MOVANTIKTM (naloxegol) Safety Analyses of Opioid-Induced Constipation Patients 65 and Older with Chronic Non-Cancer Pain
May 16 2015 - 9:30AM
Business Wire
Data Presented at the 2015 Digestive Disease
Week (DDW)
Further analysis of the Phase III KODIAC-04, KODIAC-05 and
KODIAC-08 studies presented today at Digestive Disease Week (DDW)
2015 in Washington, D.C. showed that MOVANTIKTM (naloxegol) had a
similar incidence of adverse events (AEs) among elderly patients as
compared to placebo or usual care. The study evaluated the effects
of daily oral administration of MOVANTIK 12.5 mg or 25 mg vs
placebo among outpatients 65 years and older with opioid-induced
constipation (OIC) and chronic non-cancer pain.
The incidence of AEs reported among patients taking MOVANTIK was
similar to those taking placebo or usual care. Safety results among
this subset were generally consistent with those seen in the
overall patient populations from phase 3 studies.
Specific findings from the sub-analyses of patients aged 65
years and older included:
- In the KODIAC-04 and KODIAC-05
(n=147/1,331) studies:
- The incidence of AEs was: naloxegol
12.5 mg, 50.0% (22/44); naloxegol 25 mg, 56.6% (30/53); placebo,
62.0% (31/50)
- The most common gastrointestinal (GI)
AEs in older patients taking naloxegol were diarrhea, vomiting,
nausea, and abdominal pain
- No GI events were adjudicated as
related to bowel perforation
- The incidence of serious AEs (SAEs:
placebo, 4.0% (2/50); naloxegol 12.5 mg, 6.8% (3/44); naloxegol 25
mg, 3.8% (2/53) and discontinuations due to AEs (placebo, 8.0%
(4/50); naloxegol 12.5 mg, 6.8% (3/44); naloxegol 25 mg, 7.5%
(4/53) were comparable among treatment groups in the 12-week
pool
- One patient (aged 73 years, receiving
naloxegol 12.5 mg) had an adjudicated cardiovascular event (acute
myocardial infarction) that was judged unrelated to treatment
- In the KODIAC-08 (n=76/721) study:
- The incidence of AEs was: naloxegol 25
mg, 86.7% (39/45); usual care, 83.9% (26/31)
- The most common GI AEs in older
patients taking naloxegol were diarrhea, vomiting, nausea, and
abdominal pain
- No GI events were adjudicated as
related to bowel perforation
- The incidence of serious AEs were 16.1%
(5/31) for usual care and 15.6% (7/45) for naloxegol 25 mg.
Discontinuations due to AEs with naloxegol were 13.3% (6/45).
Patients receiving usual care did not receive investigational
medication and therefore discontinuations for AEs were not
assessed
The most common adverse reactions with MOVANTIK as compared to
placebo in clinical trials were abdominal pain (21% vs. 7%),
diarrhea (9% vs. 5%), nausea (8% vs 5%), flatulence (6% vs 3%),
vomiting (5% vs 4%), headache (4% vs. 3%), and hyperhidrosis (3%
vs. <1%).
MOVANTIK is the first once-daily oral peripherally-acting
mu-opioid receptor antagonist (PAMORA) medication for the treatment
of OIC in adult patients with chronic, non-cancer pain. When
administered at recommended dose levels, MOVANTIK decreases the
constipating effect of opioids by blocking opioids from binding to
mu-receptors in the bowel. And because of its design, at
recommended doses, the CNS penetration of naloxegol is expected to
be negligible, limiting potential interference with centrally
mediated opioid analgesia.
IMPORTANT SAFETY INFORMATION ABOUT MOVANTIK
MOVANTIK™ (naloxegol) is contraindicated in:
- Patients with known or suspected
gastrointestinal (GI) obstruction and patients at increased risk of
recurrent obstruction, due to the potential for GI perforation
- Patients receiving strong CYP3A4
inhibitors (eg, clarithromycin, ketoconazole) because these
medications can significantly increase exposure to naloxegol which
may precipitate opioid withdrawal symptoms
- Patients with a known serious or severe
hypersensitivity reaction to MOVANTIK or any of its excipients
- Cases of GI perforation have been
reported with the use of another peripherally acting opioid
antagonist in patients with conditions that may be associated with
localized or diffuse reduction of structural integrity in the wall
of the GI tract. Monitor for severe, persistent, or worsening
abdominal pain; discontinue if this symptom develops
- Symptoms consistent with opioid
withdrawal, including hyperhidrosis, chills, diarrhea, abdominal
pain, anxiety, irritability, and yawning, occurred in patients
treated with MOVANTIK. Patients receiving methadone as therapy for
their pain condition were observed in the clinical trials to have a
higher frequency of GI adverse reactions that may have been related
to opioid withdrawal than patients receiving other opioids.
Patients with disruptions to the blood-brain barrier may be at
increased risk for opioid withdrawal or reduced analgesia. These
patients (eg, multiple sclerosis, recent brain injury, Alzheimer’s
disease, and uncontrolled epilepsy) were not enrolled in the
clinical studies. Take into account the overall risk-benefit
profile when using MOVANTIK in such patients. Monitor for symptoms
of opioid withdrawal when using MOVANTIK in such patients
- Avoid concomitant use of moderate
CYP3A4 inhibitors (eg, diltiazem, erythromycin, verapamil) because
they may increase the risk of adverse reactions. Use of strong
CYP3A4 inducers (eg, rifampin, carbamazepine, St. John’s Wort) is
not recommended because they may decrease the efficacy of MOVANTIK.
Avoid concomitant use of MOVANTIK with another opioid antagonist
due to the increased risk of opioid withdrawal
- The use of MOVANTIK during pregnancy
may precipitate opioid withdrawal in a fetus due to the immature
fetal blood-brain barrier. MOVANTIK should be used during pregnancy
only if the potential benefit justifies the potential risk to the
fetus. Due to the potential for serious adverse reactions,
including opioid withdrawal, in nursing infants, a decision should
be made to discontinue nursing or discontinue the drug, taking into
account the importance of the drug to the mother
- The most common adverse reactions with
MOVANTIK as compared to placebo in clinical trials were: abdominal
pain (21% vs. 7%), diarrhea (9% vs. 5%), nausea (8% vs 5%),
flatulence (6% vs 3%), vomiting (5% vs 4%), headache (4% vs. 3%),
and hyperhidrosis (3% vs. <1%)
Please see full US Prescribing
Informationhttp://www.azpicentral.com/movantik/movantik.pdf
NOTES TO EDITORS
About the KODIAC Clinical Program
The FDA approval of MOVANTIK was based on data from the KODIAC
clinical program, which is comprised of four studies: KODIAC-4, -5,
-7 and -8. KODIAC-4 and -5 were both placebo controlled,
double-blind, 12 week studies assessing safety and efficacy, while
KODIAC-7 was a 12 week safety extension to KODIAC-4, and KODIAC-8
was a 52 week long-term, open-label, safety study.
About MOVANTIK™ (naloxegol)
MOVANTIK™ (naloxegol) Tablets is the first FDA approved
once-daily oral peripherally-acting mu-opioid receptor antagonist
(PAMORA) specifically designed for the treatment of opioid-induced
constipation (OIC) in adult patients with chronic non-cancer pain.
In the Phase III clinical studies, MOVANTIK was administered as a
once-daily tablet and was designed to block the binding of opioids
to opioid receptors in tissues such as the gastrointestinal (GI)
tract.
MOVANTIK is part of the exclusive worldwide license agreement
announced on September 21, 2009 between AstraZeneca and Nektar
Therapeutics. MOVANTIK was developed using Nektar’s oral small
molecule polymer conjugate technology.
On March 19, 2015, AstraZeneca announced a co-commercialization
agreement with Daiichi Sankyo, Inc. for MOVANTIK in the US, in line
with the Company’s strategy of delivering value through its own
development and commercial capabilities as well as through external
collaboration.
About Daiichi Sankyo, Inc.
Daiichi Sankyo Group is dedicated to the creation and supply of
innovative pharmaceutical products to address the diversified,
unmet medical needs of patients in both mature and emerging
markets. While maintaining its portfolio of marketed
pharmaceuticals for hypertension, dyslipidemia and bacterial
infections used by patients around the world, the Group has also
launched treatments for thrombotic disorders and is building new
product franchises. Furthermore, Daiichi Sankyo research and
development is focused on bringing forth novel therapies in
oncology and cardiovascular-metabolic diseases, including
biologics. The Daiichi Sankyo Group has created a ‘Hybrid Business
Model’ to respond to market and customer diversity and optimize
growth opportunities across the value chain. For more information,
please visit: www.daiichisankyo.com. Daiichi Sankyo, Inc.,
headquartered in Parsippany, New Jersey, is a member of the Daiichi
Sankyo Group. For more information on Daiichi Sankyo, Inc., please
visit www.dsi.com.
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical
business that focuses on the discovery, development and
commercialization of prescription medicines, primarily for the
treatment of cardiovascular, metabolic, respiratory, inflammation,
autoimmune, oncology, infection and neuroscience diseases.
AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. For more
information please visit www.astrazeneca-us.com.
3120303 Last Updated 5/15
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