Eli Lilly and Company: New Data Show Nizatidine Cuts Weight Gain During Zyprexa Treatment By 50 Percent.

Business Editors, Health/Medical Writers

INDIANAPOLIS--(BW HealthWire)--May 2, 2001

New data presented today at The International Congress on Schizophrenia Research (ICSR) found that the use of 300 mg twice daily of nizatidine reduced treatment-emergent weight gain by approximately 50 percent among patients taking Zyprexa(R) (olanzapine, Lilly) for the treatment of schizophrenia. Nizatidine (Axid(R)), which is used to treat stomach and intestinal ulcers, was found to be safe and well-tolerated when used in combination with Zyprexa and did not significantly affect Zyprexa's efficacy. However, nizatidine is not approved for weight reduction, either alone or in combination with other medications.

Weight gain is commonly observed during treatment with antipsychotic medications. Data have shown that weight gain associated with Zyprexa stabilized over time and that patients with higher body mass had a reduced tendency to gain weight.

"Unfortunately, some patients who could benefit from Zyprexa may not be receiving it due to concerns about possible weight gain," said Alan Breier, M.D., Research Fellow and Leader, Zyprexa Product Team, Lilly Research Laboratories. "While research tells us that early intervention, including counseling patients to initiate and maintain positive diet and exercise habits, may reduce the potential for weight gain, we have also been looking at pharmacological approaches to assist in managing weight gain during treatment with psychotropic drugs. These data suggest that administering nizatidine 300 mg twice daily in combination with Zyprexa may offer physicians an acceptable medical option to accompany behavioral interventions when appropriate."

New data presented at ICSR were from a 16-week, double-blind study of 132 patients with schizophrenia, schizoaffective disorder or schizophreniform disorder. Following a 2 to 9 day screening period, all patients received open-labeled Zyprexa (5 to 20 mg/day, starting at 10 mg) and were randomized to receive 150 mg of nizatidine twice daily (N=45), 300 mg of nizatidine twice daily (N=43) or placebo (N=44).

At the 300 mg dose group of nizatidine, significant reduction in weight gain was seen as early as three weeks and was maintained out to 16 weeks, and weight gain appeared to plateau at eight weeks. After 16 weeks, Zyprexa-treated patients taking 300 mg twice daily (or 600 mg) of nizatidine gained significantly less weight (6.08 lbs.) than patients taking placebo (12.15 lbs.) Patients taking 150 mg twice daily (or 300 mg) of nizatidine also gained less weight (9.72 lbs.) compared to placebo but this result was not statistically significant.

Nizatidine was well-tolerated and did not significantly affect clinical outcomes. There were no significant differences in any adverse events reported between the three treatment groups. Somnolence was the most common adverse event across the three groups. Increased appetite was reported in 22.7 percent of placebo patients, 8.9 percent of patients taking 150 mg of nizatidine twice daily and 16.3 percent of patients taking 300 mg of nizatidine twice daily. Other adverse events included dizziness, headache, dry mouth, nausea and rhinitis.

"There's no doubt that Zyprexa is effective, and that's the most important factor to me in selecting a treatment," said Ronald J. Koshes, M.D., a Washington, DC, psychiatrist specializing in the treatment of chronic mental illness. "If my patient is experiencing a good clinical response to a medication but is gaining weight, I will try every other type of intervention before risking relapse or harmful side effects that may result in changing the medication. I don't want to move two steps forward, only to go back four, so I avoid changing medications unless absolutely necessary."

Nizatidine therapy is the first in a series of pharmacological interventions that Lilly is investigating to help patients prevent or reduce weight gain. "Physicians have told us weight gain is a concern," said Dr. Breier. "We recognize that some physicians may not be prescribing Zyprexa to patients as a result. Lilly is putting its 125 years of research experience behind helping to find a possible solution."

Zyprexa Background

Zyprexa is currently indicated for the treatment of schizophrenia, the short-term treatment of acute manic episodes associated with bipolar disorder and for the long-term therapy and maintenance of treatment response of schizophrenia. Zyprexa is the first atypical antipsychotic to prove its long-term effectiveness in patients with schizophrenia. Since Zyprexa was introduced in 1996, it has been prescribed to more than six million people worldwide.

In the original schizophrenia registration trials, Zyprexa was generally well tolerated. However, as with all medications, Zyprexa was associated with some side effects. In the original six-week, acute-phase schizophrenia trials, the most common treatment-emergent adverse event associated with Zyprexa was somnolence. Other common events were dizziness, weight gain, constipation, akathisia (restlessness) and postural hypotension. Modest elevations of prolactin were also seen, although mean changes from baseline to endpoint were not statistically significantly different between Zyprexa and placebo. A small number of patients experienced asymptomatic elevations of hepatic transaminase; none of these patients developed jaundice or drug-induced hepatitis.

In short-term (3- and 4-week) acute bipolar mania trials, the most common treatment-emergent adverse event associated with Zyprexa was somnolence. Other common events were dry mouth, dizziness, asthenia, constipation, dyspepsia, increased appetite and tremor.

Nizatidine Background

Nizatidine is indicated for the treatment of stomach and intestinal ulcers. It is not approved for weight reduction, either alone or in combination with other medications. Nizatidine was found to be generally safe and well-tolerated in clinical trials. However, the incidence rates of adverse events in clinical trials between patients treated with nizatidine versus placebo were statistically significant for anemia (0.2% vs. 0%) and urticaria (0.5% vs. 0.1%), but were not statistically significant for the most commonly reported adverse events, which were headache (16.6% vs. 15.6%) and diarrhea (7.2% vs. 6.9%). The dosage should be reduced in patients with moderate to severe renal insufficiency and in some elderly patients.

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. Additional information about Lilly is available at www.lilly.com.

Zyprexa(R)(olanzapine, Lilly)

Axid(R) (nizatidine, Lilly), Reliant Pharmaceuticals LLC