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Currently Enrolling Trials

General Information

Fanapt is a psychotropic agent belonging to the chemical class of piperidinyl-benzisoxazole derivatives. The mechanism of action of Fanapt is unknown. However it is proposed that the efficacy of Fanapt is mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5-HT2) antagonisms.

Fanapt is specifically indicated for the acute treatment of adults with schizophrenia. Fanapt is supplied as a tablet designed for oral administration. Fanapt must be titrated slowly from a low starting dose to avoid orthostatic hypotension.

Usual Dose

The recommended starting dose for Fanapt tablets is 1 mg twice daily. Increases to reach the target dose range of 6-12 mg twice daily may be made with daily dosage adjustments to 2 mg twice daily, 4 mg twice daily, 6 mg twice daily, 8 mg twice daily, 10 mg twice daily, and 12 mg twice daily on days 2, 3, 4, 5, 6, and 7, respectively. The maximum recommended dose is 12 mg twice daily (24 mg/day).

Dosing in Special Populations

Dosage adjustment for patients taking Fanapt concomitantly with potential CYP2D6 and CYP3A4 inhibitors: Fanapt dose should be reduced by one-half when administered concomitantly with strong CYP2D6 and CYP3A4 inhibitors. When the CYP2D6 or CYP3A4 inhibitor is withdrawn from the combination therapy, Fanapt dose should then be increased to where it was before. Maintenance Treatment There is no body of evidence available to answer how long the patient treated with Fanapt should be maintained, however it is generally recommended that responding patients be continued beyond the acute response. Patients should be periodically reassessed. Reinitiation of Treatment in Patients Previously Discontinued No data to specifically addresses re-initiation of treatment, however it is recommended that the initiation titration schedule be followed whenever patients have had an interval off Fanapt of more than 3 days. Switching From Other Antipsychotics No specific data addresses how patients with schizophrenia can be switched from other antipsychotics to Fanapt or how Fanapt can be used concomitantly with other antipsychotics. Although immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized.

Clinical Results

FDA Approval
FDA approval of Fanapt was based on the results of two clinical studies.

Six-Week Study
This placebo-controlled trial enrolled 706 subjects who met the DSM-III/IV criteria for schizophrenia. The subjects received two dose ranges of Fanapt (12-16 mg/day or 20-24 mg/day) compared to placebo and an active control. Fanapt was titrated starting 1 mg twice daily on day 1 and increasing to 2, 4, 6, 8, 10 and 12 mg twice daily on days 2, 3, 4, 5, 6, and 7, as needed. The primary endpoint was change from baseline on the Brief Psychiatric Rating Scale (BPRS) total score at the end of treatment (Day 42). Both the 12-16 mg/day and the 20-24 mg/day dose ranges of Fanapt were superior to placebo on the BPRS total score. The active control antipsychotic drug appeared to be superior to Fanapt in this trial within the first 2 weeks, a finding that may in part be explained by the more rapid titration that was possible for that drug.

Four-Week Study
This placebo-controlled trial enrolled 604 subjects who met the DSM-III/IV criteria for schizophrenia. The subjects one fixed dose of Fanapt (24 mg/day) compared to placebo and an active control. Fanapt was titrated starting 1 mg twice daily on day 1 and increasing to 2, 4, 6, 8, 10 and 12 mg twice daily on days 2, 3, 4, 5, 6, and 7. The primary endpoint was change from baseline on the Positive and Negative Syndrome Scale (PANSS) total score at the end of treatment (Day 28). The 24 mg/day Fanapt dose was superior to placebo in the PANSS total score. Fanapt appeared to have similar efficacy to the active control drug which also needed a slow titration to the target dose.

Ongoing Study Commitments

Vanda has agreed to a deferred pediatric study under PREA for the treatment of schizophrenia in pediatric patients ages 13 to 17. A study to obtain pharmacokinetic data and provide information pertinent to dosing of iloperidone tablets in the relevant pediatric population.
Final Protocol Submission: by March 1, 2010
Study Completion Date: by September 1, 2013
Final Report Submission: by March 1, 2014
Vanda has agreed to a deferred pediatric study under PREA for the treatment of schizophrenia in pediatric patients ages 13 to 17. A study of the efficacy and safety of iloperidone tablets in the relevant pediatric population.
Final Protocol Submission: by March 1, 2010
Study Completion Date: by September 1, 2013
Final Report Submission: by March 1, 2014
Vanda has agreed to Complete the ongoing P95 carcinogenicity study.
Study Completion Date: by February 28, 2010
Final Report Submission: by May 31, 2010
Vanda has agreed to Conduct a study investigating the possible in vitro interaction of iloperidone and P- Glycoprotein (P-Gp).
Final Protocol Submission: by August 1, 2009
Study Completion Date: by October 1, 2009
Final Report Submission: by November 1, 2009
Vanda has agreed to repeat their clinical trial CIL0522A0103, conducted with a group of subjects with mildly and moderately impaired hepatic function, comparing them to normals in the same trial.
Final Protocol Submission: by November 1, 2009
Trial Completion Date: by November 1, 2010
Final Report Submission: by May 1, 2011
Vanda has agreed to a long-term randomized withdrawal clinical trial to address longer-term efficacy for the drug at appropriate doses.
Protocol Submission: by November 1, 2009
Trial Completion Date: by November 1, 2012
Final Report Submission: by May 1, 2013

Side Effects

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

Dizziness
Somnolence
Dry Mouth
Nausea
Tachycardia
Diarrhea
Orthostatic Hypotension
Weight Gain

Mechanism of Action

Literature References

Potkin SG, Litman RE, Torres R, Wolfgang CD Efficacy of iloperidone in the treatment of schizophrenia: initial phase 3 studies. Journal of Clinical Psycopharmacology 2008 Apr;28(2 Suppl 1):S4-11

Kane JM, Lauriello J, Laska E, Di Marino M, Wolfgang CD Long-term efficacy and safety of iloperidone: results from 3 clinical trials for the treatment of schizophrenia. Journal of Clinical Psycopharmacology 2008 Apr;28(2 Suppl 1):S29-35

Cutler AJ, Kalali AH, Weiden PJ, Hamilton J, Wolfgang CD Four-week, double-blind, placebo- and ziprasidone-controlled trial of iloperidone in patients with acute exacerbations of schizophrenia. Journal of Clinical Psycopharmacology 2008 Apr;28(2 Suppl 1):S20-8

Weiden PJ, Cutler AJ, Polymeropoulos MH, Wolfgang CD Safety profile of iloperidone: a pooled analysis of 6-week acute-phase pivotal trials. Journal of Clinical Psycopharmacology 2008 Apr;28(2 Suppl 1):S12-9

Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A Iloperidone binding to human and rat dopamine and 5-HT receptors. European Journal of Pharmacology 1996 Dec 19;317(2-3):417-23

Szczepanik AM, Brougham LR, Roehr JE, Conway PG, Ellis DB, Wilmot CA Ex vivo studies with iloperidone (HP 873), a potential atypical antipsychotic with dopamine D2/5-hydroxytryptamine2 receptor antagonist activity. The Journal of Pharmacology and Experimental Therapeutics 1996 Aug;278(2):913-20.

Sainati SM, Hubbard JW, Chi E, Grasing K, Brecher MB Safety, tolerability, and effect of food on the pharmacokinetics of iloperidone (HP 873), a potential atypical antipsychotic. Journal of Clinical Pharmacology 1995 Jul;35(7):713-20