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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

About this trial

This is an interventional treatment trial for Inflammation and Fibrosis

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

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

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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