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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03251092




Registration number
NCT03251092
Ethics application status
Date submitted
7/08/2017
Date registered
16/08/2017
Date last updated
22/04/2020

Titles & IDs
Public title
Study Designed to Assess the Safety, Tolerability and PK of PTI-808 in Healthy Volunteers and in Adults With Cystic Fibrosis
Scientific title
A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PTI-808 in Healthy Adult Subjects and in Adults With Cystic Fibrosis
Secondary ID [1] 0 0
PTI-808-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Volunteer - Complete 0 0
Cystic Fibrosis - Complete 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PTI-808
Treatment: Drugs - Placebo
Treatment: Drugs - PTI-428
Treatment: Drugs - PTI-801

Active Comparator: SAD PTI-808 Active - Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.

Placebo Comparator: SAD PTI-808 Placebo - Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.

Active Comparator: MAD PTI-808 Active - Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.

Placebo Comparator: MAD PTI-808 Placebo - Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.

Active Comparator: FE PTI-808 Active - Subjects will be randomized to Fed or Fasted on Days 1 and 12. Follow up visits will occur 7 days post Day 12 dose.

Placebo Comparator: FE PTI-808 Placebo - Subjects will be randomized to Fed or Fasted on Days 1 and 12. Follow up visits will occur 7 days post Day 12 dose.

Experimental: Part 2 PTI-808 + PTI-801 + PTI-428 Active - 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.

Placebo Comparator: Part 2 matching Placebos - 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.

Experimental: Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo - 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.

Active Comparator: Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo - 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.

Active Comparator: Part 3 CF MAD PTI-808 + PTI-801 + PTI-428 - 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.

Placebo Comparator: Part 3 CF MAD PTI-808 placebo+PTI-801 placebo+PTI-428 placebo - 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.

Active Comparator: Part 4 CF PTI-808 + PTI-801 + PTI-428 - 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.

Active Comparator: Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo - 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.

Placebo Comparator: Part 4 CF PTI-808 placebo + PTI-801 placebo + PTI-428 placebo - 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.


Treatment: Drugs: PTI-808
Active

Treatment: Drugs: Placebo
Placebo

Treatment: Drugs: PTI-428
Active

Treatment: Drugs: PTI-801
Active
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1 SAD and MAD: Adverse Events
Timepoint [1] 0 0
Baseline to up to 14 days
Primary outcome [2] 0 0
Part 1 SAD and MAD: Physical Exams
Timepoint [2] 0 0
Baseline to up to 14 days
Primary outcome [3] 0 0
Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in vital signs
Timepoint [3] 0 0
Baseline to up to 14 days
Primary outcome [4] 0 0
Part 1 SAD and MAD: ECGs
Timepoint [4] 0 0
Baseline to up to 14 days
Primary outcome [5] 0 0
Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in safety labs
Timepoint [5] 0 0
Baseline to up to 14 days
Primary outcome [6] 0 0
Part 1 SAD and FE: terminal half life
Timepoint [6] 0 0
Through 72 hours post dose
Primary outcome [7] 0 0
Part 1 SAD and FE : Tmax
Timepoint [7] 0 0
Through 72 hours post dose
Primary outcome [8] 0 0
Part 1 SAD and FE: Cmax
Timepoint [8] 0 0
Through 72 hours post dose
Primary outcome [9] 0 0
Part 1 SAD : AUC
Timepoint [9] 0 0
Through 24 hours post dose
Primary outcome [10] 0 0
Part 1 SAD and FE: AUC0
Timepoint [10] 0 0
Through 72 hours post dose
Primary outcome [11] 0 0
Part 1 SAD and FE: AUC0-inf
Timepoint [11] 0 0
Through 72 hours post dose
Primary outcome [12] 0 0
Part 1 MAD: t1/2
Timepoint [12] 0 0
Through 72 hours post dose
Primary outcome [13] 0 0
Part 1 MAD: Tmax
Timepoint [13] 0 0
Through 72 hours post dose
Primary outcome [14] 0 0
Part 1 MAD: Cmax
Timepoint [14] 0 0
Through 72 hours post last dose
Primary outcome [15] 0 0
Part 1 MAD: AUC0-24
Timepoint [15] 0 0
Through 24 hours post last dose
Primary outcome [16] 0 0
Part 1 MAD: AUC0-last
Timepoint [16] 0 0
Through 72 hours post last dose
Primary outcome [17] 0 0
Part 1 MAD: Urine
Timepoint [17] 0 0
Through 24 hours post last dose
Primary outcome [18] 0 0
Part 1 MAD: CLR
Timepoint [18] 0 0
Through 24 hours post dose
Primary outcome [19] 0 0
Part 2: Physical Exams
Timepoint [19] 0 0
Baseline up to 14 days
Primary outcome [20] 0 0
Part 2: ECGs
Timepoint [20] 0 0
Baseline up to 14 days
Primary outcome [21] 0 0
Part 2: Safety Labs
Timepoint [21] 0 0
Baseline up to 14 days
Primary outcome [22] 0 0
Part 2: Vitals Signs
Timepoint [22] 0 0
Baseline up to 14 days
Primary outcome [23] 0 0
Part 3 CF: Physical Exams
Timepoint [23] 0 0
Baseline up to 28 days
Primary outcome [24] 0 0
Part 3 CF: ECGs
Timepoint [24] 0 0
Baseline up to 28 days
Primary outcome [25] 0 0
Part 3 CF: Safety Labs
Timepoint [25] 0 0
Baseline up to 28 days
Primary outcome [26] 0 0
Part 3 CF: Vital Signs
Timepoint [26] 0 0
Baseline up to 28 days
Primary outcome [27] 0 0
Part 4 CF: Physical Exams
Timepoint [27] 0 0
Baseline up to 42 days
Primary outcome [28] 0 0
Part 4 CF: ECGs
Timepoint [28] 0 0
Baseline up to 42 days
Primary outcome [29] 0 0
Part 4 CF: Safety Labs
Timepoint [29] 0 0
Baseline up to 42 days
Primary outcome [30] 0 0
Part 4 CF: Vital Signs
Timepoint [30] 0 0
Baseline up to 42 days
Secondary outcome [1] 0 0
Part 2: Apparent terminal half life (t1/2) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Timepoint [1] 0 0
Day 1 through Day 10
Secondary outcome [2] 0 0
Part 2: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Timepoint [2] 0 0
Day 1 through Day 10
Secondary outcome [3] 0 0
Part 2: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Timepoint [3] 0 0
Day 1 through Day 10
Secondary outcome [4] 0 0
Part 2: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428
Timepoint [4] 0 0
Day 1 through Day 10
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Day 1 through Day 10
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Day 1 through Day 22
Secondary outcome [7] 0 0
Part 3 CF: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
Timepoint [7] 0 0
Day 1 through Day 22
Secondary outcome [8] 0 0
Part 3 CF: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428
Timepoint [8] 0 0
Day 1 through Day 22
Secondary outcome [9] 0 0
Part 3 CF: FEV1
Timepoint [9] 0 0
Baseline through Day 28
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
Day 1 through Day 28
Secondary outcome [11] 0 0
Part 4 CF: Maximum plasma concentration (Cmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428
Timepoint [11] 0 0
Day 1 through 28
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
Day 1 through 28
Secondary outcome [13] 0 0
Part 4 CF: FEV1
Timepoint [13] 0 0
Baseline through Day 42
Secondary outcome [14] 0 0
Part 4 CF Sweat Chloride
Timepoint [14] 0 0
Baseline through Day 42

Eligibility
Key inclusion criteria
Part 1 and Part 2

1. Adults aged 18 to 55 years old, inclusive, at the time of informed consent

2. Body mass index =18 and <30 kg/m2

3. Subject must be a non-smoker and non-tobacco user for a minimum of 30 days prior to
screening and for the duration of the study.

4. Subject understands the full nature and purpose of the study, including possible risks
and side effects, and is willing and able to comply with all compulsory study
procedures and provides informed consent/permission prior to any study procedures
being performed.

5. Females of childbearing potential and males capable of fathering a child must meet the
contraception requirements

Part 1 & Part 2
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History or current evidence of any clinically significant cardiac, endocrinologic,
hematologic, hepatobiliary, immunologic, metabolic, urologic, pulmonary, neurologic,
dermatologic, psychiatric, renal, or other major disease, as determined by the
investigator

2. Prolonged QT interval with Fridericia's correction >450 msec at screening

3. Abnormal liver function as defined by aspartate transaminase (AST), alanine
transaminase (ALT), or bilirubin >1.5× the upper limit of the normal range

4. Abnormal renal function at screening defined as creatinine clearance <90 mL/min using
the Cockroft-Gault equation

5. Clinically significant screening results that would exclude subject from the study
(e.g., medical histories, PE, ECGs, vital signs, and laboratory profiles) as deemed by
the investigator

6. Participation in another clinical study or treatment with an investigational agent
within 30 days or five half-lives, whichever is longer, prior to Study Day 1

7. History of cancer within the past 5 years (excluding non-melanoma skin cancer)

8. History or current evidence of alcohol or drug abuse or dependence within 12 months of
screening as determined by the investigator

9. Positive urine screen for prohibited drugs (cocaine, cannabinoids, nicotine [urine
cotinine is the detection mechanism for nicotine], opiates, barbiturates,
amphetamines, and benzodiazepines) or positive alcohol test at screening

10. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface
antigen (HBsAg), or hepatitis C virus antibody (HCVAb)

11. Clinically significant infection within 3 months of screening as determined by the
investigator

12. Known or suspected hypersensitivity or idiosyncratic reaction to study medication or
any components thereof

13. Has donated blood within 3 months of screening or plans to donate blood within 3
months of study completion

14. Pregnant or nursing women

15. Any conditions that, in the opinion of the investigator, would make the subject
unsuitable for enrollment or could interfere with the subject's participation in or
completion of the study

16. Use of prohibited medications within 14 days prior to dosing of study drug

Part 3 CF Inclusion Criteria:

1. Confirmed diagnosis of CF with the F508del/F508del genotype

2. Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive

3. Non-smoker and non-tobacco user for a minimum of 30 days prior to screening

Part 3 CF

1. Participation in another clinical trial or treatment with an investigational agent
within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1

2. History of cancer within the past 5 years (excluding cervical cancer in situ with
curative therapy for at least one year prior to screening and non-melanoma skin
cancer)

3. History of organ transplantation

4. Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically
significant infection or illness (as determined by the investigator) requiring an
increase or addition of medication, such as antibiotics or corticosteroids, within 14
days of Day 1

5. Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline,
azithromycin, Pulmozyme®, Cayston®, TOBI®)) or any change in chronic therapy
(excluding pancreatic enzyme replacement therapy) within 28 days prior to Day 1

6. History or current evidence of alcohol or drug abuse or dependence within 12 months of
screening as determined by the investigator

7. Pregnant or nursing women

8. Currently taking or has taken a CFTR modulator within 30 days prior to initial dose of
study drugs

Part 4 CF Inclusion Criteria:

1. Confirmed diagnosis of CF with either the F508del CFTR homozygous genotype on record
or for heterozygote subjects, only one copy of the F508del CFTR mutation on record

2. Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive

3. Non-smoker and non-tobacco user for a minimum of 30 days prior to screening

Part 4 CF

1. Participation in another clinical trial or treatment with an investigational agent
within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1

2. History of cancer within the past 5 years (excluding cervical cancer in situ with
curative therapy for at least one year prior to screening and non-melanoma skin
cancer)

3. History of organ transplantation

4. Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically
significant infection or illness (as determined by the investigator) requiring an
increase or addition of medication, such as antibiotics or corticosteroids, within 28
days of Day 1

5. Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline,
azithromycin, Pulmozyme®, Cayston®, TOBI®)) or any change in chronic therapy
(excluding pancreatic enzyme replacement therapy) within 28 days of Day 1

6. History or current evidence of alcohol or drug abuse or dependence within 12 months of
screening as determined by the investigator

7. Pregnant or nursing women

8. Currently taking or has taken a CFTR modulator within 14 days prior to the screening
visit

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/07/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/12/2019
Sample size
Target
Accrual to date
Final
179
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
John Hunter Hospital - Lambton
Recruitment postcode(s) [1] 0 0
2305 - Lambton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Montana
Country [13] 0 0
United States of America
State/province [13] 0 0
Nebraska
Country [14] 0 0
United States of America
State/province [14] 0 0
New Hampshire
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Utah
Country [21] 0 0
Belgium
State/province [21] 0 0
Brussels
Country [22] 0 0
Belgium
State/province [22] 0 0
Leuven
Country [23] 0 0
Canada
State/province [23] 0 0
British Columbia
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec
Country [25] 0 0
Canada
State/province [25] 0 0
Québec
Country [26] 0 0
Denmark
State/province [26] 0 0
Copenhagen
Country [27] 0 0
France
State/province [27] 0 0
Alpes-Maritimes
Country [28] 0 0
France
State/province [28] 0 0
Gironde
Country [29] 0 0
France
State/province [29] 0 0
Loire-Atlantique
Country [30] 0 0
France
State/province [30] 0 0
Marne
Country [31] 0 0
France
State/province [31] 0 0
Lyon
Country [32] 0 0
France
State/province [32] 0 0
Paris
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
Country [34] 0 0
Germany
State/province [34] 0 0
Cologne
Country [35] 0 0
Germany
State/province [35] 0 0
Essen
Country [36] 0 0
Germany
State/province [36] 0 0
Frankfurt
Country [37] 0 0
Germany
State/province [37] 0 0
München
Country [38] 0 0
New Zealand
State/province [38] 0 0
Auckland
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Devon
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Scotland
Country [41] 0 0
United Kingdom
State/province [41] 0 0
West Midlands
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Belfast
Country [43] 0 0
United Kingdom
State/province [43] 0 0
London
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Proteostasis Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03251092
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Cassandra Key, MD
Address 0 0
ICON Early Phase Services (Parts 1 & 2)
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03251092