Phase III Study Demonstrates INVEGA SUSTENNA) (paliperidone palmitate) Statistically Similar to RISPERDAL CONSTA (risperidone) Long-Acting Injection
TITUSVILLE, N.J., Dec. 10 /PRNewswire/ -- Treatment with
once-monthly INVEGA® SUSTENNA(TM) 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(TM)
INVEGA® SUSTENNA(TM) is not approved for the treatment of
dementia-related psychosis in elderly patients. Elderly patients
who were given oral antipsychotics like INVEGA® SUSTENNA(TM) 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(TM) 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(TM) 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(TM) 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(TM) 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(TM) 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(TM) 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(TM) 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(TM) can make some people feel dizzy,
sleepy, or less alert. Until you know how you are going to respond
to INVEGA® SUSTENNA(TM), 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(TM). Please
inform your healthcare professional of any medications or
supplements that you are taking. INVEGA® SUSTENNA(TM) 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(TM).
Do not drink alcohol while you are taking INVEGA®
SUSTENNA(TM).
In a study of people taking INVEGA® SUSTENNA(TM), 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(TM) 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 (greater than or equal to 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.
*Because doses of paliperidone palmitate can be expressed both
in terms of milligram equivalents (mg eq.) of the pharmacologically
active fraction of paliperidone and in milligrams of paliperidone
palmitate, the doses expressed as 50, 100 and 150 mg eq. equate to
78, 156 and 234 mg respectively, of paliperidone palmitate.
(1)National Institutes of Mental Health Web site: http://www.nimh.nih.gov/health/publications/the-numbers-count-mental-disorders
-in-america/index.shtml#Schizophrenia. Accessed November 12,
2009.
(2)Sun SX, Liu GG, Christensen DB, Fu AZ. Review and analysis of
hospitalization costs associated with antipsychotic nonadherence in
the treatment of schizophrenia in the United States. Curr Med Res
Opin. Oct. 2007; 23 (10): 2305-12.
Source: Janssen(R), Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.
CONTACT: Media, Srikant Ramaswami, Office: +1-609-730-2658,
Cell:
+1-609-647-8195, Sramaswa@its.jnj.com or
Investors, Louise Mehrotra,
+1-732-524-6491 or Lesley Fishman, +1-732-524-3922, both of Johnson
& Johnson
Web Site: http://www.janssen.com/
Posted: December 2009
