Study Finds Cymbalta(R) Was As Safe And Well-Tolerated As Routine Drug Treatments For Diabetic Nerve Pain
February 14 2006 - 7:00AM
PR Newswire (US)
Cymbalta Patients Functioned As Well As Those Switching Or Adding
Therapies INDIANAPOLIS, Feb. 14 /PRNewswire-FirstCall/ -- A
long-term study of more than 200 patients found that Cymbalta
(duloxetine HCl) is as safe and well- tolerated as current routine
care that uses one or more medications for the management of pain
caused by diabetic nerve damage. Study findings also show that
Cymbalta did not adversely affect the progression of diabetes or
many of the complications associated with the illness, such as
damage to the nerves, kidneys and eyes. The findings, published in
the current issue of the Journal of Palliative Medicine, "suggest
that with Cymbalta, clinicians can expect a similar level of
quality of life without compromising safety or tolerability,"
explained Dr. Tim Smith, a study author and clinical instructor of
medicine at Washington University School of Medicine. The 52-week
study compared Cymbalta, a non-narcotic prescription medication for
the management of diabetic nerve pain, to routine care, defined as
therapies that the investigator and the patient believed permitted
the optimal benefit to the patient, such as anticonvulsants and
antidepressants. The most commonly used prescription pain
medications for routine care included Neurontin(R) (gabapentin),
Elavil(R) (amitriptyline) and Effexor-XR(R) (venlafaxine extended
release). Diabetic management in both the routine care- treated and
Cymbalta-treated groups was adjusted at the discretion of the
investigator. The data found no significant differences in the
overall incidence of either adverse events resulting from treatment
or quality of life measures in patients taking Cymbalta compared to
those receiving routine care. While the majority of people with
diabetes experience symptoms associated with diabetic neuropathy,
such as peripheral neuropathic pain in the toes, feet, legs, hands,
arms and fingers, only three million Americans have been
diagnosed.(1) Diabetic nerve pain can make simple acts like putting
on a shoe or walking nearly impossible. The pain typically worsens
at night, also making it difficult to sleep.(2,3) All of these
symptoms can leave many patients debilitated, unable to participate
in normal daily activities, socialize, or keep a job. While the
study design allowed the routine care group to switch and add
therapies to find a more effective or better-tolerated treatment,
the Cymbalta group was much less flexible. Despite this
disadvantage, 72 percent of patients treated with Cymbalta remained
on treatment, compared with 82 percent of the routine care group --
a difference that was not statistically significant. "Patients with
diabetic nerve pain often switch or increase current or add
additional medications if their treatments are not offering relief,
are causing intolerable side effects, or are worsening their
diabetic complications," said Dr. Joel Raskin, the study's lead
author and medical fellow at Eli Lilly and Company. "In this study,
Cymbalta was shown to be a good treatment option that does not
appear to significantly affect management of their disease and may
help them resume their normal day-to-day activities." Additional
Study Highlights * In comparison to the Cymbalta-treated patients:
-- Significantly more routine care-treated patients experienced
these treatment emergent adverse events (TEAEs): pain in extremity
(15.8 percent vs. 6.2 percent), peripheral edema (15.8 percent vs.
5.0 percent), balance disorder (5.3 percent vs. 0.6 percent),
erythema, feeling abnormal and localized infections (3.9 percent
vs. 0 percent). -- A significantly greater percentage of routine
care-treated patients experienced one or more serious adverse
events (SAE) (28.9 percent vs. 16.8 percent). -- Significantly less
routine care patients discontinued due to adverse events (5.3
percent vs. 10.6 percent). * In routine care-treated patients, the
TEAEs reported by 10 percent or more of patients were peripheral
edema and pain in extremity (15.8 percent), somnolence (14.5
percent), and dizziness (13.2 percent). * In Cymbalta-treated
patients, the TEAE reported by 10 percent or more of patients was
nausea (10.6 percent). * No clinically significant therapy-group
differences were observed between the Cymbalta- and routine
care-treated groups in hemoglobin A1c (0.00 mg/dL plus or minus
0.01 vs. 0.00 mg/dL plus or minus 0.01) and diabetic complications,
including progression of retinopathy, neuropathy (0.43 vs. 0.60
points on the Michigan Neuropathy Screening Instrument (MNSI)
scale) or nephropathy (microalbumin/creatinine ratio, mean change
of 0.05 vs. 0.01). -- There was also a statistically, but not
clinically, significant increase in fasting glucose in the
Cymbalta-treated group, compared to the routine care-treated group
(0.30 plus or minus 4.34 vs. -0.82 plus or minus 4.45, p=0.016). *
Cymbalta-treated patients experienced a slight but statistically
significant increase in sitting diastolic blood pressure and pulse
(mean changes [SD]: 1.39 [10.71]) and 1.70 [11.82]) compared with
routine care- treated patients, who experienced a slight mean
decrease in pulse (mean change [SD]: -2.30 [11.29]). Methods This
study met its primary endpoints, which were to evaluate the safety
of Cymbalta over a 52-week open-label extension period, to evaluate
the safety of Cymbalta for up to 65 weeks with regard to the
progression of diabetic complications, and to assess the impact of
Cymbalta treatment and routine care on patient-reported health
outcomes. In this trial, 237 patients 18 years and older, with an
average age of 60 years, diagnosed with diabetic nerve pain
completed a 13-week acute therapy stage. They were randomly
assigned in a 2:1 ratio to therapy with 161 patients receiving
Cymbalta 60 mg twice daily and 76 patients receiving routine care.
Routine care consisted primarily of gabapentin, amitriptyline and
venlafaxine. Comparisons with individual therapies were not
possible based on the study design. Safety was measured by
discontinuation rates, TEAEs, laboratory assessments including
lipid profile and glycosylated hemoglobin (HbA1c), weight and
electrocardiograms. Health outcome measures were collected by
patient-report using the 36-item Short Form Health Survey (SF-36)
and the EuroQoL Questionnaire-Version 5-D (EQ-5D). Progression of
neuropathy was measured by the MNSI. Progression of retinopathy was
measured using ophthalmology assessments, including visual acuity.
Progression of nephropathy was measured by the
microalbumin/creatinine ratio. About Diabetic Peripheral Neuropathy
According to the National Institute of Diabetes & Digestive
& Kidney Diseases, approximately half of those with diabetes
have some form of nerve damage, or neuropathy, but not all will
develop symptoms. While nerve problems can occur at any time, the
highest rates are among those who have had diabetes for at least 25
years. People who have had problems controlling their blood sugar
levels, have high blood pressure, are overweight, have high levels
of blood fat, or are over the age of 40, may also have a greater
risk of developing diabetic peripheral neuropathy. Symptoms can
include numbness, tingling or pain and weakness in the toes, feet,
legs, hands, arms and fingers. These symptoms are often worse at
night.(4) About Cymbalta "Cymbalta is believed to modulate both
serotonin and norepinephrine in the brain and the spinal cord,
impacting nerve signaling. Based on pre-clinical studies, Cymbalta
is a balanced and potent reuptake inhibitor of serotonin and
norepinephrine. While the mechanism of action of duloxetine in
humans is not fully known, scientists believe its effect on pain
perception is due to increasing the activity of serotonin and
norepinephrine in the central nervous system." Cymbalta is approved
in the United States for the treatment of major depressive disorder
and the management of diabetic peripheral neuropathic pain, both in
adults. Cymbalta is not approved for use in pediatric patients.
Important Safety Information In clinical studies, antidepressants
increased the risk of suicidal thinking and behavior in children
and adolescents with depression and other psychiatric disorders.
Anyone considering the use of Cymbalta or any other antidepressant
in a child or adolescent must balance the risk with the clinical
need. Patients who are starting therapy should be observed closely
for worsening depression symptoms, suicidal thoughts or behavior,
or unusual changes in behavior. Cymbalta is not approved for use in
patients under the age of 18. Patients on antidepressants and their
families or caregivers should watch for worsening depression
symptoms, unusual changes in behavior and thoughts of suicide, as
well as for anxiety, agitation, panic attacks, difficulty sleeping,
irritability, hostility, aggressiveness, impulsivity, restlessness,
or extreme hyperactivity. Call the doctor if you have thoughts of
suicide or if any of these symptoms are severe or occur suddenly.
Be especially observant at the beginning of antidepressive
treatment or whenever there is a change in dose. Prescription
Cymbalta is not for everyone. People who are allergic to Cymbalta
or the other ingredients in Cymbalta should not take it. If you
have recently taken a type of antidepressant called a monoamine
oxidase inhibitor (MAOI), are taking Mellaril(R) (thioridazine) or
have uncontrolled narrow- angle glaucoma, you should not take
Cymbalta. Talk with your doctor before taking Cymbalta if you have
liver or kidney problems, glaucoma or consume large quantities of
alcohol. Women who are pregnant should talk with their doctor
before taking Cymbalta. Nursing while taking Cymbalta is not
recommended. Tell your doctor if you are taking other prescription
or nonprescription medications. In clinical studies of Cymbalta for
depression, the most common side effects were nausea, dry mouth,
constipation, decreased appetite, fatigue, sleepiness, and
increased sweating. Nausea was the most common side effect. For
most people, the nausea was mild to moderate, and usually subsided
within one-to-two weeks. Cymbalta is also approved for the
management of neuropathic pain associated with diabetic peripheral
neuropathy. In clinical studies of Cymbalta in these patients, the
most common side effects were nausea, sleepiness, dizziness,
constipation, dry mouth, increased sweating, decreased appetite,
and loss of strength or energy. In all clinical trials, most people
were not bothered enough by side effects to stop taking Cymbalta.
Your doctor may periodically check your blood pressure. Don't stop
taking Cymbalta without talking to your doctor. For full Patient
Information, visit http://www.cymbalta.com/. For full Prescribing
Information, including Boxed Warning, visit
http://www.cymbalta.com/. Neurontin is a registered trademark of
Pfizer Inc. Elavil is a registered trademark of AstraZeneca.
Effexor-XR is a registered trademark of Wyeth Pharmaceuticals Inc.
About Eli Lilly and Company Lilly, a leading innovation-driven
corporation, is developing a growing portfolio of first-in-class
and best-in-class pharmaceutical products by applying the latest
research from its own worldwide laboratories and from
collaborations with eminent scientific organizations. Headquartered
in Indianapolis, Ind., Lilly provides answers -- through medicines
and information -- for some of the world's most urgent medical
needs. Additional information about Lilly is available at
http://www.lilly.com/. P-LLY This press release contains
forward-looking statements about the potential of Cymbalta for the
treatment of DPNP, and reflects Lilly's current beliefs. However,
as with any pharmaceutical product, there are substantial risks and
uncertainties in the process of development and commercialization.
There is no guarantee that the product will continue to be
commercially successful. For further discussion of these and other
risks and uncertainties, see Lilly's filings with the United States
Securities and Exchange Commission. Lilly undertakes no duty to
update forward-looking statements. 1. "American Diabetes
Association Survey Finds Most People with Diabetes Don't Know About
Highly Prevalent, Serious Complication." Available at
http://www.diabetes.org/for-media/2005-press-releases/diabeticneuropathy.jsp.
Accessed on October 5, 2005. 2. National Institute of Neurological
Disorders and Stroke, "Peripheral Neuropathy Fact Sheet." Available
at:
http://www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuro
pathy.htm. Accessed on October 5, 2005. 3. Foundation for Health in
Aging, "Diabetic Neuropahy." Available at:
http://www.healthinaging.org/public_education/diabetes/neuropathy.php.
Accessed on October 5, 2005. 4. National Diabetes Information
Clearinghouse. Diabetic Neuropathies: The Nerve Damage of Diabetes.
National Institute of Diabetes and Digestive and Kidney Diseases.
http://www.diabetes.niddk.nih.gov/dm/pubs/neuropathies/, August
2004. (Logo: http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO )
First Call Analyst: FCMN Contact: terrafox@lilly.com
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO DATASOURCE:
Eli Lilly and Company CONTACT: Carole Puls (US), +1-317-277-1421,
pager: +1-888-431-8355, David Shaffer (OUS), +1-317-651-3710,
pager: +1-877-656-9084, both of Eli Lilly and Company
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