New Data Show Duloxetine Maintained Pain Reduction For More Than Six Months In Patients With Diabetic Peripheral Neuropathic Pain

Main Category: Pain / Anesthetics
Also Included In: Diabetes;  Clinical Trials / Drug Trials
Article Date: 20 Aug 2008 - 4:00 PDT

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Duloxetine hydrochloride maintained pain reduction in the treatment of diabetic peripheral neuropathic pain (DPNP) for more than six months,[i] according to new data presented today at the 12th World Congress on Pain in Glasgow, Scotland.

The open-label study, which aimed to evaluate long-term maintenance of effect of duloxetine 60 mg once daily, is the first to assess the efficacy of duloxetine in DPNP beyond three months. The study enrolled 216 patients with DPNP who began eight weeks of treatment with 60 mg of duloxetine once daily. Over this initial eight-week period, 53 percent (N=115) of enrolled patients experienced clinically significant improvement in pain reduction (defined as at least 30 percent pain reduction) as measured by the Brief Pain Inventory (BPI) 24-hour average pain rating.1 This group of responders was maintained on duloxetine 60 mg (N=103) once daily for up to 26 weeks to evaluate sustained pain reduction. Results at study end showed that the reduction in pain was maintained in 74.8 percent (N=77) of the sustained responders with 60 mg duloxetine over the full study period.

"DPNP is a chronic, potentially disabling, condition requiring treatment over a long period of time," said Vladimir Skljarevski, M.D., lead author of the study and a neurologist and medical fellow at Lilly Research Laboratories. "This study showed duloxetine reduced pain over a six-month period, making this the longest data analysis of duloxetine for the treatment of DPNP."

During the course of the eight-week acute therapy and 26-week maintenance therapy periods, the most common treatment-emergent adverse events (those occurring in more than 5 percent of patients) for those taking 60 mg of duloxetine were nausea, somnolence, hyperhydrosis (excessive sweating), dry mouth, anorexia, asthenia (weakness), fatigue and headache.[ii]

An estimated 246 million adults worldwide suffer from diabetes.[iii] By 2025, that number is expected to rise to 380 million, according to the International Diabetes Federation.3Although all diabetics are at risk for DPNP, those most likely to develop the condition are long-term sufferers whose blood-sugar levels have not been adequately controlled, who have high blood pressure or are overweight.[iv] An estimated 17.2 million to 49.2 million patients with diabetes have been diagnosed with DPNP.[v]

Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI). Although it does not treat the underlying nerve damage caused by DPNP, duloxetine does help relieve the intense pain often associated with the disorder.[vi] Scientists believe it does this by increasing levels of serotonin and norepinephrine - two neurotransmitters believed to regulate a person's sensitivity to pain. Increasing these levels in a balanced way is thought to improve the body's natural ability to regulate pain by modulating the descending pain pathways in the central nervous system.

In Europe, duloxetine is approved for the treatment of DPNP, major depressive disorder (MDD) and generalised anxiety disorder (GAD).

Duloxetine is approved in various countries outside of Europe for the management of DPNP, for the treatment of MDD, for the treatment of GAD and for the management of fibromyalgia.

About Diabetic Peripheral Neuropathic Pain

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.4 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 Duloxetine

While duloxetine's mechanism of action in humans is not fully known, it is believed to affect both serotonin and norepinephrine/noradrenaline mediated nerve signalling in the brain and the spinal cord. Based on pre-clinical studies, duloxetine is a reuptake inhibitor of serotonin and norepinephrine/noradrenaline. Scientists believe its effect on pain perception is due to increasing the activity of serotonin and norepinephrine in the central nervous system.

Duloxetine is approved for the treatment of major depressive disorder and diabetic peripheral neuropathic pain in many countries and is approved in some countries for the treatment of stress urinary incontinence and generalised anxiety disorder. Duloxetine is approved only for adults age 18 and over. There is a possibility of an increased risk of suicidal thoughts or behaviour in children and young adults treated with antidepressants. Patients should call their doctor right away if they experience worsening depression symptoms, unusual changes in behaviour or thoughts of suicide, especially at the beginning of treatment or after a change in dose.

Patients taking duloxetine may experience dizziness or fainting upon standing.

The most common side effects of duloxetine include:

- for depression: nausea, dry mouth, headache, insomnia and diarrhea
- for diabetic peripheral neuropathic pain: nausea, somnolence (sleepiness), fatigue, headache and dizziness
- for generalised anxiety disorder: nausea, fatigue, dry mouth, drowsiness, constipation, insomnia, decreased appetite, hyperhydrosis, decreased libido, vomiting, ejaculation delay and erectile dysfunction.
- for stress urinary incontinence: nausea, dry mouth and fatigue

This is not a complete list of side effects.

Duloxetine is contraindicated in patients who are allergic to it, who have liver disease resulting in hepatic impairment, who are taking a monoamine oxidase inhibitor (MAOI), fluvoxamine, ciprofloxacin or enoxacine or who have severe kidney disease. The initiation of treatment with duloxetine also is contraindicated in patients with uncontrolled hypertension that could expose patients to a potential risk of hypertensive crisis. Additional information about Lilly is available at http://www.lilly.co.uk

Eli Lilly and Company and Boehringer Ingelheim

In November 2002, Eli Lilly and Company and Boehringer Ingelheim signed a long-term agreement to jointly develop and commercialize duloxetine hydrochloride. This partnership covers neuroscience indications in most countries outside of the United States and Japan, with a few exceptions.

About Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of 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.

About Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 135 affiliates in 47 countries and almost 38,900 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine. In 2007, Boehringer Ingelheim posted net sales of 10.9 billion euro while spending one-fifth of net sales in its largest business segment Prescription Medicines on research and development. For more information please visit http://www.boehringer-ingelheim.com

Duloxetine for major depressive episodes and diabetic peripheral neuropathic pain is marketed by Lilly and Boehringer Ingelheim in all countries included in the partnership under the brand name Cymbalta, except for Germany, Greece, Italy and Spain. In Germany, Lilly and Boehringer Ingelheim market duloxetine for major depressive episodes under the brand name Cymbalta, and market the product for diabetic peripheral neuropathic pain as Ariclaim®. In Greece, Italy and Spain, Lilly markets the product as Cymbalta, and Boehringer Ingelheim markets the product as Xeristar®. In the United States, Cymbalta is marketed by Lilly and Quintiles. In Japan, duloxetine is co-developed and co-marketed by Lilly and Shionogi & Co., Ltd.

Duloxetine for stress urinary incontinence is marketed by Lilly under the brand name Yentreve®.

References

[i] Skljarevski, V. et al. Evaluating the Maintenance of Effect of Duloxetine in Patients with Diabetic Peripheral Neuropathic Pain. Poster presented at the Annual World Congress of Pain. 19 August 2008

[ii] Skljarevski, V. et al. Maintenance of Effect of Duloxetine 60 mg Once Daily in Patients With Diabetic Peripheral Neuropathic Pain. HMEM. Eli Lilly Research Laboratories.

[iii] IDF. Diabetes Prevalence. International Diabetes Federation.Available at http://www.idf.org/home/index.cfm?node=264. Accessed 24 June 2008.

[iv] National Diabetes Information Clearinghouse, Diabetic Neuropathies: The Nerve Damage of Diabetes. National Institute of Diabetes and Digestive and Kidney Disease. Available at http://www.diabetes.niddk.nih.gov/dm/pubs/neuropathies/, Accessed 24 June 2008.

[v] Tesfaye S. and Kempler P. Painful Diabetic Neuropathy. Diabetologia. 2005; 48: 805-807

[vi] Wernicke JF, Lu Y, D'Souza DN, Waninger A, Tran PV. Duloxetine at doses of 60 mg QD and 60 mg BID is effective treatment of diabetic neuropathic pain. Paper presented at: American Academy of Neurology; April 24-May 1, 2004; San Francisco, CA.

Boehringer Ingelheim