Patients Taking Cymbalta(R) Experienced Reduced Chronic Low Back Pain in New Study

INDIANAPOLIS, Aug. 25  /PRNewswire/ -- Data from a new study suggest that Cymbalta (duloxetine HCl) 60-120 mg once daily significantly reduced chronic low back pain, as measured by the Brief Pain Inventory (BPI) 24-hour average pain score, compared with placebo.(1) Results from the double-blind, 13-week, placebo-controlled study of 236 patients were presented today at the annual congress of the European Federation of Neurological Societies (EFNS) in Madrid, Spain.

Duloxetine-treated patients reported significantly greater reduction in pain scores than placebo-treated patients. Thirty-one percent of duloxetine-treated patients experienced a 50 percent reduction in pain, compared with 19 percent of placebo-treated patients, as measured by an 11-point Likert pain scale. Physicians consider a pain reduction of at least 30 percent as clinically significant.(2)

Treatment with duloxetine also was associated with improved patient outcomes as measured by the Patient Global Impressions of Improvement (PGI-I), and physical functioning as measured by the Roland Morris Disability Questionnaire (RMDQ-24).

Significantly more patients in the duloxetine group discontinued because of adverse events. In this study, the most common adverse events (those occurring in more than 5 percent of patients in the duloxetine group) were nausea, dry mouth, fatigue, diarrhea, excessive sweating (hyperhidrosis), dizziness and constipation. Adverse events were similar to those seen in previous duloxetine studies in other disease states.

"Chronic low back pain can have a significant impact on a person's ability to do the things they enjoy," said Vladimir Skljarevski, lead study author and a neurologist and medical fellow at Lilly Research Laboratories. "This research may offer hope to those dealing with this debilitating condition."

  Additional Study Highlights
  -- The repeated measures analysis using the patient diary demonstrated a
     significantly greater reduction in pain in the first week after
     starting the 60 mg daily dose, which continued throughout the 13 weeks
     of the acute therapy phase.
  -- Superiority to placebo in most secondary analyses including eight out
     of the remaining 10 BPI items (e.g., weekly 24-hour average pain score,
     weekly 24-hour worst pain and weekly 24-hour night pain) was observed.
     -- Superiority to placebo was not observed in two BPI items: pain
        interference with general activity and pain interference with sleep.
  -- Statistically significant differences in three individual items in the
     Short Form-36 of the Medical Outcomes Study (SF-36) - bodily pain,
     general health and vitality - were observed.
     -- Statistically significant differences were not observed in the
        remaining items in the Short Form-36 of the Medical Outcomes Study,
        including mental component summary, physical component summary,
        mental health, physical functioning, role-emotion, role-physical and
        social functioning.
  -- The duloxetine treatment group experienced a significantly greater
     improvement on the work-activity impairment score compared with the
     placebo treatment group as measured by the Work Productivity and
     Impairment Scale (WPAI).


  Study Methods


Adult patients given duloxetine (n=115) and those given placebo (n=121) with a history of non-neuropathic chronic low back pain for more than six months with a weekly mean 24-hour average pain score greater than or equal to 4 at baseline (0-10 scale) and without major depressive disorder were initially treated with duloxetine 60 mg once daily for the first seven weeks in this randomized placebo-controlled trial. After seven weeks of duloxetine treatment, patients reporting less than 30 percent pain reduction (non-responders) had their dose increased to 120 mg once daily. Responders continued on 60 mg once daily. The study's primary objective was the reduction of the BPI 24-hour average pain score. Secondary measures included RMDQ-24, PGI-I, BPI Severity portion (BPI-S) and BPI Interference portion (BPI-I), diary-based weekly mean of the 24-hour average pain score, Clinical Global Impression of Severity (CGI-S), and response rates. Health outcomes, safety and tolerability also were assessed. Continuous efficacy variables were analyzed using analysis-of-variance (ANOVA) with treatment and investigator in the model, or analysis of covariance, with baseline, treatment and investigator in the model, and the stratifying variable of NSAID use (Yes/No). Mixed-model repeated measures (MMRM) analysis also was used to measure improvement at all time points. Treatment groups were compared based on the difference between least-squares means using two-sided testing at the 0.05 significance level. Safety analyses were conducted to compare treatment groups using Fisher's exact test.

Duloxetine data also presented at 12th World Congress of Pain

Data from a separate duloxetine chronic low back pain study were presented on Aug. 21 at the 12th World Congress of Pain in Glasgow, Scotland. At study endpoint, duloxetine did not significantly differ from placebo on the primary measure of weekly mean 24-hour average pain score.(3) However, patients taking duloxetine 60 mg once daily showed significant pain reductions compared with placebo from week three through week 11 of the 13-week trial.(3) This was the first study designed to assess the effect of duloxetine on the reduction of chronic low back pain compared with placebo.

In the 13-week, double-blind, randomized, placebo-controlled study (n=404), patients taking duloxetine 60 mg once daily experienced statistically significant improvements in several secondary outcome measures compared with placebo. Patients taking duloxetine 60 mg once daily also experienced a statistically significant improvement in patient outcomes as measured by the PGI-I and physical functioning as measured by the RMDQ-24.(3) In this study, the most common adverse events (those occurring in more than 5 percent of patients in the duloxetine group) were nausea, insomnia, dry mouth, constipation, headache, diarrhea, dizziness, somnolence (drowsiness) and fatigue.

It is estimated that at least 15 million adults in the United States have chronic low back pain.(4) According to the International Association for the Study of Pain (IASP), pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.(5) Chronic pain is defined as pain that persists beyond acute pain or beyond the expected time for an injury to heal.(6) Men and women are equally affected by chronic low back pain, and it occurs most often between ages 30 and 50.(7)

About Cymbalta

Serotonin and norepinephrine in the brain and spinal cord are believed to both mediate core mood symptoms and help regulate the perception of pain. Based on preclinical studies, Cymbalta is a balanced and potent reuptake inhibitor of serotonin and norepinephrine that is believed to potentiate the activity of these chemicals in the central nervous system (brain and spinal cord). While the mechanism of action of Cymbalta is not fully known, scientists believe its effects on depression and anxiety symptoms, as well as its effect on pain perception, may be due to increasing the activity of serotonin and norepinephrine in the central nervous system.

Cymbalta is approved in the United States for the acute and maintenance treatment of major depressive disorder, the acute treatment of generalized anxiety disorder, and the management of fibromyalgia and diabetic peripheral neuropathic pain in adults age 18 years and older. Cymbalta is not approved for use in pediatric patients.

Important Safety Information

Cymbalta is approved to treat major depressive disorder and generalized anxiety disorder, and to manage diabetic peripheral neuropathic pain and fibromyalgia. Antidepressants can increase suicidal thoughts and behaviors in children, adolescents, and young adults. Patients should call their doctor right away if they experience new or worsening depression symptoms, unusual changes in behavior, or thoughts of suicide. Be especially observant within the first few months of treatment or after a change in dose. Cymbalta is approved only for adults 18 and over.

Cymbalta is not for everyone. Patients should not take Cymbalta if they have recently taken a type of antidepressant called a monoamine oxidase inhibitor (MAOI), are taking Mellaril(R) (thioridazine), or have uncontrolled glaucoma. Patients should speak with their doctor about any medical conditions they may have including kidney problems, glaucoma, or diabetes. Patients should talk to their doctor if they have itching, right upper belly pain, dark urine, yellow skin or eyes, or unexplained flu-like symptoms, which may be signs of liver problems. Severe liver problems, sometimes fatal, have been reported. They should also talk to their doctor about alcohol consumption. Patients should tell their doctor about all their medicines, including those for migraine, to avoid a potentially life-threatening condition. Taking Cymbalta with NSAID pain relievers, aspirin, or blood thinners may increase bleeding risk. Patients should consult with their doctor before stopping Cymbalta or changing the dose and if they are pregnant or nursing.

Patients taking Cymbalta may experience dizziness or fainting upon standing. The most common side effects of Cymbalta include nausea, dry mouth, sleepiness, and constipation. This is not a complete list of side effects.

For full Patient Information, visit http://www.cymbalta.com/.

For full Prescribing Information, including Boxed Warning and medication guide, visit http://www.cymbalta.com/.

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 chronic pain including the management of chronic low back pain 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) Skljarevski, V. et al. Efficacy of Duloxetine in Chronic Low Back Pain.  Poster presented at the European Federation of Neurological Societies Annual Congress. 25 August 2008.

(2) Farrar JT, JP Young Jr., L LaMoreaux, JL Werth, RM Poole.  Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale.  2001.  Pain (94):149-158.

(3) Skljarevski, V. et al. Duloxetine versus Placebo in the Treatment of Chronic Low Back Pain.  Poster presented at the 12th World Congress of Pain. 21 August 2008.

(4) Praemer A, Furnes S, Rice DP. Musculoskeletal conditions in the United States. Rosemont: AAUS, 1992: 1-99.

(5) International Association for the Study of Pain. "IASP Pain Terminology" Available at: http://www.iasp-/ pain.org/AM/Template.cfm?Section=General_Resource_Links&Template=/CM/HTMLDispl ay.cfm&ContentID=3058#Pain. Accessed on 5/27/08.

(6) American Pain Society. "Pain Control in the Primary Care Setting." 2006:15.

(7) National Institute of Neurological Disorders and Stroke.  "Low Back Pain Fact Sheet."  Available at: http://www.ninds.nih.gov/disorders/backpain/detail_backpain.htm.  Accessed on June 25, 2008.

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DATASOURCE: Eli Lilly and Company



CONTACT:  Sonja Popp-Stahly of Eli Lilly and Company, [phone],

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