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.
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
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
Schizophrenia is a severe and debilitating illness with symptoms such
as delusions (false beliefs that cannot be corrected by reason),
hallucinations (usually in the form of non-existent voices or visions),
disorganized speech and severe disorganized or catatonic behavior. These
signs and symptoms are associated with marked social or occupational
dysfunction. Features of schizophrenia consist of characteristic signs and
symptoms that have been present for a significant portion of time during a
one-month period, with some signs of the disorder persisting for at least
six months.(v) In addition to these symptoms, patients with schizophrenia
are at greater risk for medical comorbidities than the general population.
About Olanzapine
Olanzapine is indicated in the United States for the treatment of
schizophrenia, acute mixed and manic episodes of bipolar disorder, and
maintenance treatment of bipolar disorder. In Europe, olanzapine is
indicated for the treatment of schizophrenia and olanzapine is effective in
maintaining the clinical improvement during continuation therapy in
patients who have shown an initial treatment response. Olanzapine is also
indicated in patients whose manic episode has responded to olanzapine
treatment and it is indicated for the prevention of recurrence in patients
with bipolar disorder.
Since olanzapine was introduced in 1996, it has been prescribed to
approximately 24 million people worldwide. Olanzapine is not approved for
patients under 18 years of age.
Hyperglycemia, in some cases extreme and associated with ketoacidosis
or hyperosmolar coma or death, has been reported in patients treated with
atypical antipsychotics, including olanzapine. While relative risk
estimates are inconsistent, the association between atypical antipsychotics
and increases in glucose levels appears to fall on a continuum and
olanzapine appears to have a greater association than some other atypical
antipsychotics. Physicians should consider the risks and benefits when
prescribing olanzapine to patients with an established diagnosis of
diabetes mellitus, or who have borderline increased blood glucose level.
Patients taking olanzapine should be monitored regularly for worsening of
glucose control. Persons with risk factors for diabetes who are starting on
atypical antipsychotics should undergo baseline and periodic fasting blood
glucose testing. Patients who develop symptoms of hyperglycemia during
treatment should undergo fasting blood glucose testing.
Undesirable alterations in lipids have been observed with olanzapine
use. Clinical monitoring, including baseline and follow-up lipid
evaluations in patients using olanzapine, is advised. Significant, and
sometimes very high, elevations in triglyceride levels have been observed
with olanzapine use.
Potential consequences of weight gain should be considered prior to
starting olanzapine. Patients receiving olanzapine should receive regular
monitoring of weight.
As with all antipsychotic medications, a rare and potentially fatal
condition known as Neuroleptic Malignant Syndrome (NMS) has been reported
with olanzapine. If signs and symptoms appear, immediate discontinuation is
recommended. Clinical manifestations of NMS are hyperpyrexia, muscle
rigidity, altered mental status and evidence of autonomic instability
(irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac
dysrhythmia). Additional signs may include elevated creatinine
phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure.
Also, as with all antipsychotic treatment, prescribing should be
consistent with the need to minimize Tardive Dyskinesia (TD). The risk of
developing TD and the likelihood that it will become irreversible are
believed to increase as the duration of treatment and the total cumulative
dose of antipsychotic increase. The syndrome may remit, partially or
completely, if antipsychotic treatment is withdrawn.
Other potentially serious adverse events include low blood pressure,
seizures, elevated prolactin levels, elevated liver enzymes, cognitive and
motor impairment, body temperature elevation, and trouble swallowing.
The most common treatment-emergent adverse event associated with
Zyprexa in placebo-controlled, short-term schizophrenia and bipolar mania
trials was somnolence. Other common events were dizziness, weight gain,
personality disorder (COSTART term for nonaggressive objectionable
behavior), constipation, akathisia, postural hypotension, dry mouth,
asthenia, dyspepsia, increased appetite and tremor.
About Lilly
Lilly (NYSE: LLY), 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
lilly.
P-LLY
This press release contains forward-looking statements about the safety
and efficacy of olanzapine long acting injection (LAI) and reflects Lilly's
current beliefs. However, as with any investigational pharmaceutical
product, there are substantial risks and uncertainties in the process of
research, development, regulatory milestones and commercialization. There
is no guarantee that olanzapine LAI will be approved for the treatment of
schizophrenia or that if approved, it will 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.
References
(i) Falkai P., Wobrock T., Lieberman J., Glenthoj B.,Gattaz W.F.,
Moller H.J & Wfsbp Task Force On Treatment Guidelines For Schizophrenia.
The World Journal of Biological Psychiatry, 2006; 7(1): 5/40.
(ii) Maxine X. Patel and Anthony S. David. Why aren't depot
antipsychotics prescribed more often and what can be done about it?
Advances in Psychiatric Treatment (2005) 11: 203-211.
(iii) Kane J.M et al. Guidelines for depot antipsychotic treatment in
schizophrenia. European Neuropsychopharmacology, Volume 8, Number 1, 1
February 1998, pp. 55-66(12). p. 58.
(iv) Maxine X. Patel and Anthony S. David. Why aren't depot
antipsychotics prescribed more often and what can be done about it?
Advances in Psychiatric Treatment (2005) 11: 203-211.
(v) American Psychiatric Association. Diagnostic and Statistical Manual
of Mental Disorders, forth edition, 2000, pp. 298.
Eli Lilly and Company
lilly
View drug information on Zyprexa.
We Recommend:
• Buy Cheap Stavudine
• Buy Atripla Online Without Prescription
• Buy Atripla No Prescription
• Buy Generic Retrovir
• Purchase Nevirapine Online
No hay comentarios:
Publicar un comentario