Table 1.

Therapeutic efficacy and side effects of CDDO-Me in clinical trials

Indication	Phase	Treatment method	Sample size	Efficacy	Side effects	Reference
Stage 3b–4 CKD and type 2 diabetes	II	25 mg of CDDO-Me daily for 28 days, followed by 75 mg daily for another 28 days	20 patients	The study found an improvement in 90% of patients’ eGFR, with average in estimated glomerular filtration rate of 7.2 mL/min/1.73 m2	No life-threatening adverse events or drug-related serious adverse events	Pergola et al37
CKD	IIb	Placebo or CDDO-Me at a target dose of 25, 75, or 150 mg once daily	227 patients	eGFR improvement of 8.2±1.5 mL in 25 mg group, 11.4±1.5 mL in the 75 mg group, and 10.4±1.5 mL in the 150 mg group and maintained through week 52	Muscle spasms, hypomagnesemia, increases in alanine aminotransferase and gastrointestinal effects	Pergola et al38
Type 2 diabetes mellitus and stage 4 CKD	III	Placebo or CDDO-Me at a daily dose of 20 mg	2,185 patients	In the CDDO-Me group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes	Heart failure	de Zeeuw et al16
Stage II–IV pancreatic adenocarcinoma	I	Various concentrations of CDDO-Me combined with gemcitabine	19 patients	Neutralizes the activity of MDSC and improves antitumor immune responses	No toxicity was observed	Nagaraj et al17
Solid tumors and lymphomas	I	Administered orally once daily for 21 consecutive days of a 28-day cycle for up to 12 cycles from 5 mg/day to 1,300 mg/day	47 patients	The MTD was established as 900 mg/day. A complete tumor response occurred in a mantle cell lymphoma patient	Fatigue, nausea, anorexia and liver transaminase elevations	Hong et al18

Abbreviations: CDDO-Me, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; MDSC, myeloid-derived suppressor cells; MTD, maximum tolerated dose.