AstraZeneca announced enrollment of the first patient in the phase III clinical programme for NKTR-118, an oral peripherally-acting opioid antagonist being investigated for the treatment of Opioid-Induced Constipation (OIC). The phase III clinical programme is designed to investigate the safety and efficacy of NKTR-118 as a medicine to relieve opioid induced constipation, a common side effect of prescription opioids when used for chronic pain management. NKTR-118 is part of the exclusive worldwide license agreement announced on 21 September 2009, between AstraZeneca and Nektar Therapeutics.
The phase III clinical programme will consist of two 12-week, randomized, placebo-controlled efficacy studies (with approximately 630 randomized patients each) and an open-label, randomized, long-term safety study with a “usual care” comparator arm. The 12-week efficacy studies will compare response rate among placebo and two different doses of NKTR-118 with primary endpoint at 4 weeks. There is a three month safety extension following one of the two 12-week studies.
The long-term safety study will include patients from the 12-week treatment in the efficacy studies, as well as new patients not previously enrolled. All patients will be randomly assigned to open-label treatment of either NKTR-118 or physician’s choice (usual care) of laxative regimen. Safety assessments will also be collected throughout the trials.
“This is a key milestone for NKTR-118,” said Anders Ekblom, executive vice president of Global Medicines Development, AstraZeneca. “We will put our knowledge and our effort into studying NKTR-118 as a potential effective new treatment option for Opioid-Induced Constipation, which continues to be an area of unmet need in patients needing effective pain treatment.”
NKTR-118 is an investigational drug candidate being developed as a once-daily oral tablet for the treatment of Opioid-Induced Constipation. It combines Nektar's advanced small molecule polymer conjugate technology platform with naloxol, a derivative of the opioid antagonist drug, naloxone. Top line results of the phase II study of NKTR-118 were presented in October 2009 at the American College of Gastroenterology Annual Clinical Meeting and the American Academy of Pain Management. In addition, the company is also developing NKTR-119, a co-formulation of oral NKTR-118 and an opioid analgesic.
Clinically, OIC is the most prevalent side effect of opioid therapy. For those patients who take opiates for long term pain management, approximately 40-50 percent will develop constipation. Only about 40-50 percent of those patients experience effective relief from the treatment options that include prescription and over-the-counter laxatives and stool softeners.
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease.
Nektar Therapeutics is a clinical-stage biopharmaceutical company developing novel therapeutics based on its PEGylation and advanced polymer conjugate technology platforms.