Phase III Study Demonstrates INVEGA® SUSTENNA™ (paliperidone palmitate) Statistically Similar to
RISPERDAL®CONSTA® (risperidone) Long-Acting Injection
Titusville, N.J., December 10, 2009 —
Treatment with once-monthly INVEGA® SUSTENNA™ is not inferior to
treatment with bi-weekly RISPERDAL®CONSTA®, according to new data
from a comparative study of both treatments in patients with
schizophrenia. Results of the 13-week clinical trial were released
this week.
An estimated one percent of the world's population suffers from
schizophrenia - a brain disorder that impairs a person's ability to
think clearly, relate to others, and distinguish between reality
and imagination. In the U.S., approximately 2.4 million Americans
have schizophrenia, with men and women affected equally.1
Non-adherence to medication treatment is a common problem
encountered in patients with schizophrenia, which can lead to
relapse (an increase in symptoms) and hospitalization.2 Since both
INVEGA SUSTENNA and RISPERDAL CONSTA are given by a healthcare
professional, it offers the physician a way to monitor patient
medication adherence and intervene when a patient misses a dose.
Both products offer flexibility to physicians and patients, based
on their dosing regimens, thereby offering an important option to
those who may need it.
The objective of this study was to show that INVEGA SUSTENNA was
statistically similar (non-inferior) to RISPERDAL CONSTA, as
measured by the Positive and Negative Syndrome Scale (PANSS).
INVEGA SUSTENNA, a once-monthly injectable atypical antipsychotic,
was recently approved in the U.S. for the acute and maintenance
treatment of schizophrenia in adults. RISPERDAL CONSTA, the first
long-acting injectable atypical antipsychotic, was approved for the
treatment of schizophrenia in adults in the U.S. in 2003, and
recently was approved for use as maintenance therapy in the
treatment of Bipolar I Disorder.
"Physicians need treatment options that match the needs of their
patients, particularly when compliance is a significant issue.
INVEGA SUSTENNA was non-inferior to RISPERDAL CONSTA in the
treatment of schizophrenia in this trial, which validates that
these are both good options," said George Simpson, M.D., professor
of research at Keck School of Medicine, University of Southern
California and clinical investigator for the INVEGA SUSTENNA
program. "The differences between the two products, such as the
shorter or longer dosing interval or the need for oral
supplementation, provide options for physicians to decide what will
work best for an individual patient."
About the Study
The 13-week, randomized, double-blind, double-dummy trial included
1220 adults with a diagnosis of schizophrenia and a PANSS total
score of 60 to 120. Participants were randomly assigned to receive
INVEGA SUSTENNA (IS) plus oral placebo or RISPERDAL CONSTA (RC)
plus oral risperidone for the first three weeks.
Patients assigned to IS received an initiation dosing regimen of
234* mg on day 1 and 156 mg on day 8, followed by once-monthly
dosing on day 36 (78 mg or 156 mg) and day 64 (78 mg, 156 mg, or
234 mg). Additional placebo injections were administered to match
RC dosing. Patients assigned to RC received their first injection
on day 8, followed by biweekly injections on day 22, 36, 50, 64 and
78. This was supplemented with placebo injections to match IS
dosing. The 25 mg starting dose of RC could have been increased up
to 37.5 mg starting on day 36 and up to 50 mg on day 64. Patients
on RC received mandatory oral risperidone supplementation from days
1 to 28. Oral supplementation was optional with subsequent dose
increases.
The primary endpoint of the trial was the change in the PANSS total
score versus baseline. Non-inferiority would be concluded by
calculation using a 95% confidence interval (CI) based on a
pre-specified change in total PANSS score. Secondary efficacy
measures included change from baseline for Clinical Global
Impression-Severity (CGI-S) and Personal and Social Performance
(PSP) Scale.
Results showed similar improvement in the mean change from baseline
to endpoint in PANSS total score for IS (-18.6) and RC groups
(-17.9). Because the lower limit of the 95% CI exceeded the
pre-specified margin of -5, IS was concluded to be non-inferior to
RC. Patients' severity of illness (CGI-S) and personal and social
performance (PSP) improved similarly in both groups.
The overall incidence of treatment-emergent adverse events (TEAEs)
were comparable in the IS group (57.9%) and in the RC group
(52.8%). TEAEs that occurred in more than 5% in both treatment
groups were: insomnia, headache, somnolence, and injection-site
pain. The incidence of extrapyramidal symptom-related TEAEs was
similar for both treatment groups. The mean increases in body
weight at endpoint also were similar between treatment groups (IS:
1.1 [3.36] kg; RC: 1.0 [3.14] kg).
The study was sponsored by Johnson & Johnson Pharmaceutical
Research and Development, L.L.C. (J&JPRD). In the U.S., Janssen®,
Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. markets
INVEGA® SUSTENNA™ and RISPERDAL® CONSTA®. Visit www.invegasustenna.com
and www.risperdalconsta.com for full prescribing information.
INVEGA® SUSTENNA™ was approved in July 2009 in the U.S. for the acute
and maintenance treatment of schizophrenia in adults and utilizes
the NanoCrystal® Technology, which is a proprietary technology
developed by Elan Drug Technologies through Elan Pharma
International Limited and other Elan affiliates.
RISPERDAL CONSTA was approved in 2003 for the treatment of
schizophrenia and was approved in May 2009 for monotherapy and
adjunctive therapy in the maintenance treatment of Bipolar I
Disorder in adults.
IMPORTANT SAFETY INFORMATION FOR INVEGA® SUSTENNA™
INVEGA® SUSTENNA™ is not approved for the treatment of
dementia-related psychosis in elderly patients. Elderly patients
who were given oral antipsychotics like INVEGA® SUSTENNA™ in
clinical studies for psychosis caused by dementia (memory problems)
had a higher risk of death.
Neuroleptic Malignant Syndrome (NMS) is a rare, but serious side
effect that could be fatal and has been reported with INVEGA® SUSTENNA™ and similar medicines. Call the doctor right away if you
develop symptoms such as a high fever, rigid muscles, shaking,
confusion, sweating more than usual, increased heart rate or blood
pressure, or muscle pain or weakness. Treatment should be stopped
if you are being treated for NMS.
Tardive Dyskinesia (TD) is a rare, but serious and sometimes
permanent side effect reported with INVEGA® SUSTENNA™ and similar
medicines. Call your doctor right away if you start to develop
twitching or jerking movements that you cannot control in your
face, tongue, or other parts of your body. The risk of developing
TD and the chance that it will become permanent is thought to
increase with the length of therapy and the total dose received.
This condition can also develop after a short period of treatment
at low doses but this is less common. There is no known treatment
for TD but it may go away partially or completely if the medicine
is stopped.
One risk of INVEGA® SUSTENNA™ is that it may change your heart
rhythm. This effect is potentially serious. You should talk to your
doctor about any current or past heart problems. Because these
problems could mean you're having a heart rhythm abnormality,
contact your doctor IMMEDIATELY if you feel faint or feel a change
in the way that your heart beats (palpitations).
High blood sugar and diabetes have been reported with INVEGA® SUSTENNA™ and similar medicines. If you already have diabetes or
have risk factors such as being overweight or a family history of
diabetes, blood sugar testing should be done at the beginning and
during the treatment. The complications of diabetes can be serious
and even life-threatening. Call your doctor if you develop signs of
high blood sugar or diabetes, such as being thirsty all the time,
having to urinate or "pass urine" more often than usual, or feeling
weak or hungry.
Weight gain has been observed with INVEGA® SUSTENNA™ and other
atypical antipsychotic medications. If you notice that you are
gaining weight, please notify your doctor.
Some people may feel faint, dizzy, or may pass out when they stand
up or sit up suddenly. Be careful not to get up too quickly. It may
help if you get up slowly and sit on the edge of the bed or chair
for a few minutes before you stand up. These symptoms may decrease
or go away after your body becomes used to the medicine.
INVEGA® SUSTENNA™ and similar medicines have been associated with
decreases in the counts of white cells in circulating blood. If you
have a history of low white blood cell counts or have unexplained
fever or infection, then please contact your doctor right away.
INVEGA® SUSTENNA™ and similar medicines can raise the blood levels
of a hormone called prolactin and blood levels of prolactin remain
high with continued use. This may result in some side effects
including missed menstrual periods, leakage of milk from the
breasts, development of breasts in men, or problems with erection.
If you have a prolonged or painful erection lasting more than 4
hours, seek immediate medical help to avoid long-term injury. Call
your doctor right away if you start thinking about suicide or
wanting to hurt yourself.
INVEGA® SUSTENNA™ can make some people feel dizzy, sleepy, or less
alert. Until you know how you are going to respond to INVEGA® SUSTENNA™, be careful driving a car, operating machines, or doing
things that require you to be alert.
This medicine may make you more sensitive to heat. You may have
trouble cooling off or be more likely to become dehydrated. Be
careful when you exercise or spend time doing things that make you
warm.
Some medications interact with INVEGA® SUSTENNA™. Please inform
your healthcare professional of any medications or supplements that
you are taking. INVEGA® SUSTENNA™ should be used cautiously in
people with a seizure disorder, who have had seizures in the past,
or who have conditions that increase their risk for seizures.
Inform your healthcare professional if you become pregnant or
intend to become pregnant during therapy with INVEGA® SUSTENNA™.
Do not drink alcohol while you are taking INVEGA® SUSTENNA™.
In a study of people taking INVEGA® SUSTENNA™, common side effects
in the treatment of schizophrenia were reactions at the injection
site, sleepiness, dizziness, feeling of inner restlessness, and
abnormal muscle movements, including tremor (shaking), shuffling,
uncontrolled involuntary movements, and abnormal movements of the
eyes.
This is not a complete list of all possible side effects. Ask your
doctor or treatment team if you have any questions or want more
information.
If you have any questions about INVEGA® SUSTENNA™ or your therapy,
talk with your doctor.
IMPORTANT SAFETY INFORMATION FOR RISPERDAL®CONSTA®
Elderly Patients with dementia-related psychosis treated with
antipsychotic drugs are at an increased risk of death compared to
placebo. RISPERDAL®CONSTA® (risperidone) is not approved for the
treatment of patients with dementia-related psychosis.
Cerebrovascular Adverse Events (CAEs): CAEs, including fatalities,
have been reported in elderly patients with dementia-related
psychosis taking oral risperidone in clinical trials. The incidence
of CAEs with risperidone was significantly higher than with
placebo. RISPERDAL®CONSTA® is not approved for the treatment of
patients with dementia-related psychosis.
Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal
symptom complex, has been reported with the use of antipsychotic
medications, including RISPERDAL®CONSTA®. Clinical manifestations
include muscle rigidity, fever, altered mental status and evidence
of autonomic instability (see full Prescribing Information).
Management should include immediate discontinuation of
antipsychotic drugs and other drugs not essential to concurrent
therapy, intensive symptomatic treatment and medical monitoring,
and treatment of any concomitant serious medical problems.
Tardive Dyskinesia (TD): TD is a syndrome of potentially
irreversible, involuntary, dyskinetic movements that may develop in
patients treated with antipsychotic medications. The risk of
developing TD and the likelihood that dyskinetic movements will
become irreversible are believed to increase with duration of
treatment and total cumulative dose. Elderly patients appeared to
be at increased risk for TD. Prescribing should be consistent with
the need to minimize the risk of TD. The syndrome may remit,
partially or completely, if antipsychotic treatment is withdrawn.
Hyperglycemia and Diabetes: Hyperglycemia, some cases extreme and
associated with ketoacidosis, hyperosmolar coma or death has been
reported in patients treated with atypical antipsychotics (APS),
including RISPERDAL®CONSTA®. Patients starting treatment with APS
who have or are at risk for diabetes should undergo fasting blood
glucose testing at the beginning of and during treatment. Patients
who develop symptoms of hyperglycemia should also undergo fasting
blood glucose testing.
Hyperprolactinemia: As with other drugs that antagonize dopamine D2
receptors,
RISPERDAL®CONSTA® elevates prolactin levels and the elevation
persists during chronic administration. Risperidone is associated
with higher levels of prolactin elevation than other antipsychotic
agents.
Orthostatic Hypotension: RISPERDAL®CONSTA® may induce orthostatic
hypotension associated with dizziness, tachycardia, and in some
patients, syncope, especially during the initial dose-titration
period. Monitoring should be considered in patients for whom this
may be of concern. RISPERDAL®CONSTA® should be used with caution
in patients with known cardiovascular disease, and conditions that
would predispose patients to hypotension.
Leukopenia, Neutropenia and Agranulocytosis have been reported with
antipsychotics, including risperidone. Patients with a pre-existing
low white blood cell count (WBC) or a history of
leukopenia/neutropenia should have frequent complete blood cell
counts during the first few months of therapy. At the first sign of
a decline in WBC and in the absence of other causative factors,
discontinuation of RISPERDAL®CONSTA® should be considered.
Potential for Cognitive and Motor Impairment: RISPERDAL®CONSTA®
has the potential to impair judgment, thinking, or motor skills.
Patients should be cautioned about operating hazardous machinery,
including motor vehicles, until they are reasonably certain that
RISPERDAL®CONSTA® does not affect them adversely.
Seizures: RISPERDAL®CONSTA® should be used cautiously in patients
with a history of seizures or with conditions that potentially
lower seizure threshold.
Dysphagia: Esophageal dysmotility and aspiration can occur. Use
cautiously in patients at risk for aspiration pneumonia.
Priapism has been reported. Severe priapism may require surgical
intervention.
Thrombotic Thrombocytopenic Purpura (TTP) has been reported.
Administration: RISPERDAL®CONSTA® should be injected into the
deltoid or gluteal muscle, and care must be taken to avoid
inadvertent injection into a blood vessel.
Suicide: The possibility of suicide attempt is inherent in
schizophrenia or bipolar disorder. Close supervision of high-risk
patients should accompany drug therapy.
Increased sensitivity in patients with Parkinson's disease or those
with dementia with Lewy bodies has been reported. Manifestations
and features are consistent with NMS.
Use RISPERDAL®CONSTA® with caution in patients with conditions and
medical conditions that could affect metabolism or hemodynamic
responses (e.g. recent myocardial infarction or unstable cardiac
disease).
Maintenance Treatment: Patients should be periodically reassessed
to determine the need for continued treatment.
Commonly Observed Adverse Reactions for RISPERDAL®CONSTA®: The
most common adverse reactions in clinical trials in patients with
schizophrenia (≥5%) were headache, Parkinsonism, dizziness,
akathisia, fatigue, constipation, dyspepsia, sedation, weight
increase, pain in extremities, and dry mouth.
The most common adverse reactions in clinical trials in patients
with bipolar disorder were weight increased (5% in monotherapy
trial) and tremor and Parkinsonism (> 10% in adjunctive therapy
trial).
If you have any questions about RISPERDAL®CONSTA® or your therapy,
talk with your doctor.
About Johnson & Johnson Pharmaceutical Research & Development,
L.L.C.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
(J&JPRD) is headquartered in Raritan, New Jersey (USA), and has
nine sites throughout Europe and the United States. J&JPRD employs
approximately 3,500 people and is leveraging drug discovery, drug
evaluation and drug development in a variety of therapeutic areas
to address unmet medical needs worldwide. The company's major
therapeutic areas of focus include hematology, oncology, infectious
disease, obesity and metabolic disorders, neurology and psychiatry,
pain and women's health.
About Janssen
Janssen®, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.,
is based in Titusville, N.J., and is the only large pharmaceutical
company in the U.S. dedicated solely to mental health. It currently
has prescription medications for the treatment of schizophrenia,
bipolar mania, and the treatment of symptoms associated with
autistic disorders. Ortho-McNeil-Janssen Pharmaceuticals, Inc. is a
member of the Johnson & Johnson family of companies. For more
information about Janssen, visit www.janssen.com.
References
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