ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03500263
Recruitment Status : Recruiting
First Posted : April 17, 2018
Last Update Posted : August 23, 2018
Sponsor:
Information provided by (Responsible Party):
Proteostasis Therapeutics, Inc.

Brief Summary:
The study is a randomized, double-blind, placebo-controlled, study that will be conducted at multiple centers in subjects with Cystic Fibrosis (CF) who are homozygous for the F508del mutation.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: PTI-808 Drug: Placebo Drug: PTI-801 Drug: PTI-428 Phase 1

Detailed Description:
Study PTI-808-02 will enroll up to approximately 32 subjects. Subjects in the first cohort will receive PTI-808 and PTI-801. Following completion of Cohort 1, initiation of enrollment into subsequent cohorts will be based upon review and approval by the Safety Review Committee (SRC).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study Designed to Evaluate the Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis
Actual Study Start Date : January 30, 2018
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : November 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Active Comparator: Cohorts 1 and 2: PTI-808 Active Co-admin with PTI-801 Active
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
Drug: PTI-808
Active

Drug: PTI-801
Active

Placebo Comparator: Cohorts 1 and 2: PTI-808 Placebo Co-admin with PTI-801 Placebo
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
Drug: Placebo
Placebo

Active Comparator: Cohort 3 PTI-808 Active + PTI-801 Active + PTI-428 Active
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
Drug: PTI-808
Active

Drug: PTI-801
Active

Drug: PTI-428
Active

Placebo Comparator: Cohort 3 PTI-808 placebo + PTI-801 Placebo + PTI-428 Placebo
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
Drug: Placebo
Placebo

Drug: Placebo
Placebo

Active Comparator: Cohort 4 PTI-808 Active + PTI-801 Active + PTI-428 Active
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for 7 days immediately followed by PTI-808 co-administered with PTI-801 or placebos once-a-day for 7 days. A follow-up visit will occur on Day 21.
Drug: PTI-808
Active

Drug: PTI-801
Active

Drug: PTI-428
Active

Placebo Comparator: Cohort 4 PTI-808 Placebo + PTI-801 Placebo + PTI-428 Placebo
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for 7 days immediately followed by PTI-808 co-administered with PTI-801 or placebos once-a-day for 7 days. A follow-up visit will occur on Day 21.
Drug: Placebo
Placebo

Drug: Placebo
Placebo




Primary Outcome Measures :
  1. Safety and tolerability measured by the number of subjects who experience adverse events and potentially significant clinical laboratory assessments, electrocardiography, physical examinations, vital signs. [ Time Frame: Baseline through Day 21 ]

Secondary Outcome Measures :
  1. Apparent terminal half-life (t1/2) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only) [ Time Frame: Day 1 through 15 ]
  2. Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only) [ Time Frame: Day 1 through 15 ]
  3. Maximum plasma concentration (Cmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only) [ Time Frame: Day 1 through 15 ]

Other Outcome Measures:
  1. Change in FEV1 over time [ Time Frame: Baseline through Day 21 ]
  2. Change in sweat chloride over time [ Time Frame: Baseline through Day 21 ]
  3. Change in nasal epithelial mRNA expression over time [ Time Frame: Baseline through Day 21 ]
  4. Change in nasal protein expression over time [ Time Frame: Baseline through Day 21 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of CF with the F508del/F508del genotype on record, along with clinical findings consistent with CF such as chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities
  • Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive
  • Non-smoker and non-tobacco user for a minimum of 30 days prior to screening

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03500263


Contacts
Contact: Proteostasis Clinical Trials 1-866-223-3262 pticlinicaltrials@proteostasis.com

Locations
United Kingdom
Celerion Recruiting
Belfast, United Kingdom, BT9 6AD
Queen Elizabeth University Hospital Recruiting
Glasgow, United Kingdom, G514TF
Medicines Evaluation Unit Recruiting
Manchester, United Kingdom
Sponsors and Collaborators
Proteostasis Therapeutics, Inc.

Additional Information:
Responsible Party: Proteostasis Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03500263     History of Changes
Other Study ID Numbers: PTI-808-02
First Posted: April 17, 2018    Key Record Dates
Last Update Posted: August 23, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases