Alström Syndrome MedDRA version: 19.1 Level: LLT Classification code 10068814 Term: Alstrom syndrome System Organ Class: 100000004850
Conditions
Interventions
Product Code: PBI-4050
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: 3-pentylbenzeneacetic acid sodium salt
CAS Number: 1254472-97-3
Sponsors
ProMetic BioSciences Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject is 16 years of age or older at screening. 2. Subject has signed informed consent. 3. Subject has a documented diagnosis of Alström syndrome, confirmed by genetic testing before screening. 4. Subject on diabetes treatment has been receiving the same antidiabetic agent(s) for a minimum of 1 month before screening. 5. Subject is able and willing to self-monitor blood glucose level at home or can obtain adequate assistance from care givers. 6. Female subjects of childbearing potential who are sexually active with a nonsterile male partner must have a negative serum or urine pregnancy test at screening and agree to use adequate birth control from screening throughout the study and for 30 days after the last 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. Explanatory note: A female subject is considered to be of childbearing potential unless she has had a hysterectomy, is at least one year post-menopausal, or has undergone tubal ligation. Adequate birth control includes at least one medically approved and highly effective method of birth control, defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, oral contraceptives combined with at least one barrier method. Acceptable contraceptive methods for a male subject include simultaneous use of condoms and, for his female partner, the use of hormonal contraceptives, intra-uterine contraceptive device, or diaphragm with intravaginally applied spermicide. Only male subjects whose vasectomy has been confirmed by semen analysis at least 3 months after the vasectomy are allowed not to use acceptable contraceptive methods. Are the trial subjects under 18? yes Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 17 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Subject has recent or on-going infection requiring systemic treatment with an anti-infective agent within 30 days before screening. 2. Subject has had at least two documented episodes of severe hypoglycaemia within 12 months before screening. Severe hypoglycaemia is defined as an episode of confirmed hypoglycaemia (glucose 170/100 mmHg as determined at screening. 4. Subject has alanine transaminase (ALT) or aspartate transaminase (AST) level = 5 × upper limit of normal (ULN) at screening. 5. 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. 6. Subject has used any moderate/potent inducer or inhibitor of CYP2C9 isozyme or any strong inducer or inhibitor of cytochrome P450 (CYP) 3A isozyme within 30 days prior to the first study drug administration. 7. Subject has a history of chronic alcohol or other substance abuse as determined at screening. 8. Woman who is pregnant, breast-feeding, or planning a pregnancy during the course of the study as determined at screening. 9. Subject has any condition that, in the investigator’s opinion, is likely to interfere with study conduct and compliance. 10. Subject has a history of an allergic reaction to PBI-4050 or any of its excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the safety and tolerability of 800mg PBI-4050 (the Investigational Medicinal Product), administered orally once daily for 24 weeks, in subjects with Alström Syndrome.;Timepoint(s) of evaluation of this end point: Assessments during study visits at weeks 4, 8, 12, 16, 20, 24, EP12, EP24, EP36, EP48, and 30 days after final dose.; Secondary Objective: The secondary objectives are: - To evaluate the effect of the IMP (PBI-4050) on metabolic syndrome parameters - To evaluate the effect of the IMP on pro-inflammatory/inflammatory, fibrotic, diabetic, and obesity biomarkers in blood and urine - To evaluate the effect of the IMP on anti diabetic treatment, including oral therapy and insulin requirements. The exploratory objectives are: - To examine the effect of the IMP on the histological appearances seen in fat biopsies, in particular the degree of fibrosis and macrophage infiltration. - To analyse the effect of the IMP on global metabolome (smallmolecule chemicals found within a biological sample) using the systemic blood samples and adipose tissue-specific micro dialysis samples. - To analyse the effect of the IMP on the microdialysate fractions using the adipose tissue micro dialysis samples. - To assess the effect of the IMP on liver stiffness using the FibroScan - To measure the effect of the IMP on the fat content ; Primary end point(s): Safety: • AEs • AEs of special interest: incidence of hypoglycaemia (despite adequate adjustment of other antidiabetic concomitant medication): o Suspected symptomatic hypoglycaemia: Symptoms of hypoglycaemia | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: • Changes from baseline in metabolic syndrome parameters: o Fasting plasma glucose o Haemoglobin A1c (HbA1c) o Fasting insulin o Homeostasis Model Assessment for steady state beta cell function (HOMA-B) and insulin sensitivity (HOMA-S) • Changes from baseline in pro-inflammatory/ inflammatory, fibrotic, diabetic, and obesity markers: o Blood: interferon gamma (IFN?), cystatin C, interleukin 6 (IL-6), IL-8, monocyte chemoattractant protein 1 (MCP-1), tumour necrosis factor alpha (TNFa), IL-10, high-specificity C-reactive protein (hsCRP), vascular endothelial growth factor (VEGF), adiponectin, glucagon o Urine: albumin/creatinine ratio (ACR, in mg/mmol), MCP-1 • Change from baseline in cardiac function parameter: NT proBNP • Changes from baseline in antidiabetic medications, including oral and insulin therapies and dosages. ;Timepoint(s) of evaluation of this end point: Assessments during study visits at weeks 4, 8, 12, 16, 20, 24, EP12, EP24, EP36, EP48, and 30 days after final dose. | — |
Countries
United Kingdom
Contacts
Public ContactTanya Palmer
ProMetic Biosciences Inc.
Outcome results
None listed