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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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]

PTI-808-01

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Healthy Volunteer - Complete

Cystic Fibrosis - Complete

Condition category

Condition code

Human Genetics and Inherited Disorders

Cystic fibrosis

Respiratory

Other respiratory disorders / diseases

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Inflammatory and Immune System

Connective tissue diseases

Inflammatory and Immune System

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]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Part 1 SAD and MAD: Adverse Events

Timepoint [1]

Baseline to up to 14 days

Primary outcome [2]

Part 1 SAD and MAD: Physical Exams

Timepoint [2]

Baseline to up to 14 days

Primary outcome [3]

Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in vital signs

Timepoint [3]

Baseline to up to 14 days

Primary outcome [4]

Part 1 SAD and MAD: ECGs

Timepoint [4]

Baseline to up to 14 days

Primary outcome [5]

Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in safety labs

Timepoint [5]

Baseline to up to 14 days

Primary outcome [6]

Part 1 SAD and FE: terminal half life

Timepoint [6]

Through 72 hours post dose

Primary outcome [7]

Part 1 SAD and FE : Tmax

Timepoint [7]

Through 72 hours post dose

Primary outcome [8]

Part 1 SAD and FE: Cmax

Timepoint [8]

Through 72 hours post dose

Primary outcome [9]

Part 1 SAD : AUC

Timepoint [9]

Through 24 hours post dose

Primary outcome [10]

Part 1 SAD and FE: AUC0

Timepoint [10]

Through 72 hours post dose

Primary outcome [11]

Part 1 SAD and FE: AUC0-inf

Timepoint [11]

Through 72 hours post dose

Primary outcome [12]

Part 1 MAD: t1/2

Timepoint [12]

Through 72 hours post dose

Primary outcome [13]

Part 1 MAD: Tmax

Timepoint [13]

Through 72 hours post dose

Primary outcome [14]

Part 1 MAD: Cmax

Timepoint [14]

Through 72 hours post last dose

Primary outcome [15]

Part 1 MAD: AUC0-24

Timepoint [15]

Through 24 hours post last dose

Primary outcome [16]

Part 1 MAD: AUC0-last

Timepoint [16]

Through 72 hours post last dose

Primary outcome [17]

Part 1 MAD: Urine

Timepoint [17]

Through 24 hours post last dose

Primary outcome [18]

Part 1 MAD: CLR

Timepoint [18]

Through 24 hours post dose

Primary outcome [19]

Part 2: Physical Exams

Timepoint [19]

Baseline up to 14 days

Primary outcome [20]

Part 2: ECGs

Timepoint [20]

Baseline up to 14 days

Primary outcome [21]

Part 2: Safety Labs

Timepoint [21]

Baseline up to 14 days

Primary outcome [22]

Part 2: Vitals Signs

Timepoint [22]

Baseline up to 14 days

Primary outcome [23]

Part 3 CF: Physical Exams

Timepoint [23]

Baseline up to 28 days

Primary outcome [24]

Part 3 CF: ECGs

Timepoint [24]

Baseline up to 28 days

Primary outcome [25]

Part 3 CF: Safety Labs

Timepoint [25]

Baseline up to 28 days

Primary outcome [26]

Part 3 CF: Vital Signs

Timepoint [26]

Baseline up to 28 days

Primary outcome [27]

Part 4 CF: Physical Exams

Timepoint [27]

Baseline up to 42 days

Primary outcome [28]

Part 4 CF: ECGs

Timepoint [28]

Baseline up to 42 days

Primary outcome [29]

Part 4 CF: Safety Labs

Timepoint [29]

Baseline up to 42 days

Primary outcome [30]

Part 4 CF: Vital Signs

Timepoint [30]

Baseline up to 42 days

Secondary outcome [1]

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]

Day 1 through Day 10

Secondary outcome [2]

Part 2: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428

Timepoint [2]

Day 1 through Day 10

Secondary outcome [3]

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]

Day 1 through Day 10

Secondary outcome [4]

Part 2: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428

Timepoint [4]

Day 1 through Day 10

Secondary outcome [5]

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]

Day 1 through Day 10

Secondary outcome [6]

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]

Day 1 through Day 22

Secondary outcome [7]

Part 3 CF: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428

Timepoint [7]

Day 1 through Day 22

Secondary outcome [8]

Part 3 CF: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428

Timepoint [8]

Day 1 through Day 22

Secondary outcome [9]

Part 3 CF: FEV1

Timepoint [9]

Baseline through Day 28

Secondary outcome [10]

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]

Day 1 through Day 28

Secondary outcome [11]

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]

Day 1 through 28

Secondary outcome [12]

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]

Day 1 through 28

Secondary outcome [13]

Part 4 CF: FEV1

Timepoint [13]

Baseline through Day 42

Secondary outcome [14]

Part 4 CF Sweat Chloride

Timepoint [14]

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

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]

John Hunter Hospital - Lambton

Recruitment postcode(s) [1]

2305 - Lambton

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

Arizona

Country [2]

United States of America

State/province [2]

California

Country [3]

United States of America

State/province [3]

Colorado

Country [4]

United States of America

State/province [4]

Florida

Country [5]

United States of America

State/province [5]

Georgia

Country [6]

United States of America

State/province [6]

Illinois

Country [7]

United States of America

State/province [7]

Maryland

Country [8]

United States of America

State/province [8]

Massachusetts

Country [9]

United States of America

State/province [9]

Michigan

Country [10]

United States of America

State/province [10]

Minnesota

Country [11]

United States of America

State/province [11]

Missouri

Country [12]

United States of America

State/province [12]

Montana

Country [13]

United States of America

State/province [13]

Nebraska

Country [14]

United States of America

State/province [14]

New Hampshire

Country [15]

United States of America

State/province [15]

New York

Country [16]

United States of America

State/province [16]

North Carolina

Country [17]

United States of America

State/province [17]

Pennsylvania

Country [18]

United States of America

State/province [18]

South Carolina

Country [19]

United States of America

State/province [19]

Texas

Country [20]

United States of America

State/province [20]

Utah

Country [21]

Belgium

State/province [21]

Brussels

Country [22]

Belgium

State/province [22]

Leuven

Country [23]

Canada

State/province [23]

British Columbia

Country [24]

Canada

State/province [24]

Quebec

Country [25]

Canada

State/province [25]

Québec

Country [26]

Denmark

State/province [26]

Copenhagen

Country [27]

France

State/province [27]

Alpes-Maritimes

Country [28]

France

State/province [28]

Gironde

Country [29]

France

State/province [29]

Loire-Atlantique

Country [30]

France

State/province [30]

Marne

Country [31]

France

State/province [31]

Lyon

Country [32]

France

State/province [32]

Paris

Country [33]

Germany

State/province [33]

Berlin

Country [34]

Germany

State/province [34]

Cologne

Country [35]

Germany

State/province [35]

Essen

Country [36]

Germany

State/province [36]

Frankfurt

Country [37]

Germany

State/province [37]

München

Country [38]

New Zealand

State/province [38]

Auckland

Country [39]

United Kingdom

State/province [39]

Devon

Country [40]

United Kingdom

State/province [40]

Scotland

Country [41]

United Kingdom

State/province [41]

West Midlands

Country [42]

United Kingdom

State/province [42]

Belfast

Country [43]

United Kingdom

State/province [43]

London

Country [44]

United Kingdom

State/province [44]

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/study/NCT03251092

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Cassandra Key, MD

Address

ICON Early Phase Services (Parts 1 & 2)

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT03251092

Trial Review

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