AstraZeneca today announced high-level results from KODIAC-08, an open-label, randomised, 52-week, long-term safety trial of naloxegol versus usual care (UC) in patients with non-cancer related pain and opioid-induced constipation (OIC). UC was defined as the investigator's choice of an existing laxative treatment regimen for OIC. This is the fourth trial in the naloxegol Phase III development programme, and was designed to evaluate the long-term safety and adverse event (AE) profile of naloxegol in patients taking 25 mg once daily, as compared to UC.
In the trial, a total of 534 patients received naloxegol once daily for up to 52 weeks, while 270 patients received UC for OIC during the same treatment period. The most commonly reported AEs occurring more frequently on naloxegol than on usual care included abdominal pain, diarrhoea, nausea and headache. The trial reported no imbalances in serious adverse events (SAEs). In addition, there were a low number of major adverse cardiovascular events (MACE), as adjudicated by an independent external committee, and there was no imbalance of these events across naloxegol and UC arms.
There were no increases from baseline levels in mean daily pain scores or mean total daily opioid dose in either the naloxegol or the UC arm. Additionally, there were no reports of opioid withdrawal AEs which could be attributed to naloxegol. A full assessment of the safety and tolerability findings is ongoing.
"These high-level results are similar to the safety results seen in the Phase III studies previously reported and provide further confidence in the data we've seen to date for naloxegol," said Briggs Morrison , M.D., Executive Vice President, Global Medicines Development, AstraZeneca. "We have now completed our core Phase III programme and we are pleased to advance naloxegol toward a regulatory submission later this year." A New Drug Application (NDA) filing in the US and a Marketing Authorisation Application (MAA) filing in the EU are planned for the third quarter of 2013, pending AstraZeneca's final preparation of the registration package and a pre-NDA meeting with the FDA.
The core Phase III KODIAC programme for naloxegol is comprised of four clinical trials, designed to investigate the safety and efficacy of naloxegol for the treatment of OIC in patients with non-cancer related pain. Three trials reported high level results in November 2012, including KODIAC-04, -05 and -07. KODIAC-04 and -05 were pivotal 12-week efficacy and safety trials, while KODIAC-07 was a 12-week safety extension of KODIAC-04.
Full results from KODIAC-04 and -05 will be presented at Digestive Disease Week (DDW), 18-21 May, 2013. Full results from KODIAC-07, along with KODIAC-08, will be presented at a scientific meeting later in 2013.