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
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
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
Part 2 CF: Time to reach maximum plasma concentration (Tmax)
Time frame: Day 1 through Day 15
Part 2 CF: Maximum plasma concentration (Cmax)
Time frame: 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
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
Part 2 CF: change in forced expiratory volume in one second (FEV1) over time
Time frame: baseline through Day 21
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
38 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PTI-801 and PTI-808 in people with Healthy Volunteer and Cystic Fibrosis, run by Proteostasis Therapeutics, Inc. at 38 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Canada, Denmark, Germany, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 24 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2020.