Phase 1 Studies with Severe Triglyceridemia Drug, CAT-2003, Very Impressive

RDR Staff

Donovan et al presented their poster “Phase I Single and Multiple Ascending Dose Study of CAT-2003, a Novel Activator of Lipoprotein Lipase, Demonstrates Reductions in Postprandial Triglycerides” at the 2014 National Lipid Association (NLA) Scientific Sessions in Orlando, FL. The presentation summarized the phase I studies recently completed that allow Catabasis Pharmaceuticals, the makers of CAT-2003, to begin more clinical trials in patients with severe hypertriglyceridemia and chylomicronemia.

CAT-2003 modulates the sterol-regulatory element-binding protein (SREBP) pathway to increase lipoprotein lipase (LPL) activity and reduces triglycerides. Catabasis Pharmaceuticals is developing CAT-2003 as an oral, small molecule designed to treat severe hypertriglyceridemias, including rare chylomicronemia syndromes. 

Clinical Data

Two phase I studies were conducted in normal healthy volunteers (screened for flushing with 500-mg immediate-release niacin).

In the first study, subjects were given single ascending doses of CAT-2003 from 300 mg to 2000 mg, either after fasting or immediately after a high-fat breakfast (450 kcal as fat). Outcomes measured were flushing measurements for 4 hours in the fasting subjects and postprandial measurements in the high-fat-breakfast-eating subjects. 

Subjects in the second study were given ascending dosages of CAT-2003 (500 mg QD/500 mg BID/1000 mg QD/1000 mg BID) for 14 days (after fasting or a high-fat breakfast). Outcome measures were flushing measured after dosing on day 1 and day 14 in fasting subjects, and postprandial measurements in the high-fat-breakfast subjects on day 1 and 14.

In the single-dose study, CAT-2003 at dosages of 1000 mg (n=7), and 2000 mg (n=4) were found to significantly lower postprandial plasma triglycerides compared with placebo (n=6). Flushing was not reported in the subjects. In the multidose study, all dosages were found to suppress postprandial increases in triglyceride level after 14 days of dosing. Interestingly, in subjects with fasting triglycerides >150 mg/dL, their fasting triglyceride levels dropped by approximately 30% following CAT-2003 (at all dosages). 

Regarding adverse events, the poster noted that 82 volunteers were given CAT-2003, and there have been no reports of any abnormalities in laboratory values, vital signs, ECG, or physical examination. Mild diarrhea, nausea, headache, and vomiting were reported in some volunteers.

In conclusion, the phase I studies with CAT-2003 showed the drug to be safe and well tolerated, it did not show niacin-like activity (ie, no flushing), and it lowered elevated levels of triglycerides in a dose-dependent manner.

CT-2003 is currently in phase II studies, including one in patients with chylomicronemia.


Donovan JM, Dunbar R, Biernat L, et al. Phase I single and multiple ascending dose study of CAT-2003, a novel activator of lipoprotein lipase, demonstrates reductions in postprandial triglycerides. Poster presented at: National Lipid Association Scientific Sessions; May 1-4, 2014; Orlando FL. Poster #119.

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