VENICE, Italy, June 23 /PRNewswire/ --
-- Efficacy and safety data were generally consistent with oral olanzapine with the exception of injection-related events
Results from olanzapine long-acting injection (LAI) clinical trials showed that the efficacy and safety profile of olanzapine LAI was generally consistent with that of Zyprexa(R) (olanzapine) with the exception of injection-related events. Results from a 24-week maintenance study (HGKA) and interim findings from an ongoing open-label study (HGKB) were presented at the first annual Schizophrenia International Research Society (SIRS) Conference in Venice, Italy.
Olanzapine LAI is an investigational formulation that combines olanzapine with a pamoate salt, resulting in an extended delivery of up to four weeks. Since olanzapine was introduced in 1996, it has been prescribed to approximately 24 million people worldwide.
"These studies offer insight into the potential of olanzapine LAI as a maintenance treatment for patients with schizophrenia who may have difficulty taking medication on a daily basis," said David McDonnell, M.D., clinical research physician at Lilly. "Schizophrenia is a challenging and complex disease to manage, which is why finding new ways to support patient compliance with medication is so important."
Regulatory reviews of olanzapine LAI applications are ongoing in the European Union, Canada, Australia and United States.
Notes for editors:
About HGKA (24-week maintenance of effect study)
In this 24-week double-blind maintenance study, a total of 1,065 adult outpatients with schizophrenia who had been stabilized previously on open-label oral olanzapine (10, 15, or 20 mg daily) for four to eight weeks were randomized to one of three therapeutic dosing regimens of olanzapine LAI (150 mg every two weeks, 405 mg every four weeks, or 300 mg every two weeks), or to a low reference dose of olanzapine LAI (45 mg every four weeks), or remained on oral olanzapine at their previously stabilized dose.
At the three higher doses, olanzapine LAI showed maintenance of treatment effect for schizophrenia for up to 24 weeks. Patients remained free of symptom exacerbation (relapse), as assessed by the Brief Psychiatric Rating Scale (BPRS), at a rate of 95 percent with 300 mg/two weeks, 90 percent with 405 mg/four weeks, and 84 percent with 150 mg/two weeks of olanzapine LAI. Comparatively, 93 percent of patients receiving oral olanzapine remained free of symptom exacerbation during the study. The 405 mg/four weeks and the pooled two-week dosing regimens showed non-inferiority when compared to oral olanzapine as well as to each other. All three higher olanzapine LAI doses had longer time to symptom exacerbation than the reference dose (all p<.01).
The safety profile for olanzapine LAI was consistent with that of oral olanzapine except for injection-related events. Incidence of weight gain of 7 percent or more from baseline was significantly higher for oral olanzapine (21.4 percent), olanzapine LAI 300 mg/two weeks (20.7 percent), olanzapine LAI 405 mg/four weeks (15.2 percent) and olanzapine LAI 150 mg/two weeks (16.4 percent) when compared with olanzapine LAI 45 mg/4 weeks (8.3 percent, all p less than or equal to .05). Adverse events reported in 5 percent or more of patients were insomnia, weight increase, anxiety, nasopharyngitis, somnolence and headache.
In HGKA, two patients experienced and recovered fully from Post-Injection Delirium/Sedation Syndrome (PDSS), which describes a range of signs and symptoms such as sedation, delirium, dizziness, confusion, disorientation, slurred speech and altered gait.
Across all olanzapine LAI clinical trials, PDSS events have been seen in 0.07 percent of injections and 1.4 percent of patients. As of 31 May, 2008, 29 events have been reported in 28 patients, all of whom have recovered fully. Given that awareness and recognition of these events are key aspects of identifying and minimizing them, Lilly has proposed a plan for managing PDSS risks that is comprised of a detailed product label, extensive healthcare provider training before product availability and an ongoing educational program.
About HGKB (160-week Interim Results of Open-label Extension Trial)
Adult patients with schizophrenia or schizoaffective disorder (n=931) were enrolled in this ongoing open-label trial of olanzapine LAI following participation in one of three randomized, controlled studies of olanzapine LAI. At study onset, patients received flexibly-dosed olanzapine LAI at intervals of approximately two to four weeks.
At the time of analysis, all patients had had the opportunity to be in the study for at least one year of open-label treatment; some had been enrolled for up to three years of treatment.
Treatment response was measured by the Clinical Global Impression Severity of Illness (CGI-S) scale, which examined severity of illness, global improvement and efficacy. Baseline-to-endpoint mean change on the CGI-S was -0.16, from a baseline of 2.92.
At 160 weeks, the discontinuation rate was low (39.6 percent). The most common reasons for discontinuation were that a patient withdrew consent (20.1 percent), experienced an adverse event (6.3 percent) or was lost to follow up (5.6 percent).
Adverse events reported in 5 percent or more of patients were increased weight, insomnia, somnolence, anxiety, headache, and nasopharyngitis. The mean weight change of study participants was an increase of 1.4 kilograms, with 28.1 percent of patients experiencing an increase of 7 percent or more in weight.
The percentage of patients with a fasting glucose increase from normal to high at any time was 4.7 percent. The percentage of patients with a random total cholesterol increase from normal to high at any time was 5.2 percent. The percentage of patients with a random triglycerides increase from normal to high at any time was 11.9 percent.
At the time of the interim analysis of HGKB, 23 PDSS events were reported in 22 patients. Between 30 September, 2007 and 31 May, 2008, four additional events have been reported in this ongoing trial.
About Long-acting Injectable Antipsychotic Medications
The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines state that poor or partial treatment compliance is a major problem in the long-term treatment of schizophrenia. Depot formulations should be considered as a treatment option when a patient expresses a preference for such treatment due to convenience or if it is determined that a depot formulation is necessary to help avoid nonadherence to oral medications.(i)
Long-acting antipsychotic formulations have been associated with improved treatment adherence and reduced treatment failures.(ii) By administering long-acting medications, healthcare professionals know when patients have received their medication and can immediately detect non-adherence when a patient fails to return for a scheduled injection.(iii) Different from both oral and injected short-acting formulations, long-acting formulations of antipsychotics allow for stable concentrations of the active drug to remain at a therapeutic range for an extended period of time.(iv)
About Schizophrenia
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