Abstract | BACKGROUND: METHODS: Six FCS patients were enrolled in an open-label clinical study. Following a 1-week very low fat diet run-in period patients underwent baseline lipid assessments, including a low fat meal tolerance test. Patients then underwent three consecutive 21 day treatment periods ( pradigastat at 20, 40 & 10 mg, respectively). Treatment periods were separated by washout periods of ≥4 weeks. Fasting TG levels were assessed weekly through the treatment periods. Postprandial TGs, ApoB48 and lipoprotein lipid content were also monitored. RESULTS: Following once daily oral dosing, steady-state exposure was reached by Day 14. There was an approximately dose proportional increase in pradigastat exposure at studied doses. Pradigastat was associated with a 41% (20 mg) and 70% (40 mg) reduction in fasting triglyceride over 21 days of treatment. The reduction in fasting TG was almost entirely accounted for by a reduction in chylomicron TG. Pradigastat treatment also led to substantial reductions in postprandial TG as well as apo48 (both fasting and postprandial). Pradigastat was safe and well tolerated, with only mild, transient gastrointestinal adverse events. CONCLUSION: The novel DGAT1 inhibitor pradigastat substantially reduces plasma TG levels in FCS patients, and may be a promising new treatment for this orphan disease. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01146522 .
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Authors | Charles Daniel Meyers, Karine Tremblay, Ahmed Amer, Jin Chen, Liewen Jiang, Daniel Gaudet |
Journal | Lipids in health and disease
(Lipids Health Dis)
Vol. 14
Pg. 8
(Feb 18 2015)
ISSN: 1476-511X [Electronic] England |
PMID | 25889044
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Acetates
- Aminopyridines
- Apolipoprotein B-48
- Triglycerides
- pradigastat
- DGAT1 protein, human
- Diacylglycerol O-Acyltransferase
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Topics |
- Acetates
(therapeutic use)
- Adult
- Aged
- Aminopyridines
(therapeutic use)
- Apolipoprotein B-48
(blood)
- Diacylglycerol O-Acyltransferase
(antagonists & inhibitors)
- Female
- Humans
- Hyperlipoproteinemia Type I
(blood, drug therapy)
- Male
- Middle Aged
- Triglycerides
(blood)
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