Single- and Multiple-Dose Study To Determine the Safety, Tolerability, Pharmacokinetics, and Food Effect of Oral MRX-I versus Linezolid in Healthy Adult Subjects.
A multipart phase 1 study was conducted to determine the safety, tolerability, pharmacokinetics, and food effect of the novel oral oxazolidinone, MRX-I, in healthy adults, as well as the tolerability of longer-term exposure of both oral MRX-I and linezolid. Thirty subjects in part 1 received single ascending doses of MRX-I or placebo under fasting or fed condition in a double-blind crossover design. Twelve subjects in part 2 received MRX-I at 800 mg every 12 h (q12h) for 14 days in a double-blind, placebo-controlled design. In part 3, 24 subjects were randomized to receive 28 days of MRX-I at 800 mg q12h or oral linezolid at 600 mg q12h for 28 days in a double-blind, double-dummy design. Oral MRX-I was associated with a greater bioavailability and exposure when administered with food, and minimal accumulation of MRX-I occurred after multiple-dose administration. Oral MRX-I was well tolerated at single doses of up to 1,200 and 800 mg q12h for up to 28 days; all adverse events were mild to moderate in severity, and there was no drug discontinuation due to adverse events. These data support further clinical development of oral MRX-I in the treatment of resistant Gram-positive bacterial infections.
MicuRx Pharmaceuticals, Inc., Hayward, California, USA peckburg@gmail.com.
Paul B
0000-0001-6133-9057
PB
Eckburg
MicuRx Pharmaceuticals, Inc., Hayward, California, USA.
Yigong
Y
Ge
MicuRx Pharmaceuticals, Inc., Hayward, California, USA.
Barry
B
Hafkin
D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D015992:Body Mass Index; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D064368:Healthy Volunteers; D006801:Humans; D000069349:Linezolid / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D015233:Models, Statistical; D023303:Oxazolidinones / Q000097:blood / Q000493:pharmacokinetics*; D061214:Patient Safety; D011728:Pyridones / Q000097:blood / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D011728:Pyridones; C000590780:contezolid; D000069349:Linezolid
MRX-I; linezolid; oxazolidinones; phase 1