Janssen Investigational Treatment for Schizophrenia Shows Positive Efficacy,
Independent Data Monitoring Committee Recommends Halting Trial and Unblinding
Data Based on Treatment Efficacy
TITUSVILLE, N.J., March 20, 2014
TITUSVILLE, N.J., March 20, 2014 /PRNewswire/ --Janssen Research &
Development, LLC announced today that following an Independent Data Monitoring
Committee (IDMC) recommendation based on positive efficacy, it has halted
early a Phase 3 clinical study of paliperidone palmitate 3-month formulation,
an investigational treatment for symptoms of schizophrenia in adults.
"We are really excited about this news because a medication's ability to delay
time to relapse in schizophrenia has significant clinical and societal
implications," said Husseini K. Manji, MD, Global Head, Neuroscience, Janssen
Research & Development. "Being able to delay relapse can prove to be
beneficial clinically to patients, to their caregivers and to the community."
The international, randomized, multicenter, double-blind clinical trial
evaluated the efficacy of paliperidone palmitate 3-month formulation compared
with placebo in delaying time to first occurrence of relapse of symptoms of
schizophrenia. Study patients who were randomized to treatment were first
stabilized with INVEGA^® SUSTENNA^® (paliperidone palmitate one-month
formulation), an approved treatment for schizophrenia, prior to receiving the
investigational 3-month formulation.
The primary outcome measure of the study was the time to first relapse event
in the double-blind phase of the study. Time to relapse is defined as the time
between randomization to treatment in the double-blind phase and the first
documentation of a relapse. The study began in April 2012 and 509 patients
The planned interim analysis was conducted after 60 percent (42 events) of
projected relapses occurred. The primary analysis of this study will be based
on the interim results of the efficacy endpoint of time to first relapse.
Events experienced by study patients after the decision to stop the study
will be included in an additional analysis of the primary efficacy endpoint.
The study results will be presented at a future medical congress and will also
be submitted for publication in a peer-reviewed journal.
The recommendation to stop and unblind the clinical study at this interim
analysis was made by an independent data monitoring committee based on
pre-specified criteria, specifically, achieving a statistically significant
difference from placebo in delaying time to relapse based upon the interim
analysis after 42 relapse events have occurred.
Study investigators will have the opportunity to switch patients enrolled in
the study to standard of care treatment for schizophrenia.
Following a final analysis of the study and discussions with the U.S. Food and
Drug Administration (FDA), Janssen Research & Development, LLC plans to file a
New Drug Application with the U.S. FDA for paliperidone palmitate 3 month
formulation by the end of 2014.
INVEGA^® SUSTENNA^® and the paliperidone palmitate 3-month formulation utilize
Alkermes' proprietary NanoCrystal^® technology, which enables solubility of
poorly water-soluble compounds.
About Paliperidone Palmitate (INVEGA^® SUSTENNA^®)
INVEGA^®SUSTENNA^®(paliperidone palmitate) is indicated for the treatment of
schizophrenia in an injection administered once monthly after starting doses.
Efficacy was established in four short-term studies and one longer-term study
IMPORTANT SAFETY INFORMATION FOR INVEGA^®SUSTENNA^®(paliperidone palmitate)
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED
oElderly patients with dementia-related psychosis treated with
antipsychotic drugs are at an increased risk of death.
oINVEGA® SUSTENNA® is not approved for the treatment of patients with
oSee full Prescribing Information for Warnings and Precautions (5.1).
oContraindications: Paliperidone is contraindicated in patients with a
known hypersensitivity to either paliperidone, risperidone, or to any
components of the formulation.
oCerebrovascular Adverse Reactions: Cerebrovascular Adverse Reactions
(e.g., stroke, transient ischemic attacks), including fatalities, were
reported in placebo-controlled trials in elderly patients with
dementia-related psychosis taking oral risperidone, aripiprazole, and
olanzapine. The incidence of Cerebrovascular Adverse Reactions was
significantly higher than with placebo. INVEGA^®SUSTENNA^®is not
approved for the treatment of patients with dementia-related psychosis.
oNeuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom
complex, has been reported with the use of antipsychotic medications,
including paliperidone. 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 close medical
monitoring, and treatment of any concomitant serious medical problems.
oQT Prolongation: Paliperidone causes a modest increase in the corrected QT
(QTc) interval. Avoid the use of drugs that also increase QTc interval and
in patients with risk factors for prolonged QTc interval. Paliperidone
should also be avoided in patients with congenital long QT syndrome and in
patients with a history of cardiac arrhythmias. Certain circumstances may
increase the risk of the occurrence of torsades de pointes and/or sudden
death in association with the use of drugs that prolong the QTc interval.
oTardive 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, but can
develop after relatively brief treatment at low doses. Elderly female
patients appeared to be at increased risk for TD, although it is
impossible to predict which patients will develop the syndrome.
Prescribing should be consistent with the need to minimize the risk of TD
(see full Prescribing Information). Discontinue drug if clinically
appropriate. The syndrome may remit, partially or completely, if
antipsychotic treatment is withdrawn.
oMetabolic Changes: Atypical antipsychotic drugs have been associated with
metabolic changes that may increase cardiovascular/cerebrovascular risk.
These metabolic changes include hyperglycemia, dyslipidemia, and body
weight gain. While all of the drugs in the class have been shown to
produce some metabolic changes, each drug has its own specific risk
oHyperglycemia and Diabetes Mellitus: Hyperglycemia and diabetes
mellitus, in some cases extreme and associated with ketoacidosis,
hyperosmolar coma or death have been reported in patients treated
with all atypical antipsychotics (APS). Patients starting treatment
with APS who have or are at risk for diabetes mellitus should undergo
fasting blood glucose testing at the beginning of and during
treatment. Patients who develop symptoms of hyperglycemia during
treatment should also undergo fasting blood glucose testing. All
patients treated with atypical antipsychotics should be monitored for
symptoms of hyperglycemia. Some patients require continuation of
antidiabetic treatment despite discontinuation of the suspect drug.
oDyslipidemia: Undesirable alterations have been observed in patients
treated with atypical antipsychotics.
oWeight Gain: Weight gain has been observed with atypical
antipsychotic use. Clinical monitoring of weight is recommended.
oOrthostatic Hypotension and Syncope: INVEGA^®SUSTENNA^®may induce
orthostatic hypotension in some patients due to its alpha-blocking
activity. INVEGA^®SUSTENNA^®should be used with caution in patients with
known cardiovascular disease, cerebrovascular disease or conditions that
would predispose patients to hypotension (e.g., dehydration, hypovolemia,
treatment with antihypertensive medications). Monitoring should be
considered in patients for whom this may be of concern.
oLeukopenia, Neutropenia and Agranulocytosis have been reported with
antipsychotics, including paliperidone. Patients with a history of
clinically significant low white blood cell count (WBC) or drug-induced
leukopenia/neutropenia should have frequent complete blood cell counts
during the first few months of therapy. At the first sign of a clinically
significant decline in WBC, and in the absence of other causative factors,
discontinuation of INVEGA^®SUSTENNA^®should be considered. Patients with
clinically significant neutropenia should be carefully monitored for fever
or other symptoms or signs of infection and treated promptly if such
symptoms or signs occur. Patients with severe neutropenia (absolute
neutrophil count <1000/mm^3) should discontinue INVEGA^®SUSTENNA^®and
have their WBC followed until recovery.
oHyperprolactinemia: As with other drugs that antagonize dopamine D
receptors, INVEGA^®SUSTENNA^®elevates prolactin levels and the elevation
persists during chronic administration. Paliperidone has a
prolactin-elevating effect similar to risperidone, which is associated
with higher levels of prolactin elevation than other antipsychotic agents.
oPotential for Cognitive and Motor Impairment: Somnolence, sedation, and
dizziness were reported as adverse reactions in subjects treated with
INVEGA^®SUSTENNA^®. INVEGA^®SUSTENNA^®has the potential to impair
judgment, thinking, or motor skills. Patients should be cautioned about
performing activities that require mental alertness such as operating
hazardous machinery, including motor vehicles, until they are reasonably
certain that INVEGA^®SUSTENNA^®does not adversely affect them.
oSeizures: INVEGA^®SUSTENNA^®should be used cautiously in patients with a
history of seizures or with conditions that potentially lower seizure
threshold. Conditions that lower seizure threshold may be more prevalent
in patients 65 years or older.
oAdministration: For intramuscular injection only. Care should be taken to
avoid inadvertent injection into a blood vessel.
oDrug Interactions: Strong CYP3A4 inducers: It may be necessary to increase
the dose of INVEGA^®SUSTENNA^®when a CYP3A4 strong inducer
(e.g. carbamazepine, rifampin, St. John's wort) is added. It may be
necessary to decrease the dose when a CYP3A4 strong inducer is
oPregnancy/Nursing: Patients should be advised to notify their physician if
they become pregnant/intend to become pregnant or intend to nurse during
treatment with INVEGA^®SUSTENNA^®.
oCommonly Observed Adverse Reactions for INVEGA^®SUSTENNA^®: The most
common adverse reactions in clinical trials in patients with schizophrenia
(greater than or equal to 5% and twice placebo) were injection site
reactions, somnolence/sedation, dizziness, akathisia and extrapyramidal
Please see full Prescribing Information including Boxed Warning for INVEGA®
SUSTENNA® (paliperidone palmitate) available at
About Janssen Research & Development, LLC
Janssen Research & Development, LLC is headquartered in Raritan, N.J. and has
affiliated facilities in Europe, the United States and Asia. Janssen Research
& Development is leveraging a combination of internal and external innovation
to discover and develop novel medicines and solutions in five distinct
therapeutic areas: Neuroscience, Oncology, Immunology, Infectious Diseases and
Vaccines, and Cardiovascular and Metabolism. For more information about
Janssen Research & Development, LLC visit www.janssenrnd.com.
Janssen Research & Development is part of the Janssen Pharmaceutical Companies
of Johnson & Johnson. Driven by our commitment to patients, we work together
to bring innovative ideas, products, services and solutions to address serious
unmet medical needs around the world.
(This press release contains "forward-looking statements" as defined in the
Private Securities Litigation Reform Act of 1995 regarding products in
development. The reader is cautioned not to rely on these forward-looking
statements. These statements are based on current expectations of future
events. If underlying assumptions prove inaccurate or unknown risks or
uncertainties materialize, actual results could vary materially from the
expectations and projections of Janssen Research & Development, LLC and/or
Johnson & Johnson. Risks and uncertainties include, but are not limited to:
challenges inherent in new product development, including obtaining regulatory
approvals; competition, including technological advances, new products and
patents attained by competitors; challenges to patents; changes in behavior
and spending patterns or financial distress of purchasers of health care
products and services; changes to governmental laws and regulations and
domestic and foreign health care reforms; and general industry conditions
including trends toward health care cost containment. A further list and
description of these risks, uncertainties and other factors can be found in
Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended
December 29, 2013, including in Exhibit 99 thereto, and our subsequent filings
with the Securities and Exchange Commission. Copies of these filings are
available online at www.sec.gov, www.jnj.com or on request from Johnson &
Johnson. None of the Janssen Pharmaceutical Companies or Johnson & Johnson
undertakes to update any forward-looking statement as a result of new
information or future events or developments.)
SOURCE Janssen Research & Development, LLC
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