Healthy Volunteer - CompletePhase 1/2NCT03251092
Study Designed to Assess the Safety, Tolerability and PK of PTI-808 in Healthy Volunteers and in Adults With Cystic Fibrosis
A Phase 1/2 study testing PTI-808, PTI-428 and PTI-801 in people with Healthy Volunteer - Complete and Cystic Fibrosis - Complete, run by Proteostasis Therapeutics, Inc. at 48 sites in 9 countries.
Trial summary
Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD), multiple ascending dose (MAD), and Food Effect (FE) treatment groups. The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy adult subjects will be randomized to receive a single dose of… Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteer - Complete, Cystic Fibrosis - Complete
- What is being tested?
- PTI-808, PTI-428 and PTI-801
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 179 participants
- Where
- 48 sitesin 9 countries
- Study dates
- 17 Jul 2017to 23 Dec 2019
- Phase
- Phase 1/2
- 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 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Part 1 and Part 2 Inclusion Criteria:
- Adults aged 18 to 55 years old, inclusive, at the time of informed consent
- Body mass index ≥18 and <30 kg/m2
- Subject must be a non-smoker and non-tobacco user for a minimum of 30 days prior to screening and for the duration of the study.
- Subject understands the full nature and purpose of the study, including possible risks and side effects, and is willing and able to comply with all compulsory study procedures and provides informed consent/permission prior to any study procedures being performed.
- Females of childbearing potential and males capable of fathering a child must meet the contraception requirements
Part 1 \& Part 2 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
- Prolonged QT interval with Fridericia's correction >450 msec at screening
- Abnormal liver function as defined by aspartate transaminase (AST), alanine transaminase (ALT), or bilirubin >1.5× the upper limit of the normal range
- Abnormal renal function at screening defined as creatinine clearance <90 mL/min using the Cockroft-Gault equation
- Clinically significant screening results that would exclude subject from the study (e.g., medical histories, PE, ECGs, vital signs, and laboratory profiles) as deemed by the investigator
- Participation in another clinical study or treatment with an investigational agent within 30 days or five half-lives, whichever is longer, prior to Study Day 1
- History of cancer within the past 5 years (excluding non-melanoma 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)
- Clinically significant infection within 3 months of screening as determined by the investigator
- Known or suspected hypersensitivity or idiosyncratic reaction to study medication or any components thereof
- Has donated blood within 3 months of screening or plans to donate blood within 3 months of study completion
- Pregnant or nursing women
- Any conditions that, in the opinion of the investigator, would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study
- Use of prohibited medications within 14 days prior to dosing of study drug
Part 3 CF Inclusion Criteria:
- Confirmed diagnosis of CF with the F508del/F508del genotype
- 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 3 CF 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
- Currently taking or has taken a CFTR modulator within 30 days prior to initial dose of study drugs
Part 4 CF Inclusion Criteria:
- Confirmed diagnosis of CF with either the F508del CFTR homozygous genotype on record or for heterozygote subjects, only one copy of the F508del CFTR mutation on record
- 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 4 CF 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 28 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 of 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
- Currently taking or has taken a CFTR modulator within 14 days prior to the screening visit
Trial locations and contacts
48 sites in 9 countries.
48 sites in 9 countries
United States22 sites
Central Florida Pulmonary Group
Altamonte Springs, Florida, 32803
Michigan Medicine, University of Michigan
Ann Arbor, Michigan, 48109
Emory Children's Center
Atlanta, Georgia, 30322
Johns Hopkins University
Baltimore, Maryland, 21287
Billings Clinic
Billings, Montana, 59101
Massachusetts General Hospital
Boston, Massachusetts, 02114
Boston Children's Hospital
Boston, Massachusetts, 02115
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27517
Medical University of South Carolina
Charleston, South Carolina, 29425
Northwestern Memorial Hospital
Chicago, Illinois, 60611
National Jewish Health
Denver, Colorado, 80206
Harper University Hospital
Detroit, Michigan, 48201
Children's Mercy
Kansas City, Missouri, 64108
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
University of Minnesota
Minneapolis, Minnesota, 55455
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of Utah
Salt Lake City, Utah, 84132
ICON Early Phase Services
San Antonio, Texas, 78209
Stanford University Medical Center
Stanford, California, 94305
Banner University of Arizona Medical Center
Tucson, Arizona, 85724
New York Medical College
Valhalla, New York, 10595
France6 sites
Hospices Civils de Lyon
Lyon, 69495
Hôpital Guillaume-et-René-Laennec
Nantes, Loire-Atlantique, 44093
Hôpital Pasteur
Nice, Alpes-Maritimes, 06001
Hôpital Cochin
Paris, 75014
Hôpital Haut Lévêque
Pessac, Gironde, 33600
Hôpital Maison Blanche Maladies respiratoires et allergologie
Reims, Marne, 51092
United Kingdom6 sites
Belfast City Hospital
Belfast, BT9 7AB
Birmingham Heartlands Hospital
Birmingham, West Midlands, B9 5SS
Western General Hospital
Edinburgh, Scotland, EH42XU
Royal Devon and Exeter Hospital
Exeter, Devon, EX2 5DW
King's College Hospital
London, SE59RS
University Hospital Southampton
Southampton, SO16 6YD
Germany5 sites
Charité Universitätsmedizin Berlin
Berlin, 10117
University Hospital Cologne
Cologne, 50937
Universitätsklinikum Essen
Essen, 45239
Klinikum der J.W. Goethe Universität
Frankfurt, 60590
Klinikum des Universität München
München, 81377
Canada4 sites
Centre hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, H2X3E4
McGill University Health Centre
Montreal, Quebec, H4A3J1
Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval
Québec, G1V4G5
St. Paul's Hospital
Vancouver, British Columbia, V6Z1Y6
Belgium2 sites
Universitair ziekenhuis Brussel
Brussels, 1090
UZ Leuven
Leuven, 3000
About this study
Official title: A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PTI-808 in Healthy Adult Subjects and in Adults With Cystic Fibrosis
Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD), multiple ascending dose (MAD), and Food Effect (FE) treatment groups.
The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and will be followed for 7 days post dose. A safety review committee (SRC) will convene after the completion of each cohort to evaluate safety and pharmacokinetic (PK) data.
Read more
Following the conclusion of the respective SAD level dose groups and after sufficient review of study data and approval by the SRC, a second set of healthy adult subjects will participate in an assigned MAD treatment group. The MAD treatment group is comprised of 3 ascending dose level cohorts where subjects will be randomized to receive either PTI-808 or placebo daily for 7 days and will be followed for 7 days after receiving the last dose.
Also following the conclusion of the respective SAD level dose groups, healthy adult subjects will participate in the FE treatment group.
Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive days.
Part 3 will enroll adult subjects with cystic fibrosis (CF) into a MAD treatment group consisting of 2 cohorts. Subjects will receive PTI-808 co-administered with PTI-801 and PTI-428. PTI-808 will be administered daily for 7 consecutive days followed by PTI-808 + PTI-801 + PTI-428 administered daily for 14 consecutive days.
Part 4 will enroll adult subjects with cystic fibrosis (CF) into 28-day cohorts. Subjects will receive PTI-808 co-administered with PTI-801 with or without PTI-428 versus matching placebo.
Read the detailed description
Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD), multiple ascending dose (MAD), and Food Effect (FE) treatment groups.
The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and will be followed for 7 days post dose.
The MAD treatment group is comprised of 3 ascending dose level cohorts where subjects will be randomized to receive either PTI-808 or placebo daily for 7 days and will be followed for 7 days after receiving the last dose.
Following the conclusion of the respective SAD level dose groups the food effect portion of the study will be initiated and subjects will be randomized to receive an initial single dose of PTI-808 either after an overnight fast of at least 10 hours (fasted group) or after an overnight fast of at least 10 hours followed the consumption of a high fat high calorie meal (fed group). After a 10 day washout period, subjects will cross over to the opposite group and receive a second dose of PTI-808. Subjects will be followed for up to 7 days following dosing.
Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive days.
Part 3 - Part 3 will enroll adult subjects with CF to assess the safety, tolerability, and PK of multiple ascending doses of PTI-808 co-administered with PTI-801 and PTI-428. Subjects will receive 7 days of PTI-808 or placebo followed by 14 days of PTI-808 or placebo co-administered with PTI-801+PTI-428 or matching placebos.
Part 4 - Part 4 will assess the safety, tolerability, PK, and the effects of PTI-808 co-administered with PTI-801 with or without PTI-428 over a 28-day treatment period in CF subjects who are either homozygous for the F508del CFTR genotype or are heterozygous for the F508del CFTR genotype. Subjects will be randomized to receive treatment with PTI-808 co-administered with PTI-801 with or without PTI-428 versus matching placebo.
- Being tested
- PTI-808, Placebo, PTI-428, PTI-801
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PTI-808Drug
Active
PlaceboDrug
Placebo
PTI-428Drug
Active
PTI-801Drug
Active
| Study group | Role | What they receive |
|---|---|---|
| SAD PTI-808 Active | Active comparator | Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo. Receives: Drug: PTI-808 |
| SAD PTI-808 Placebo | Placebo comparator | Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo. Receives: Drug: Placebo |
| MAD PTI-808 Active | Active comparator | Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo. Receives: Drug: PTI-808 |
| MAD PTI-808 Placebo | Placebo comparator | Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo. Receives: Drug: Placebo |
| FE PTI-808 Active | Active comparator | 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-808 |
| FE PTI-808 Placebo | Placebo comparator | 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: Placebo |
| Part 2 PTI-808 + PTI-801 + PTI-428 Active | Experimental | One cohort is planned where subjects will be randomized to either the triple active arm (dosed with PTI 808+PTI 801+PTI 428) OR placebo arm. Receives: Drug: PTI-808; Drug: PTI-428; Drug: PTI-801 |
| Part 2 matching Placebos | Placebo comparator | In all three cohorts in part 2, subjects will be randomized to active drug or placebo. The placebo arm for all cohorts consists of placebo capsules matching PTI-808+PTI-801+PTI-428. Receives: Drug: Placebo |
| Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo | Experimental | One cohort is planned where subjects are randomized to either 808 placebo + dual active arm (dosed with placebo matching PTI 808 plus PTI 801 + PTI 428) OR placebo arm. Receives: Drug: Placebo; Drug: PTI-428; Drug: PTI-801 |
| Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo | Active comparator | One cohort is planned where subjects are randomized to either 428 placebo + dual active arm (dosed with placebo matching PTI 428 plus PTI 808 and PTI 801) OR placebo arm. Receives: Drug: PTI-808; Drug: Placebo; Drug: PTI-801 |
| Part 3 CF MAD PTI-808 + PTI-801 + PTI-428 | Active comparator | In all cohorts in Part 3, subjects will be will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28. Receives: Drug: PTI-808; Drug: PTI-428; Drug: PTI-801 |
| Part 3 CF MAD PTI-808 placebo+PTI-801 placebo+PTI-428 placebo | Placebo comparator | In all cohorts in Part 3, subjects will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28. Receives: Drug: Placebo |
| Part 4 CF PTI-808 + PTI-801 + PTI-428 | Active comparator | In cohorts 3 \& 4 subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42. Receives: Drug: PTI-808; Drug: PTI-428; Drug: PTI-801 |
| Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo | Active comparator | In cohorts 3 \& 4, subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42. Receives: Drug: PTI-808; Drug: PTI-801 |
| Part 4 CF PTI-808 placebo + PTI-801 placebo + PTI-428 placebo | Placebo comparator | In cohorts 3 \& 4, subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42. 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: Adverse Events
Safety and tolerability measure by number of subjects who experience adverse events
Measured: Baseline to up to 14 days
Part 1 SAD and MAD: Physical Exams
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations
Measured: Baseline to up to 14 days
Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in vital signs
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in vital signs
Measured: Baseline to up to 14 days
Part 1 SAD and MAD: ECGs
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs
Measured: Baseline to up to 14 days
Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in safety labs
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs
Measured: Baseline to up to 14 days
Part 1 SAD and FE: terminal half life
Apparent terminal half-life (t1/2) of single oral dose
Measured: Through 72 hours post dose
Part 1 SAD and FE : Tmax
Time to reach maximum plasma concentration (Tmax) of single oral dose
Measured: Through 72 hours post dose
Part 1 SAD and FE: Cmax
Maximum plasma concentration (Cmax) of single oral dose
Measured: Through 72 hours post dose
Part 1 SAD : AUC
Area under the concentration-time curve from time 0 to 24 hours post dose (AUC 0-24) of single oral dose
Measured: Through 24 hours post dose
Part 1 SAD and FE: AUC0
AUC from time 0 to time of last measurable concentration (AUC0-last) of single oral dose
Measured: Through 72 hours post dose
Part 1 SAD and FE: AUC0-inf
AUC from time 0 to infinity (AUC0-inf) of single dose
Measured: Through 72 hours post dose
Part 1 MAD: t1/2
t1/2 of multiple oral dose
Measured: Through 72 hours post dose
Part 1 MAD: Tmax
Tmax of multiple oral doses
Measured: Through 72 hours post dose
Part 1 MAD: Cmax
Cmax of multiple oral doses
Measured: Through 72 hours post last dose
Part 1 MAD: AUC0-24
AUC0-24 of multiple oral dose
Measured: Through 24 hours post last dose
Part 1 MAD: AUC0-last
AUC0-last of multiple oral doses
Measured: Through 72 hours post last dose
Part 1 MAD: Urine
Cumulative amount of PTI-808 excreted unchanged in urine (Ae) as appropriate of multiple oral doses
Measured: Through 24 hours post last dose
Part 1 MAD: CLR
Renal clearance (CLR) of multiple oral doses
Measured: Through 24 hours post dose
Part 2: Physical Exams
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations
Measured: Baseline up to 14 days
Part 2: ECGs
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs
Measured: Baseline up to 14 days
Part 2: Safety Labs
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs
Measured: Baseline up to 14 days
Part 2: Vitals Signs
Measure by number of subjects who experience potential clinically significant changes in vital signs
Measured: Baseline up to 14 days
Part 3 CF: Physical Exams
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
Measured: Baseline up to 28 days
Part 3 CF: ECGs
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs
Measured: Baseline up to 28 days
Part 3 CF: Safety Labs
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs
Measured: Baseline up to 28 days
Part 3 CF: Vital Signs
Measured by number of subjects who experience potential clinically significant changes in vital signs
Measured: Baseline up to 28 days
Part 4 CF: Physical Exams
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
Measured: Baseline up to 42 days
Part 4 CF: ECGs
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs
Measured: Baseline up to 42 days
Part 4 CF: Safety Labs
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs
Measured: Baseline up to 42 days
Part 4 CF: Vital Signs
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
Measured: Baseline up to 42 days
Secondary outcomes (14)
Part 2: Apparent terminal half life (t1/2) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
Measured: Day 1 through Day 10
Part 2: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
Measured: Day 1 through Day 10
Part 2: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
Measured: Day 1 through Day 10
Part 2: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428
Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
Measured: Day 1 through Day 10
Part 2: AUC from time 0 to infinity (AUC0-inf) of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428
Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
Measured: Day 1 through Day 10
Part 3 CF: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF
Measured: Day 1 through Day 22
Part 3 CF: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF
Measured: Day 1 through Day 22
Part 3 CF: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428
Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF
Measured: Day 1 through Day 22
Part 3 CF: FEV1
Change in forced expiratory volume in one second (FEV1) over time
Measured: Baseline through Day 28
Part 4 CF: Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428
Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or with out PTI 428 in adults with CF
Measured: Day 1 through Day 28
Part 4 CF: Maximum plasma concentration (Cmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428
Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or with out PTI 428 in adults with CF
Measured: Day 1 through 28
Part 4 CF: AUC0-last of multiple oral doses when PTI 808 + PTI 801 is coadministered with or without PTI 428 in adults with CF
Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or without PTI 428 in adults with CF
Measured: Day 1 through 28
Part 4 CF: FEV1
Change in forced expiratory volume in one second (FEV1) over time
Measured: Baseline through Day 42
Part 4 CF Sweat Chloride
Change in sweat chloride concentrations over time
Measured: Baseline through Day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2017
- Study start17 Jul 2017
- Primary completion23 Dec 2019
- Study completion23 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy Volunteer - CompleteStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 179 participants (actual)
Sponsor and investigators
- Lead sponsor
- Proteostasis Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Cassandra Key, MD, Principal investigator, ICON Early Phase Services (Parts 1 & 2)Patrick Flume, MD, Principal investigator, Medical University of South Carolina (Parts 3 & 4)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03251092
- Sponsor's protocol ID
- PTI-808-01
- Status last verified
- Apr 2020
- First submitted
- 7 Aug 2017
- Last updated
- 22 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 22 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PTI-808 in Healthy Adult Subjects and in Adults With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT03251092
- Acronym / sponsor ID
- PTI-808-01
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 179 participants (actual)
- Lead sponsor
- Proteostasis Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 17 Jul 2017 (actual)
- Primary completion
- 23 Dec 2019 (actual)
- Study completion
- 23 Dec 2019 (actual)
- First posted
- 16 Aug 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.
Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD), multiple ascending dose (MAD), and Food Effect (FE) treatment groups.
The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and will be followed for 7 days post dose. A safety review committee (SRC) will convene after the completion of each cohort to evaluate safety and pharmacokinetic (PK) data.
Following the conclusion of the respective SAD level dose groups and after sufficient review of study data and approval by the SRC, a second set of healthy adult subjects will participate in an assigned MAD treatment group. The MAD treatment group is comprised of 3 ascending dose level cohorts where subjects will be randomized to receive either PTI-808 or placebo daily for 7 days and will be followed for 7 days after receiving the last dose.
Also following the conclusion of the respective SAD level dose groups, healthy adult subjects will participate in the FE treatment group.
Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive days.
Part 3 will enroll adult subjects with cystic fibrosis (CF) into a MAD treatment group consisting of 2 cohorts. Subjects will receive PTI-808 co-administered with PTI-801 and PTI-428. PTI-808 will be administered daily for 7 consecutive days followed by PTI-808 + PTI-801 + PTI-428 administered daily for 14 consecutive days.
Part 4 will enroll adult subjects with cystic fibrosis (CF) into 28-day cohorts. Subjects will receive PTI-808 co-administered with PTI-801 with or without PTI-428 versus matching placebo.
Detailed description
Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD), multiple ascending dose (MAD), and Food Effect (FE) treatment groups.
The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and will be followed for 7 days post dose.
The MAD treatment group is comprised of 3 ascending dose level cohorts where subjects will be randomized to receive either PTI-808 or placebo daily for 7 days and will be followed for 7 days after receiving the last dose.
Following the conclusion of the respective SAD level dose groups the food effect portion of the study will be initiated and subjects will be randomized to receive an initial single dose of PTI-808 either after an overnight fast of at least 10 hours (fasted group) or after an overnight fast of at least 10 hours followed the consumption of a high fat high calorie meal (fed group). After a 10 day washout period, subjects will cross over to the opposite group and receive a second dose of PTI-808. Subjects will be followed for up to 7 days following dosing.
Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive days.
Part 3 - Part 3 will enroll adult subjects with CF to assess the safety, tolerability, and PK of multiple ascending doses of PTI-808 co-administered with PTI-801 and PTI-428. Subjects will receive 7 days of PTI-808 or placebo followed by 14 days of PTI-808 or placebo co-administered with PTI-801+PTI-428 or matching placebos.
Part 4 - Part 4 will assess the safety, tolerability, PK, and the effects of PTI-808 co-administered with PTI-801 with or without PTI-428 over a 28-day treatment period in CF subjects who are either homozygous for the F508del CFTR genotype or are heterozygous for the F508del CFTR genotype. Subjects will be randomized to receive treatment with PTI-808 co-administered with PTI-801 with or without PTI-428 versus matching placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| SAD PTI-808 Active | Active comparator | Drug: PTI-808Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo. |
| SAD PTI-808 Placebo | Placebo comparator | Drug: PlaceboThree cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo. |
| MAD PTI-808 Active | Active comparator | Drug: PTI-808Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo. |
| MAD PTI-808 Placebo | Placebo comparator | Drug: PlaceboThree cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo. |
| FE PTI-808 Active | Active comparator | Drug: PTI-808Subjects will be randomized to Fed or Fasted on Days 1 and 12. Follow up visits will occur 7 days post Day 12 dose. |
| FE PTI-808 Placebo | Placebo comparator | Drug: PlaceboSubjects will be randomized to Fed or Fasted on Days 1 and 12. Follow up visits will occur 7 days post Day 12 dose. |
| Part 2 PTI-808 + PTI-801 + PTI-428 Active | Experimental | Drug: PTI-808, Drug: PTI-428, Drug: PTI-801One cohort is planned where subjects will be randomized to either the triple active arm (dosed with PTI 808+PTI 801+PTI 428) OR placebo arm. |
| Part 2 matching Placebos | Placebo comparator | Drug: PlaceboIn all three cohorts in part 2, subjects will be randomized to active drug or placebo. The placebo arm for all cohorts consists of placebo capsules matching PTI-808+PTI-801+PTI-428. |
| Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo | Experimental | Drug: Placebo, Drug: PTI-428, Drug: PTI-801One cohort is planned where subjects are randomized to either 808 placebo + dual active arm (dosed with placebo matching PTI 808 plus PTI 801 + PTI 428) OR placebo arm. |
| Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo | Active comparator | Drug: PTI-808, Drug: Placebo, Drug: PTI-801One cohort is planned where subjects are randomized to either 428 placebo + dual active arm (dosed with placebo matching PTI 428 plus PTI 808 and PTI 801) OR placebo arm. |
| Part 3 CF MAD PTI-808 + PTI-801 + PTI-428 | Active comparator | Drug: PTI-808, Drug: PTI-428, Drug: PTI-801In all cohorts in Part 3, subjects will be will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28. |
| Part 3 CF MAD PTI-808 placebo+PTI-801 placebo+PTI-428 placebo | Placebo comparator | Drug: PlaceboIn all cohorts in Part 3, subjects will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28. |
| Part 4 CF PTI-808 + PTI-801 + PTI-428 | Active comparator | Drug: PTI-808, Drug: PTI-428, Drug: PTI-801In cohorts 3 \& 4 subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42. |
| Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo | Active comparator | Drug: PTI-808, Drug: PTI-801In cohorts 3 \& 4, subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42. |
| Part 4 CF PTI-808 placebo + PTI-801 placebo + PTI-428 placebo | Placebo comparator | Drug: PlaceboIn cohorts 3 \& 4, subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42. |
Who may qualify
- Ages
- 18 to 99 years
- 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-808Active | Drug | FE PTI-808 Active, MAD PTI-808 Active, Part 2 PTI-808 + PTI-801 + PTI-428 Active, Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo, Part 3 CF MAD PTI-808 + PTI-801 + PTI-428, Part 4 CF PTI-808 + PTI-801 + PTI-428, Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo, SAD PTI-808 Active |
| PlaceboPlacebo | Drug | FE PTI-808 Placebo, MAD PTI-808 Placebo, Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo, Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo, Part 2 matching Placebos, Part 3 CF MAD PTI-808 placebo+PTI-801 placebo+PTI-428 placebo, Part 4 CF PTI-808 placebo + PTI-801 placebo + PTI-428 placebo, SAD PTI-808 Placebo |
| PTI-428Active | Drug | Part 2 PTI-808 + PTI-801 + PTI-428 Active, Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo, Part 3 CF MAD PTI-808 + PTI-801 + PTI-428, Part 4 CF PTI-808 + PTI-801 + PTI-428 |
| PTI-801Active | Drug | Part 2 PTI-808 + PTI-801 + PTI-428 Active, Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo, Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo, Part 3 CF MAD PTI-808 + PTI-801 + PTI-428, Part 4 CF PTI-808 + PTI-801 + PTI-428, Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo |
Primary outcome
Part 1 SAD and MAD: Adverse Events
Time frame: Baseline to up to 14 days
Safety and tolerability measure by number of subjects who experience adverse events
Part 1 SAD and MAD: Physical Exams
Time frame: Baseline to up to 14 days
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations
Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in vital signs
Time frame: Baseline to up to 14 days
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in vital signs
Part 1 SAD and MAD: ECGs
Time frame: Baseline to up to 14 days
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs
Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in safety labs
Time frame: Baseline to up to 14 days
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs
Part 1 SAD and FE: terminal half life
Time frame: Through 72 hours post dose
Apparent terminal half-life (t1/2) of single oral dose
Part 1 SAD and FE : Tmax
Time frame: Through 72 hours post dose
Time to reach maximum plasma concentration (Tmax) of single oral dose
Part 1 SAD and FE: Cmax
Time frame: Through 72 hours post dose
Maximum plasma concentration (Cmax) of single oral dose
Part 1 SAD : AUC
Time frame: Through 24 hours post dose
Area under the concentration-time curve from time 0 to 24 hours post dose (AUC 0-24) of single oral dose
Part 1 SAD and FE: AUC0
Time frame: Through 72 hours post dose
AUC from time 0 to time of last measurable concentration (AUC0-last) of single oral dose
Part 1 SAD and FE: AUC0-inf
Time frame: Through 72 hours post dose
AUC from time 0 to infinity (AUC0-inf) of single dose
Part 1 MAD: t1/2
Time frame: Through 72 hours post dose
t1/2 of multiple oral dose
Part 1 MAD: Tmax
Time frame: Through 72 hours post dose
Tmax of multiple oral doses
Part 1 MAD: Cmax
Time frame: Through 72 hours post last dose
Cmax of multiple oral doses
Part 1 MAD: AUC0-24
Time frame: Through 24 hours post last dose
AUC0-24 of multiple oral dose
Part 1 MAD: AUC0-last
Time frame: Through 72 hours post last dose
AUC0-last of multiple oral doses
Part 1 MAD: Urine
Time frame: Through 24 hours post last dose
Cumulative amount of PTI-808 excreted unchanged in urine (Ae) as appropriate of multiple oral doses
Part 1 MAD: CLR
Time frame: Through 24 hours post dose
Renal clearance (CLR) of multiple oral doses
Part 2: Physical Exams
Time frame: Baseline up to 14 days
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations
Part 2: ECGs
Time frame: Baseline up to 14 days
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs
Part 2: Safety Labs
Time frame: Baseline up to 14 days
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs
Part 2: Vitals Signs
Time frame: Baseline up to 14 days
Measure by number of subjects who experience potential clinically significant changes in vital signs
Part 3 CF: Physical Exams
Time frame: Baseline up to 28 days
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
Part 3 CF: ECGs
Time frame: Baseline up to 28 days
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs
Part 3 CF: Safety Labs
Time frame: Baseline up to 28 days
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs
Part 3 CF: Vital Signs
Time frame: Baseline up to 28 days
Measured by number of subjects who experience potential clinically significant changes in vital signs
Part 4 CF: Physical Exams
Time frame: Baseline up to 42 days
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
Part 4 CF: ECGs
Time frame: Baseline up to 42 days
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs
Part 4 CF: Safety Labs
Time frame: Baseline up to 42 days
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs
Part 4 CF: Vital Signs
Time frame: Baseline up to 42 days
Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
14 secondary outcomes
Part 2: Apparent terminal half life (t1/2) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Time frame: Day 1 through Day 10
Part 2: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Time frame: Day 1 through Day 10
Part 2: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Time frame: Day 1 through Day 10
Part 2: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428
Time frame: Day 1 through Day 10
Part 2: AUC from time 0 to infinity (AUC0-inf) of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428
Time frame: Day 1 through Day 10
Part 3 CF: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Time frame: Day 1 through Day 22
Part 3 CF: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Time frame: Day 1 through Day 22
Part 3 CF: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428
Time frame: Day 1 through Day 22
Part 3 CF: FEV1
Time frame: Baseline through Day 28
Part 4 CF: Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428
Time frame: Day 1 through Day 28
Part 4 CF: Maximum plasma concentration (Cmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428
Time frame: Day 1 through 28
Part 4 CF: AUC0-last of multiple oral doses when PTI 808 + PTI 801 is coadministered with or without PTI 428 in adults with CF
Time frame: Day 1 through 28
Part 4 CF: FEV1
Time frame: Baseline through Day 42
Part 4 CF Sweat Chloride
Time frame: Baseline through Day 42
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 22 Apr 2020.
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.
Cassandra Key, MD principal investigator
ICON Early Phase Services (Parts 1 & 2)
Patrick Flume, MD principal investigator
Medical University of South Carolina (Parts 3 & 4)
48 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PTI-808, PTI-428 and PTI-801 in people with Healthy Volunteer - Complete and Cystic Fibrosis - Complete, run by Proteostasis Therapeutics, Inc. at 48 sites in 9 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 22 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 48 sites in United States, France, United Kingdom, Germany, Canada and 4 more countries. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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: Adverse Events (time frame: Baseline to up to 14 days). The study lists 30 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 22 Apr 2020; AzTrials last refreshed its copy on 31 Oct 2026.