Phase 2 Data From Oral NKTR-118 Presented at American College of Gastroenterology in San Diego
New Approach to Treat Opioid-Induced Constipation
SAN DIEGO, Oct. 27 /PRNewswire-FirstCall/ -- Data from a phase
II study demonstrated that oral NKTR-118 improved lower
gastrointestinal dysfunction by increasing the frequency of bowel
movements in patients with opioid-induced constipation, while
simultaneously preserving opioid-mediated analgesia. NKTR-118, an
oral peripherally-acting opioid antagonist, is an investigational
product candidate in clinical development for the treatment of
In the phase II double blind, randomized, placebo-controlled
study of 208 patients with opioid-induced constipation, NKTR-118
achieved the primary endpoint of change from baseline in
spontaneous bowel movements (SBMs). Patients receiving either 25 mg
or 50 mg of oral NKTR-118 once daily had a significantly greater
change from baseline in SBMs during the first week of treatment
than patients receiving placebo. The mean change from baseline in
SBMs per week for patients receiving 25 mg NKTR-118 was 3.6 versus
1.9 in the placebo group (p= 0.002). Patients receiving 50 mg
NKTR-118 had a mean change from baseline in SBMs per week of 4.4
versus 1.9 in the placebo group (p=0.0001). The increase from
baseline in SBMs versus placebo averaged over the four-week
treatment period was significant for both the 25 mg (p=0.002) and
50 mg (p<0.0001) dose groups. Results for the 5 mg dose of
NKTR-118 were not significant.
The study also showed that there was a statistically significant
difference in median time to first SBM for patients in the 25 mg
and 50 mg dose cohorts as compared to placebo. Median time to first
SBM for patients in the 25 mg dose cohort was 6.6 hours as compared
to placebo which was 48.6 hours (p=0.001), and for patients in the
50 mg dose cohort, median time to first SBM was 2.9 hours as
compared to placebo, which was 44.9 hours (p<0.002). Results for
the 5 mg dose of NKTR-118 were not significant.
"Patients who take opioids are at risk of experiencing the
painful and potentially serious side effect of opioid-induced
constipation (OIC) -- which can require patients to seek remedies
only available in a hospital or in-office setting," said Dr. Lynn
Webster, Medical Director of Lifetree Clinical Research and lead
clinical investigator of the phase II trial. "The results of the
NKTR-118 phase II trial presented today indicate that, if approved,
this product may have the potential to offer patients suffering
from OIC a simple and non-invasive oral treatment that may improve
their gastrointestinal function."
The study also showed there was no apparent reversal of
opioid-mediated analgesia with any of the NKTR-118 dose groups, as
measured by no change in Numeric Rating Scale (NRS) pain scores and
no increase in mean daily opiate use.
The most commonly reported side effects from this Phase II study
of NKTR-118 were dose dependent gastrointestinal-related effects.
The majority of side effects for both the 5 and 25 mg dose cohorts
were graded as mild by the investigators. Side effects included
diarrhea (13% at 25 mg and 31% at 50 mg, versus 4% and 5% for the
placebo arms), nausea (13% for 25 mg and 20% for 50 mg, versus 19%
and 8% for the placebo arms) and abdominal pain (30% for 25 mg and
17% for 50 mg, versus 7% and 0% for the placebo arm). No
treatment-related serious adverse events (SAE) for the 5 or 25 mg
cohorts were observed. Only one patient experienced an SAE of
hospitalization due to abdominal cramping in the 50 mg
These data from the Phase II clinical trial of NKTR-118 were
presented today during the oral plenary session of the American
College of Gastroenterology (ACG) 2009 Annual Clinical
On September 21, 2009, AstraZeneca and Nektar Therapeutics
announced that they entered into an exclusive worldwide license
agreement for NKTR-118 and NKTR-119.
NKTR-118 is an investigational drug candidate that combines
Nektar's advanced small molecule polymer conjugate technology
platform with naloxol, a derivative of the opioid-antagonist drug,
Top line results of the phase II study were presented at the
American Academy of Pain Management in early October, 2009.
About Opioid-Induced Constipation
It is estimated that for those patients who take opiates
chronically for pain management, anywhere from 40-90% of such
patients will develop constipation. Less than half of those
patients find effective relief from current treatment options that
include prescription and over-the-counter laxatives and stool
softeners. These symptoms of bowel dysfunction are a result of the
drug binding to the mu-opioid receptor in the gut (1).
Opioid-induced bowel dysfunction encompasses symptoms such as
constipation, bloating, abdominal cramping, and gastroesophageal
reflux. Constipation is the hallmark of this syndrome and is
generally its most prominent component.
According to IMS Health, about 230 million prescriptions were
written for opioids in 2007 in the United States alone. This is
estimated to represent about 65-75% of the worldwide opioid market.
Currently, there are no oral drugs approved that are indicated to
treat opioid-induced constipation. Opioid bowel dysfunction and
opioid-induced constipation can significantly impact quality of
life and increase healthcare utilization.
AstraZeneca is a major international healthcare business engaged
in the research, development, manufacturing and marketing of
meaningful prescription medicines and supplier for healthcare
services. AstraZeneca is one of the world's leading pharmaceutical
companies with healthcare sales of US$ 31.6 billion and is a leader
in gastrointestinal, cardiovascular, neuroscience, respiratory,
oncology and infectious disease medicines. For more information
about AstraZeneca, please visit: www.astrazeneca.com.
Nektar Therapeutics (NASDAQ:NKTR) is a biopharmaceutical company
developing novel therapeutics based on its PEGylation and advanced
polymer conjugation technology platforms. Nektar's technology and
drug development expertise have enabled nine approved products in
the U.S. or Europe for partners, which include leading
biopharmaceutical companies, including UCB's Cimzia®, Roche's
PEGASYS® for hepatitis C and Amgen's Neulasta® for
neutropenia. Nektar has created a robust pipeline of potentially
high-value therapeutics to address unmet medical needs by
leveraging and expanding its technology platforms to improve and
enable molecules. Nektar is currently conducting clinical and
preclinical programs in oncology, pain and other therapeutic areas.
NKTR-102, PEGylated irinotecan, is currently in Phase 2 clinical
studies in ovarian, breast and colorectal cancer. NKTR-105,
PEGylated docetaxel, is currently in a Phase 1 clinical study in
patients with refractory solid tumors.
Nektar is headquartered in San Carlos, California, with
additional R&D operations in Huntsville, Alabama and Hyderabad,
India. Further information about the company and its drug
development programs and capabilities may be found online at
1. Panchal SJ, Muller-Schwefe P, Wurzelmann JI. Opioid-induced
bowel dysfunction: prevalence, pathophysiology and burden. Int J
Clin Pract. 2007;61(7):1181-1187.
CONTACT: US PR inquiries: Emily Denney, +1-302-885-3451, Global
inquiries: Michele Meeker, +1-302-885-6351, both of AstraZeneca; or Nektar PR
& IR Inquiries: Jennifer Ruddock, +1-650-631-4954
Web Site: http://www.astrazeneca.com/
Posted: October 2009