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

NCT02739217 | Completed Phase 2 DMC

• 1 other identifier: PBI-4050-ATX-9-05
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Inflammation and Fibrosis; Diabetes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change from baseline in metabolic syndrome parameters over time.

  24 weeks and end of Extension Period

• Change from baseline in biomarkers in blood and urine over time

  24 weeks and end of Extension Phase

• Change from baseline in cardiac function parameter: NT-proBNP

  24 weeks and end of Extension Phase

• Change from baseline of antidiabetic treatment

  24 weeks and end of Extension Phase

Other Outcomes (7)

• Changes from baseline in histological appearances in fat biopsies

  24 weeks and end of Extension Phase

• Changes from baseline in global metabolome and microdialysate fractions

  24 weeks and end of Extension Phase

• Change from baseline in the liver stiffness

  24 weeks and end of Extension Phase

Study Arms (1)

PBI-4050

EXPERIMENTAL

Four 200 mg capsules (total 800 mg) administered orally, once daily.

Drug: PBI-4050

Interventions

PBI-4050 DRUG

Four 200 mg capsules (800 mg total) administered orally, once daily.

PBI-4050

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Liminal BioSciences Ltd.: lead

Study Sites (1)

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2PR, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30477455 DERIVED

MeSH Terms

Conditions

Inflammation; Fibrosis; Diabetes Mellitus

Interventions

setogepram

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Tarekegn Hiwot, MD

  The Queen Elizabeth Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2016
• First Posted: April 15, 2016
• Study Start: February 22, 2016
• Primary Completion: September 26, 2017
• Study Completion: June 4, 2018
• Last Updated: August 29, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)