SAN CARLOS, Calif., Jan. 8 /PRNewswire-FirstCall/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced the start of its Phase 2 study for NKTR-118 (PEG-naloxol), an oral treatment being developed to treat opioid-induced constipation (OIC) and other clinical manifestations of opioid-induced bowel dysfunction (OBD). The double-blind, randomized, dose-escalation trial will evaluate the efficacy, safety and tolerability of NKTR-118 in patients experiencing constipation while receiving opioid therapy.
"We are excited to begin our Phase 2 clinical trial for oral NKTR-118 in OBD and OIC patient settings," said Hoyoung Huh, M.D., Ph.D. Chief Operating Officer and Head of the PEGylation Business Unit at Nektar. "NKTR-118 represents an innovative application of our small molecule PEGylation technology to prevent drugs from entering the central nervous system."
NKTR-118 is being evaluated as an oral therapy to treat OBD and OIC, which are serious and debilitating conditions resulting from the use of opioids for pain management. NKTR-118, which is a PEGylated form of naloxol, was designed to selectively target peripheral opioid receptors to alleviate constipation associated with opioid therapy, while reducing the drug's penetration across the blood-brain barrier (BBB) and into the central nervous system in order to preserve opioid analgesia.
About the Phase 2 Clinical Development Program for NKTR-118 (oral PEG-naloxol)
The Phase 2 trial for NKTR-118 is a multi-center, placebo-controlled, dose-escalation trial (5 mg, 25 mg, 50 mg or 100 mg). Patients experiencing OIC will be randomized 1:1 to NKTR-118 or placebo in addition to their opioid treatment. Therapy will be administered orally once-daily (QD) over a five-week treatment period. The primary efficacy endpoint of the trial will be the increase from baseline in spontaneous bowel movements per week (SBMs per week). Additional endpoints include monitoring of other symptoms of OBD, which will include the Patient Assessment of Constipation Symptoms (PAC-SYM) outcomes tool, and other quality of life measures. Maintenance of opioid analgesic effect will be assessed by measuring changes from baseline in mean daily opioid requirements and daily pain scores. Safety and tolerability will be assessed and pharmacokinetics of the drug will be evaluated. The trial will be conducted in approximately 50 centers in North America and Europe.
NKTR-118 is an oral drug that combines Nektar's advanced small molecule PEGylation technology platform with naloxol, a derivative of the opioid-antagonist drug, naloxone. In preclinical studies, Nektar's PEGylation technology has been shown to reduce penetration of drugs across the blood-brain barrier, an important potential advance for NKTR-118 and possibly many other small molecule therapies.
The peripheral opioid antagonist NKTR-118 targets opioid receptors within the enteric nervous system, which mediate OBD, a symptom complex resulting from opioid use that encompasses constipation, bloating, abdominal cramping, and gastroesophageal reflux. Constipation is the hallmark of this syndrome, and is generally its most prominent component. Currently, there are no specific drugs approved or specifically indicated to treat OBD or OIC. NKTR-118 has been studied in two Phase 1 trials evaluating the safety, tolerability and pharmacokinetics of single and repeated dose administration of the drug.
In a proof-of-principle Phase 1 trial, single oral doses of NKTR-118 antagonized morphine-induced delay in gastrointestinal transit time demonstrating the potential of the drug to relieve constipation caused by opioid treatment. This effect was seen to increase in a dose-dependent fashion, reaching maximal effect at 125 mg. Further, no diminution of morphine-induced miosis, a CNS effect, was observed at single oral doses of NKTR-118 that produced a maximal effect on gastrointestinal transit time. NKTR-118 was well-tolerated and rapidly absorbed with dose proportional pharmacokinetics over single dose ranges of 8-1,000 mg.
According to IMS Health, more than 200 million prescriptions were written for opioids in 2006 in the United States, alone. Many studies indicate that a high percentage of patients receiving opioids are likely to experience significant constipation and other symptoms of OBD. Stool softeners or laxatives may be inadequate for many patients with OIC and often are associated with unwanted side effects such as bloating and cramping.
Data Presentations for NKTR-118
Study results from Phase 1 and preclinical trials for NKTR-118 were presented at the American College of Clinical Pharmacology conference and the American Academy of Pain Management's Annual Clinical Meeting in September 2007. These presentations can be found at: http://www.nektar.com/wt/page/nktr118_media
Nektar Therapeutics is a biopharmaceutical company that develops and enables differentiated therapeutics with its industry-leading PEGylation and pulmonary drug development platforms. Nektar PEGylation and pulmonary technology, expertise, and manufacturing capabilities have enabled ten approved products for partners, which include the world's leading pharmaceutical and biotechnology companies. Nektar also develops its own products by applying its PEGylation and pulmonary technology platforms to existing medicines with the objective to enhance performance, such as improving efficacy, safety and compliance.
This press release contains forward-looking statements that reflect the
company's current views as to the value, relative competitive position, and
application of the company's technology platforms, and statements regarding
the progress, potential, and future clinical plans for NKTR-118. These
forward-looking statements involve risks and uncertainties, including but
not limited to: (i) the company's proprietary product candidates, including
NKTR- 118, are in the early phases of clinical development and the risk of
failure is high and can unexpectedly occur at any stage, (ii) the timing or
success of the commencement or conclusion of planned clinical trials is
subject to a number of uncertainties including but not limited to clinical
design, patient enrollment, regulatory requirements and clinical outcomes,
(iii) the company's success in meeting minimum clinical end points and
obtaining regulatory approvals for product candidates, such as NKTR-118
(iv) the company's patent applications for its proprietary product
candidates may not issue, patents that have issued may not be enforceable
or sufficient to protect against competitive products, or intellectual
property licenses from third parties may be required in the future, (v) the
outcome of any future intellectual property or other litigation related to
the company's proprietary product candidates, such as NKTR-118 and (vi)
potential competition from existing approved products (branded, generic or
over-the-counter) or product candidates under development by other
companies could negatively impact the commercial potential of the company's
product candidates due to such competitive factors as efficacy and safety
profiles, pricing, and reimbursement by third party payers. Other important
risks and uncertainties are detailed in the company's reports and other
filings with the Securities and Exchange Commission (SEC), including its
most recent Quarterly Report on Form 10-Q filed with the SEC on November 9,
2007. Actual results could differ materially from the forward- looking
statements contained in this press release. The company undertakes no
obligation to update forward-looking statements, whether as a result of new
information, future events or otherwise.
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|SOURCE Nektar Therapeutics|
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