A203 ACTIVITY OF MBX-8025, A POTENT AND SELECTIVE PPAR-δ AGONIST, ON BIOCHEMICAL MARKERS OF CHOLESTASIS
| Autor: | C A McWherter, Y Choi, P F Boudes, Alexandra Steinberg |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
chemistry.chemical_classification
Agonist medicine.medical_specialty Bilirubin medicine.drug_class Atorvastatin MBX-8025 Peroxisome proliferator-activated receptor medicine.disease Poster Presentations chemistry.chemical_compound Endocrinology Cholestasis chemistry Internal medicine medicine Alkaline phosphatase Peroxisome proliferator-activated receptor delta medicine.drug |
| Zdroj: | Journal of the Canadian Association of Gastroenterology. 1:355-356 |
| ISSN: | 2515-2092 2515-2084 |
| DOI: | 10.1093/jcag/gwy008.204 |
| Popis: | BACKGROUND: MBX-8025 is a potent and selective PPAR-delta agonist that decreases LDL-Cholesterol in subjects with mixed dyslipidemia and subjects with homozygous familial hypercholesterolemia (HoFH). AIMS: Herein, we describe the activity of MBX-8025 to decrease biochemical markers of cholestasis. METHODS: Alkaline phosphatases (AP), gamma glutamyl transferase (GGT), and total bilirubin (TB) were measured in three clinical studies: a 3-week parallel groups, placebo-controlled study in healthy volunteers; an 8-week parallel groups, placebo- and atorvastatin-controlled study in mixed dyslipidemia; and a 12-week dose escalating, non-controlled study in HoFH. MBX-8025 was administered orally, daily, at doses of 50, 100 and 200 mg. None of the subjects had a medical diagnosis of cholestasis and AP levels were considered within the normal range. RESULTS: Rapid onset (within 4 days) and consistent decreases in AP were observed in all three studies. Decreases were sustained during MBX-8025 treatment, reversible within a week upon discontinuation of MBX-8025, and AP values were not seen below the lower reference limit. The AP decrease was not consistently dose-dependent and was associated with a concomitant decrease in GGT of similar amplitude. Decreases (between -20% and -40%) in TB were also observed in healthy volunteers and patients with HoFH. CONCLUSIONS: MBX-8025 significantly decreases biochemical markers of cholestasis in three different populations. A recent study in primary biliary cholangitis (NCT02609048) confirmed that this activity was translated in patients with cholestasis and was associated with a decrease in bile acid synthesis. FUNDING AGENCIES: CymaBay Therapeutics |
| Databáze: | OpenAIRE |
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