INVEGA™ Shows Favorable Long Term Safety Profile In A One Year Study Of Patients With Schizophrenia

(December 27, 2007) -- INVEGA™ (paliperidone) Extended-Release Tablets showed favorable long-term safety and tolerability during a one-year open-label extension (OLE) study, according to a new, company-sponsored study. In addition, patient symptom scores improved or were stable, on average, over this 52-week study1.

The study was designed to evaluate the long-term safety of INVEGA™, an oral, atypical anti-psychotic approved for the treatment of schizophrenia. Discontinuations due to treatment-emergent adverse events (TEAEs) and the total number of serious TEAEs were both six percent. Other assessments such as cardiovascular, metabolic and weight-related assessments showed either no mean change or clinically minimal change as a result of the treatment. Symptoms of schizophrenia were reduced during long-term open-label treatment in those patients that transitioned from placebo to INVEGA™ and were maintained in those that were previously on INVEGA™ as assessed by the Positive and Negative Symptoms of Schizophrenia (PANSSa) scores.

"This long-term extension trial adds to the body of knowledge regarding the safety of INVEGA™ in the longer-term treatment of schizophrenia. The study also suggests that symptom control is maintained over time," said George M. Simpson, MD, Professor of Research, Director Outpatient Clinic, Keck School of Medicine of the University of Southern California. Dr. Simpson is a principal investigator of the study and a consultant to its sponsors Ortho-McNeil Janssen Scientific Affairs, LLC, Johnson & Johnson Pharmaceutical Research & Development, LLC, and Janssen, L.P., the company that markets INVEGA™.

The study consisted of 235 patients (154 male; 81 female) who had participated in the prior double-blind (DB) recurrence prevention study. This study demonstrated a significantly longer time to relapse in patients treated with INVEGA™ compared with those who received placebo and had been brought to an early completion when efficacy was established at its interim analysis. Of the 235 patients, 72 received INVEGA™, 80 received placebo, and 83 were enrolled directly into the OLE due to the early completion of the DB phase. These 83 patients had received INVEGA™ for a variable period of time prior to their entry into the OLE (sometime during the initial 14-week combined run-in and stabilization period).

Patients were 18-65 years old and met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria of schizophrenia for at least one year). The mean age of patients who entered was 35.8 years old.

Treatment in the OLE phase was initiated at a dose of 9 mg/day with changes in dose increments of 3 mg/day, to a maximum of 15 mg/day or minimum of 3 mg/day permitted.

Sixty percent of patients completed the OLE. TEAEs occurred in 69 percent of patients. The discontinuation rate due to adverse effects was six percent (n=12). TEAEs that occurred with an incidence of eight percent or more were tremor (13 percent; n=31), akathisia (11 percent; n=25), headache (eight percent; n=19), and insomnia (eight percent; n=18).

Safety for INVEGA™ was evaluated from OLE baseline to end point, in the context of a systematic review of TEAEs, clinical laboratory tests, body weight and body mass index, electrocardiograms and EPS incidence using the Simpson Angus Rating Scale, Barnes Akathisia Rating Scale and Abnormal Involuntary Movement Scale. Efficacy was evaluated as a secondary endpoint using the total PANSS score, with a negative score indicating a worsening of symptoms.

The mean changes observed in the total PANSS were:

-15.7±20.09 for patients who had been treated with placebo during DB, and who were then started on INVEGA™ during the OLE:

-6.3±18.91 for those initially assigned to INVEGA™ during DB, and then continued on INVEGA™ during the OLE; and

-3.9±13.85 for those 83 patients who had previously received up to 14 weeks of INVEGA™ while enrolled in the "run-in/stabilization phase" of the initial DB study (i.e. were never eligible for randomization to placebo), and who entered into the OLE directly.

Ortho-McNeil Janssen Scientific Affairs, LLC and Johnson & Johnson Pharmaceutical Research & Development, LLC sponsored this clinical study. Janssen, L.P, markets INVEGA™ in the U.S. Each of these companies is a subsidiary of Johnson & Johnson. Additional details about the study are available upon request.

For more information about Janssen, L.P., visit http://www.janssen.com.

Worldwide, it is estimated that one person in every 100 develops schizophrenia, one of the most serious types of mental illness. In the United States, there are currently two million people with schizophrenia, with men and women affected equally. The disease is marked by positive symptoms (hallucinations and delusions) and negative symptoms (depression, blunted emotions, and social withdrawal), as well as by disorganized thinking.

INVEGA™, an atypical antipsychotic medication, was first approved in the U.S. in December 2006. It is approved for the acute and maintenance treatment of schizophrenia in the U.S. and for the treatment of schizophrenia in the E.U.

Important Safety Information For INVEGA™

INVEGA™ (paliperidone) extended-release tablets is indicated for the acute and maintenance treatment of schizophrenia.

Elderly Patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. . INVEGA™ (paliperidone) is not approved for the treatment of patients with dementia-related psychosis.

The most common side effects that occurred with INVEGA™ were restlessness and extrapyramidal disorder (for example: involuntary movements, tremors and muscle stiffness). One risk of INVEGA™ is that it may change your heart rhythm. This effect is potentially serious, and you should talk to your doctor about any current or past heart problems. Some medications interact with INVEGA™. Please inform your health care professional of any medications or supplements that you are taking.

Neuroleptic Malignant Syndrome (NMS) is a rare and potentially fatal side effect reported with INVEGA™ and similar medicines. Call your doctor immediately if the person being treated develops symptoms such as high fever; stiff muscles; shaking; confusion; sweating; changes in pulse, heart rate, or blood pressure; or muscle pain and weakness. Treatment should be stopped if the person being treated has NMS.

Tardive Dyskinesia (TD) is a serious, sometimes permanent side effect reported with INVEGA™ and similar medications. TD includes uncontrollable movements of the face, tongue, and other parts of the 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 overall dose taken by the patient. This condition can develop after a brief period of therapy at low doses, although this is much less common. There is no known treatment for TD, but it may go away partially or completely if therapy is stopped.

INVEGA™ 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.

INVEGA™ and similar medications can raise the blood levels of a hormone known as prolactin, causing a condition known as hyperprolactinemia. Blood levels of prolactin remain elevated with continued use. Some side effects seen with these medications include the absence of a menstrual period; breasts producing milk; the development of breasts by males; and the inability to achieve an erection. The connection between prolactin levels and side effects is unknown.

High blood sugar and diabetes have been reported with INVEGA™ and similar medications. If the person being treated has diabetes or risk factors such as being overweight or a family history of diabetes, blood sugar testing should be performed at the beginning and throughout treatment with INVEGA™. Complications of diabetes can be serious and even life threatening. If signs of high blood sugar or diabetes develop, such as being thirsty all the time, going to the bathroom a lot, or feeling weak or hungry, contact your doctor.

People with narrowing or blockage of the gastrointestinal tract (esophagus, stomach or small or large intestine) should talk to their health care professional before taking INVEGA™.

Some people taking INVEGA™ may feel faint or lightheaded when they stand up or sit up too quickly. By standing up or sitting up slowly and following your health care professional's dosing instructions, this side effect may be reduced or it may go away over time.

Extrapyramidal Symptoms (EPS) are usually persistent movement disorders or muscle disturbances, such as restlessness, tremors, and muscle stiffness. If you observe any of these symptoms, talk to your health care professional.

Inform your health care professional if you are pregnant or if you are planning to get pregnant while taking INVEGA™. Do not breast-feed if you are taking INVEGA™.

INVEGA™ may affect your driving ability; therefore, do not drive or operate machines before talking to your health care professional. Avoid alcohol while on INVEGA™.

INVEGA™ may affect alertness and motor skills; use caution until the effect of INVEGA™ is known.

INVEGA™ may make you more sensitive to heat. You may have trouble cooling off, or be more likely to become dehydrated, so take care when exercising or when doing things that make you warm. INVEGA™ should be swallowed whole. Tablets should not be chewed, divided, or crushed. Do not be worried if you see something that looks like a tablet in your stool. This is what is left of the tablet after all the medicine has been released.

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Janssen, L.P., based in Titusville, NJ, is the only pharmaceutical company in the U.S. dedicated solely to mental health. The company currently markets prescription medications for the treatment of schizophrenia, bipolar mania, and irritability associated with autistic disorder. For more information about Janssen, L.P., visit http://www.janssen.com.

1 Kramer M, Simpson G, Kushner S et al., Long-term safety/tolerability of paliperidone extended-release tablets: 52-week, open-label, extension phase of a schizophrenia symptom recurrence prevention study, December 2007

aPositive and Negative Symptoms of Schizophrenia (PANSS) is a standard rating scale used in trials to assess the severity of symptoms. The scale consists of 30 items, which are assessed from absent to extreme, and these are divided into both positive and negative symptoms

Source: Medical News Today

Last updated: 12/07

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