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ARTICLE | Clinical News

AstraZeneca reports Phase III naloxegol safety data

February 27, 2013 1:44 AM UTC

AstraZeneca plc (LSE:AZN; NYSE:AZN) said once-daily oral naloxegol for up to 52 weeks led to no imbalance in serious adverse events or major adverse cardiovascular events (MACE) -- of which there were an undisclosed but "low number" -- vs. usual care in the Phase III KODIAC-08 trial to treat opioid-induced constipation (OIC). Usual care was defined as the investigator's choice of an existing laxative treatment regimen for OIC. The open-label trial enrolled 804 OIC patients with non-cancer pain.

Last November, partner Nektar Therapeutics (NASDAQ:NKTR) disclosed in a 10-Q filing that "FDA is exploring whether there is any evidence of a potential cardiovascular class effect related to opioid withdrawal associated with mu opioid antagonists." Naloxegol (formerly NKTR-118) is a PEGylated form of naloxol, a peripheral mu opioid receptor ( OPRM1; MOR) antagonist. Nektar said AstraZeneca is conducting "comprehensive safety studies" as part of the KODIAC development program, and that data from the Phase III KODIAC-04, KODIAC-05 and KODIAC-07 extension of KODIAC-04 showed that there were no "clinically relevant" imbalances in serious adverse events, including major CV events, between treatment arms. Also last November, the Phase III KODIAC-04 and KODIAC-05 trials showed that naloxegol met the primary endpoint of a greater proportion of OIC responders at week 12 vs. placebo in each of the trials (see BioCentury Extra, Nov. 12, 2012). ...