Safety and Tolerability of PBI-4050 and Its Effects on the Biomarkers in Subjects With Alström Syndrome
Primary Purpose
Inflammation and Fibrosis, Diabetes
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
PBI-4050
Sponsored by
About this trial
This is an interventional treatment trial for Inflammation and Fibrosis
Eligibility Criteria
Inclusion Criteria :
- Subject is 16 years of age or older at screening.
- Subject has signed informed consent.
- Subject has a documented diagnosis of Alström syndrome
- Subject on diabetes treatment has been receiving the same antidiabetic agent(s) for a minimum of 1 month before screening.
- Subject is able and willing to self-monitor blood glucose level at home or can obtain adequate assistance from care givers.
- Female subjects of childbearing potential must have a negative serum pregnancy test at screening and agree to use adequate birth control from screening throughout the study and for 30 days after the last Investigational Medicinal Product (IMP) administration. If a male subject 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 30 days after the last IMP administration.
Exclusion Criteria:
- Subject has recent or on-going infection requiring systemic treatment with an anti-infective agent within 30 days before screening.
- Subject has had at least two documented episodes of severe hypoglycaemia within 12 months before screening
- Subject has uncontrolled hypertension with BP > 170/100 mmHg as determined at screening.
- Subject has alanine transaminase (ALT) or aspartate transaminase (AST) level ≥ 5 × upper limit of normal (ULN) at screening.
- Subject is currently using weight loss medications at screening. Subjects may be re-screened after stopping the weight loss medication for a period of at least 5 half-lives.
- Subject has used any moderate/potent inducer or inhibitor of CYP2C9 isozyme or strong inducer or inhibitor of cytochrome P450 (CYP) 3A isozyme within 30 days prior to the first study drug administration.
- Subject has a history of chronic alcohol or other substance abuse as determined at screening.
- Woman who is pregnant, breast-feeding, or planning a pregnancy during the course of the study as determined at screening.
- Subject has any condition that, in the investigator's opinion, is likely to interfere with study conduct and compliance
- Subject has a history of an allergic reaction to PBI-4050 or any of its excipients.
Sites / Locations
- University Hospitals Birmingham NHS Foundation Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PBI-4050
Arm Description
Four 200 mg capsules (total 800 mg) administered orally, once daily.
Outcomes
Primary Outcome Measures
Description and number of abnormal laboratory values and adverse events that are related to treatment.
Secondary Outcome Measures
Change from baseline in metabolic syndrome parameters over time.
Change from baseline in fasting plasma glucose over time. Change from baseline in fasting plasma insulin over time. Change from baseline in glycated hemoglobin (HbA1c) over time. Change from baseline in Homeostasis Model Assessment for steady state beta cell function (HOMA-B) and insulin sensitivity (HOMA-S) over time.
Change from baseline in biomarkers in blood and urine over time
Percentage of reduction and/or increase of level of biomarkers
Change from baseline in cardiac function parameter: NT-proBNP
Change from baseline of antidiabetic treatment
Dosing change, new medication added or treatment discontinuation
Full Information
NCT ID
NCT02739217
First Posted
February 25, 2016
Last Updated
August 28, 2018
Sponsor
Liminal BioSciences Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT02739217
Brief Title
Safety and Tolerability of PBI-4050 and Its Effects on the Biomarkers in Subjects With Alström Syndrome
Official Title
A Phase 2, Single-Arm, Open-Label Study to Evaluate the Safety and Tolerability of PBI-4050 and of Its Effects on the Inflammatory, Fibrosis, Diabetes and Obesity Biomarkers in Subjects With Alström Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
February 22, 2016 (Actual)
Primary Completion Date
September 26, 2017 (Actual)
Study Completion Date
June 4, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Liminal BioSciences Ltd.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase 2, single-centre, single-arm, open-label study of the safety, tolerability, and effects on biomarkers of PBI-4050 in subjects with Alström syndrome for a treatment duration of 24 weeks.
Subjects who complete the initial 24 weeks of treatment may continue treatment for an additional 36 or 48 weeks, provided the subject signs informed consent.
Detailed Description
This is a Phase 2, single-centre, single-arm, open-label study of the safety, tolerability, and effects on biomarkers of PBI-4050 in subjects with Alström syndrome. Approximately 18 subjects will be enrolled. The duration of study participation is approximately 35 weeks for each subject and comprises of 9 on site visits and telephone contacts in between visits.
Subjects who complete the initial 24 weeks of treatment may continue treatment for an additional 36 or 48 weeks (Extension Period [EP]), provided the subject signs informed consent. The extension period includes a further 3 on site visits and telephone contacts in between visits. The total duration of the study participation is extended to approximately 71 or 83 weeks. The Data Safety Monitoring Board (DSMB) will determine if the safety data continue to support treatment for an additional 36 or 48 weeks.
At the completion of the EP End of Treatment, subjects will be allowed to enrol in the Alström Rollover Study PBI-4050-CT-9-10 and continue ongoing study medication without any break in treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammation and Fibrosis, Diabetes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PBI-4050
Arm Type
Experimental
Arm Description
Four 200 mg capsules (total 800 mg) administered orally, once daily.
Intervention Type
Drug
Intervention Name(s)
PBI-4050
Intervention Description
Four 200 mg capsules (800 mg total) administered orally, once daily.
Primary Outcome Measure Information:
Title
Description and number of abnormal laboratory values and adverse events that are related to treatment.
Time Frame
Primary on 24 weeks; Final on all data (including Extension Period)
Secondary Outcome Measure Information:
Title
Change from baseline in metabolic syndrome parameters over time.
Description
Change from baseline in fasting plasma glucose over time. Change from baseline in fasting plasma insulin over time. Change from baseline in glycated hemoglobin (HbA1c) over time. Change from baseline in Homeostasis Model Assessment for steady state beta cell function (HOMA-B) and insulin sensitivity (HOMA-S) over time.
Time Frame
24 weeks and end of Extension Period
Title
Change from baseline in biomarkers in blood and urine over time
Description
Percentage of reduction and/or increase of level of biomarkers
Time Frame
24 weeks and end of Extension Phase
Title
Change from baseline in cardiac function parameter: NT-proBNP
Time Frame
24 weeks and end of Extension Phase
Title
Change from baseline of antidiabetic treatment
Description
Dosing change, new medication added or treatment discontinuation
Time Frame
24 weeks and end of Extension Phase
Other Pre-specified Outcome Measures:
Title
Changes from baseline in histological appearances in fat biopsies
Description
Measuring the degree of fibrosis
Time Frame
24 weeks and end of Extension Phase
Title
Changes from baseline in global metabolome and microdialysate fractions
Time Frame
24 weeks and end of Extension Phase
Title
Change from baseline in the liver stiffness
Description
Measured in kilopascal (kPa) correlated to fibrosis by using a FibroScan
Time Frame
24 weeks and end of Extension Phase
Title
Change from baseline in fat content and fibrosis burden in liver MRI
Time Frame
24 weeks and end of Extension Phase
Title
Change from baseline in left ventricular ejection fraction in cardiac MRI
Time Frame
24 weeks and end of Extension Phase
Title
Change from baseline in blood glucose as measured by weekly 4 point profile
Time Frame
24 weeks and end of Extension Phase
Title
Change from baseline in hyperinsulinaemic-euglycaemic clamp measurements.
Time Frame
24 weeks and end of Extension Phase
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria :
Subject is 16 years of age or older at screening.
Subject has signed informed consent.
Subject has a documented diagnosis of Alström syndrome
Subject on diabetes treatment has been receiving the same antidiabetic agent(s) for a minimum of 1 month before screening.
Subject is able and willing to self-monitor blood glucose level at home or can obtain adequate assistance from care givers.
Female subjects of childbearing potential must have a negative serum pregnancy test at screening and agree to use adequate birth control from screening throughout the study and for 30 days after the last Investigational Medicinal Product (IMP) administration. If a male subject 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 30 days after the last IMP administration.
Exclusion Criteria:
Subject has recent or on-going infection requiring systemic treatment with an anti-infective agent within 30 days before screening.
Subject has had at least two documented episodes of severe hypoglycaemia within 12 months before screening
Subject has uncontrolled hypertension with BP > 170/100 mmHg as determined at screening.
Subject has alanine transaminase (ALT) or aspartate transaminase (AST) level ≥ 5 × upper limit of normal (ULN) at screening.
Subject is currently using weight loss medications at screening. Subjects may be re-screened after stopping the weight loss medication for a period of at least 5 half-lives.
Subject has used any moderate/potent inducer or inhibitor of CYP2C9 isozyme or strong inducer or inhibitor of cytochrome P450 (CYP) 3A isozyme within 30 days prior to the first study drug administration.
Subject has a history of chronic alcohol or other substance abuse as determined at screening.
Woman who is pregnant, breast-feeding, or planning a pregnancy during the course of the study as determined at screening.
Subject has any condition that, in the investigator's opinion, is likely to interfere with study conduct and compliance
Subject has a history of an allergic reaction to PBI-4050 or any of its excipients.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tarekegn Hiwot, MD
Organizational Affiliation
The Queen Elizabeth Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals Birmingham NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B15 2PR
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30477455
Citation
Baig S, Veeranna V, Bolton S, Edwards N, Tomlinson JW, Manolopoulos K, Moran J, Steeds RP, Geberhiwot T. Treatment with PBI-4050 in patients with Alstrom syndrome: study protocol for a phase 2, single-Centre, single-arm, open-label trial. BMC Endocr Disord. 2018 Nov 26;18(1):88. doi: 10.1186/s12902-018-0315-6.
Results Reference
derived
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Safety and Tolerability of PBI-4050 and Its Effects on the Biomarkers in Subjects With Alström Syndrome
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