Clinical trial NCT02955888: Study of Safety, Tolerability & Efficacy in Cystic Fibrosis Patients With Abnormal Glucose Tolerance
Official title: A Phase 2, Double-Blind, Placebo Controlled Study to Evaluate the Safety & Tolerability of PBI-4050 and Its Effects on Pancreatic and Pulmonary Function in Cystic Fibrosis Patients With Abnormal Glucose Tolerance
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Liminal BioSciences Ltd.
Sponsor class: INDUSTRY
First posted: 2016-11-04
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, multi-center, double blind, placebo controlled study to evaluate the safety and tolerability of PBI-4050, and its effects on the pancreatic, pulmonary functions and on various biomarkers in Cystic Fibrosis patients with abnormal glucose tolerance. Patients with abnormal glucose tolerance have elevated glucose level either at 1 hour or 2 hour during an Oral Glucose Tolerance Test (OGTT). The Main study will include 24 weeks of treatment with PBI-4050 or matching placebo. At the end of the treatment period, patients will have the option of participating in a 24-week Extension study.

Detailed description: This is a Phase 2, multi-center, double blind, placebo controlled study to evaluate the safety and tolerability of PBI-4050, and its effects on the pancreatic, pulmonary functions and on various biomarkers in Cystic Fibrosis patients with abnormal glucose tolerance. Patients with abnormal glucose tolerance have elevated glucose level either at 1 hour or 2 hour during an Oral Glucose Tolerance Test (OGTT).

A total of 90 patients will be enrolled for study participation. A Data Safety Monitoring Board (DSMB) will continually review individual patients safety data obtained from the 90 patients. When the first 15 patients have completed at least 1 month of study treatment, the DSMB will meet formally to determine whether additional patients may be enrolled, the study should continue with changes or if the study should be stopped. In addition, the DSMB will review the PK data and may recommend dose adjustment based on the PK results.

The total duration of study participation for each patient is at least 32 weeks, including up to 4 weeks of a screening period, 24 weeks of study treatment and 4 weeks of safety follow-up.

Patients who choose to participate in the open label extension will be in the study for an additional 24 weeks of study treatment and 4 weeks of safety follow-up (for a total of 56 weeks).

Eligibility criteria: Inclusion Criteria:

1. Patient is 18 years of age or older at screening.
2. Patient has a documented and confirmed CF diagnosis.
3. Patient has performed an OGTT for diagnosis of INDENT, IGT and de novo CFRD within 12 months prior to screening visit.
4. Patient has a Body Mass Index (BMI) of at least 17 kg/m2.
5. Patient has signed written informed consent.
6. Patient is able and willing to self-monitor blood glucose level at home.
7. Female patients of childbearing potential must have a negative pregnancy test (serum or urine) and agree to use adequate birth control from screening throughout the study and for the 30 days after the last study drug administration.
8. If a male patient has not been vasectomized at least 6 months before screening and partners with a woman of childbearing potential, he must be willing to use an acceptable contraceptive method throughout the study and for the 30 days after the last study drug administration.

Exclusion Criteria:

1. Patient has recent or ongoing infection requiring intravenous treatment with an anti-infective agent within 30 days before screening.
2. Patient is concurrently taking high dose of ibuprofen (\>30 mg/kg) or is using corticosteroids (except inhaled and topical corticosteroids).
3. Patient is currently using weight-loss medications.
4. 4. Patient has used any moderate/potent inhibitor of cytochrome P450 (CYP) 2C9 isozyme or strong inhibitor of CYP3A isozyme within 30 days prior to the first study drug administration.
5. Patient has significantly elevated liver enzyme levels, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 Upper Limit of Normal (ULN) or total bilirubin above ULN at screening.
6. Patient has a history of chronic alcohol or other substance abuse as determined at screening that may prevent study compliance based on Investigator judgment.
7. History of malignancy of any organ system, treated or untreated, within the past 5 years other than basal or squamous cell skin cancer.
8. Patient has unstable chronic heart failure that has required change in therapy within 2 months prior to screening.
9. Patient with known non-controlled history of infection with Human Immunodeficiency Virus (HIV) and/or active Hepatitis.
10. Woman who is pregnant, breast-feeding or planning a pregnancy during the course of the study.
11. Woman of childbearing potential who is unwilling to use adequate birth control throughout the duration of the study.
12. Patient has any condition that, in the Investigator's opinion, is likely to interfere with study conduct and compliance.
13. Patient has participated in an investigational clinical trial within 30 days (or 5 half-lives, whichever is longer) prior to screening visit.
14. Patient is under insulin and/or repaglinide treatment at screening/baseline

Primary outcomes:
measure: Number of Subjects with Adverse Events (Combined Main Study and Extension Study Participation)
timeFrame: Baseline to 1 Year
Secondary outcomes:
measure: Change from Baseline in glucose level following Oral Glucose Tolerance Test (OGTT) (Combined Main Study and Extension Study Participation)
timeFrame: Up to 1 Year
measure: Change from Baseline of insulin-secretion following Oral Glucose Tolerance Test (OGTT) (Combined Main Study and Extension Study Participation)
timeFrame: Up 1 Year
measure: Change from Baseline of HbA1C following Oral Glucose Tolerance Test (OGTT) (Combined Main Study and Extension Study Participation)
timeFrame: Up to 1 Year
measure: Change from Baseline in pulmonary function parameters (FEV1 ) (Combined Main Study and Extension Study Participation)
timeFrame: Up to 1 Year
measure: Change from Baseline in pulmonary function parameters ( FVC) (Combined Main Study and Extension Study Participation)
timeFrame: Up to 1 Year
measure: Change from Baseline in pulmonary function parameters (FEV1/FVC ratio) (Combined Main Study and Extension Study Participation)
timeFrame: Up to 1 Year
measure: Change from Baseline in pulmonary function parameters (Forced Expiratory Flow (FEF25%-75%)) (Combined Main Study and Extension Study Participation)
timeFrame: Up to 1 Year
measure: Change from baseline in weight (Combined Main Study and Extension Study Participation)
timeFrame: Up to1 Year
Other outcomes:
measure: Changes from baseline in fibrotic and inflammatory biomarkers in blood (Combined Main Study and Extension Study Participation)
timeFrame: Up to 1 Year
measure: Changes from baseline in fibrotic and inflammatory biomarkers in urine (Combined Main Study and Extension Study Participation)
timeFrame: Up to1 Year
Locations:
city: Vancouver
country: Canada
facility: St. Paul's Hospital - Pacific Lung Health Centre (PLHC)
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Science Center
state: Nova Scotia
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: Institut de Recherches Cliniques de Montréal (IRCM)
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Quebec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval (IUCPQ)
Study officials:
affiliation: Liminal BioSciences Ltd.
name: John Moran, MD
role: STUDY_CHAIR
References: