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Safety and Tolerability of PBI-4050 and Its Effects on the Biomarkers in Subjects With Alström Syndrome

Phase 2
Completed
Conditions
Inflammation and Fibrosis
Diabetes
Interventions
Registration Number
NCT02739217
Lead Sponsor
Liminal BioSciences Ltd.
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12
Inclusion Criteria

Not provided

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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
PBI-4050PBI-4050Four 200 mg capsules (total 800 mg) administered orally, once daily.
Primary Outcome Measures
NameTimeMethod
Description and number of abnormal laboratory values and adverse events that are related to treatment.Primary on 24 weeks; Final on all data (including Extension Period)
Secondary Outcome Measures
NameTimeMethod
Change from baseline in cardiac function parameter: NT-proBNP24 weeks and end of Extension Phase
Change from baseline in metabolic syndrome parameters over time.24 weeks and end of Extension Period

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 time24 weeks and end of Extension Phase

Percentage of reduction and/or increase of level of biomarkers

Change from baseline of antidiabetic treatment24 weeks and end of Extension Phase

Dosing change, new medication added or treatment discontinuation

Trial Locations

Locations (1)

University Hospitals Birmingham NHS Foundation Trust

🇬🇧

Birmingham, United Kingdom

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