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Clinical Trials

Invega (paliperidone)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Approval Status:

Approved December 2006

Specific Treatments:


Therapeutic Areas

General Information

Invega is an oral extended-release (ER) major active metabolite of risperidone. It is an antagonist and thus interferes with neurotransmitter communication in the brain. It blocks dopamine type 2, serotonin type 2, and alpha 2 adrenergic receptors, all of which have been implicated in schizophrenia.

Invega is specifically indicated for the treatment of schizophrenia.

Invega is supplied as an extended release tablet available in 3 mg, 6 mg and 9 mg strengths, designed for oral administration. The recommended initial dose of the drug is 6 mg once daily, administered in the morning. The drug was observed to have dose-dependent efficacy, however this related to dose-dependent increases in adverse events. Dose increases above 6 mg/day should be made only after clinical reassessment. The maximum recommended dose is 12 mg/day.

Clinical Results

FDA Approval
FDA approval of Invega was based on the results of three clinical trials. These placebo-controlled, active-controlled (olanzapine), fixed-dose trials enrolled 1,665 non-elderly adult subjects who met DSM-IV criteria for schizophrenia, internationally. Subjects received placebo or Invega at 3, 6, 9, 12, and 15 mg/day for six weeks. Efficacy was evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Personal and Social Performance (PSP) scale. Results revealed all doses of Invega to be superior to placebo on both the PANSS and PSP scales. The mean effects at all doses were fairly similar, although the higher doses in all studies were numerically superior.

Ongoing Study Commitments

  • Janssen has agreed to repeat the study in postmarketing using doses that include a maximally tolerated dose for the dams, as the original pre- and postnatal developmental study in rats did not use high enough doses to adequately evaluate the effects of paliperidone on this phase of reproduction.
    Protocol Submission: January 2007
    Study Start: July 2007
    Final Report Submission: December 2008
  • Janssen has agreed to conduct a study to better explore for a minimal effective dose being that in the one study that included a 3 mg dose of paliperidone ER, the dose was shown to be about as effective as higher doses. The FDA therefore believes that Janssen has not fully evaluated the lower end of the dose response curve.
    Protocol Submission: April 2007
    Study Start: November 2007
    Final Report Submission: January 2011
  • Janssen has agreed to submit deferred pediatric studies under PREA for the treatment of adolescent schizophrenia ages 12 to 17 years, and to develop other information, e.g., pharmacokinetic, pertinent to using the drug in the pediatric population.
    Final Report Submission: December 2009

Side Effects

Adverse events associated with the use of Invega may include, but are not limited to, the following:

  • Parkinsonism
  • Akathisia
  • Dyskinesia
  • Tachycardia
  • Headache
  • Somnolence
  • Anxiety
  • Hyperkinesia
  • Extrapyramidal disorder
  • Dystonia

In addition, Invega was shown to induce orthostatic hypotension and syncope in some patients because of its alpha-blocking activity. Thus, it should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions that predispose the patient to hypotension.

Mechanism of Action

Invega uses osmotic pressure to deliver paliperidone at a controlled rate. It is an oral extended-release (ER) major active metabolite of risperidone. Although the exact mechanism of action is unknown, it is thought that Invega acts as an antagonist and thus interferes with neurotransmitter communication in the brain. It blocks dopamine type 2, serotonin type 2, and alpha 2 adrenergic receptors, all of which have been implicated in schizophrenia.

Literature References

Kramer M, Simpson G, Maciulis V, Kushner S, Vijapurkar U, Lim P, Eerdekens M Paliperidone Extended-Release Tablets for Prevention of Symptom Recurrence in Patients With Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study. Journal of clinical psychopharmacology 2007 Feb;27(1):6-14.

Kane J, Canas F, Kramer M, Ford L, Gassmann-Mayer C, Lim P, Eerdekens M Treatment of schizophrenia with paliperidone extended-release tablets: A 6-week placebo-controlled trial. Schizophrenia research 2006 Nov 7.

Zhu HJ, Wang JS, Markowitz JS, Donovan JL, Gibson BB, Devane CL Risperidone and Paliperidone Inhibit P-Glycoprotein Activity In Vitro. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2006 Aug 23.

Riedel M, Schwarz MJ, Strassnig M, Spellmann I, Muller-Arends A, Weber K, Zach J, Muller N, Moller HJ Risperidone plasma levels, clinical response and side-effects. European archives of psychiatry and clinical neuroscience 2005 Aug;255(4):261-8. Epub 2004 Nov 29.

Verma SK, Tan CH, Chan YH, Chong SA Plasma risperidone levels and clinical response in patients with first-episode psychosis. Journal of clinical psychopharmacology 2005 Dec;25(6):609-11.

Spina E, Avenoso A, Facciola G, Salemi M, Scordo MG, Ancione M, Madia AG, Perucca E Relationship between plasma risperidone and 9-hydroxyrisperidone concentrations and clinical response in patients with schizophrenia. Psychopharmacology 2001 Jan 1;153(2):238-43.

Additional Information

For additional information regarding Invega or schizophrenia, please visit the Invega web page.

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