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Iloperidone

Phase 3

Bipolar I Disorder | Small molecule | Psychiatry |Vanda Pharmaceuticals Inc.|Last Updated: Feb 27, 2026

Target and mechanism

Molecular targetDRD2, HTR2A
Target classAntagonist
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLED
Total Trials2
Total Enrollment429

FDA Designations

No designations recorded

Clinical trial landscape

Iloperidone · 8 trials · 5 indications

Phase 3 4Phase 2 1Phase 1 3
NCT06961968Randomized Withdrawal Study in Patients With SchizophreniaSchizophrenia
RECRUITING400 Analytics
NCT04819776Evaluation of Efficacy and Safety of Iloperidone in the Acute Treatment of Manic or Mixed Episodes Associated With Bipolar I DisorderBipolar I Disorder
COMPLETED417 Analytics
NCT01291511Relapse Prevention Study in Patients With SchizophreniaSchizophrenia
COMPLETED635 Analytics
NCT00254202Efficacy and Safety of Iloperidone Compared With Placebo and Active Control in Subjects With Acute SchizophreniaSchizophrenia
COMPLETED593 Analytics
PHASE3RECRUITING
Randomized Withdrawal Study in Patients With Schizophrenia
SchizophreniaUnlock trial analytics
PHASE3COMPLETED
Evaluation of Efficacy and Safety of Iloperidone in the Acute Treatment of Manic or Mixed Episodes Associated With Bipolar I Disorder
Bipolar I DisorderUnlock trial analytics
PHASE3COMPLETED
Relapse Prevention Study in Patients With Schizophrenia
SchizophreniaUnlock trial analytics
PHASE3COMPLETED
Efficacy and Safety of Iloperidone Compared With Placebo and Active Control in Subjects With Acute Schizophrenia
SchizophreniaUnlock trial analytics

Study Endpoints

Primary Endpoints

Time to exacerbation of symptoms
Up to 52 weeks post-randomization

As measured by the time to first exacerbation of psychiatric symptoms

Change From Baseline to Week 4 in Young Mania Rating Scale (YMRS) Total Score
Week 4

The Young Mania Rating Scale (YMRS) is an 11-item scale. Individual item scores are summed for a total possible score of 0 (best) to 60 (worst).

Time to Relapse or Impending Relapse
Up to 26 weeks post-randomization

Relapse or impending relapse was defined as any of the following: hospitalization due to worsening of schizophrenia; increase (worsening) of the PANSS total score of greater than or equal to 30% from randomization, PANSS total score confirmed at a second visit conducted within 1-7 days; clinically significant emergent or worsening suicidal, homicidal, or aggressive behavior; a CGI-Improvement (CGI-I) score of 6 (much worse) or 7 (very much worse) after randomization; a dose increase in study medication or a need for additional open-label antipsychotic treatment.

Change From Baseline in Positive and Negative Symptom Scale Total (PANSS-T) Score
4 weeks

The PANSS is a 30-item scale developed to assess the severity of symptoms of schizophrenia. The PANSS items are divided into positive, negative, and general psychopathology factors. Items are rated on a scale of 1 (absent) to 7 (extremely severe). The PANSS-T score is the sum of scores for all 30 PANSS items (i.e., the sum of the three subscales), with a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms. A negative change from baseline indicates improvement.

Change from baseline to treatment week 4 in SiSBP
screening to treatment week 4
Pharmacokinetics of iloperidone and its metabolites following repeat-dosing of iloperidone given as a long-acting injection.
24 weeks

As measured by plasma concentrations.

Assessment of safety and tolerability of repeat-dosing of iloperidone given as a long-acting injection.
24 weeks

As measured by spontaneous reporting of adverse events (AEs).

The frequency of treatment-emergent adverse events as measured by the number of events
7 days
Pharmacokinetics of iloperidone at different dose levels based on AUC (area under the plasma concentration time curve during a dosage interval) Cmax ss (maximum plasma concentration at steady state), Tmax ss (time to Cmax at steady state).
Visit 5, 6, 7 (after at least 7 days of iloperidone treatment at the same dose level)

Pharmacokinetics describes the action of a drug in the body over a period of time. Blood samples are collected to measure plasma concentrations of the study drug at different times after dosing. From the plasma concentration data, AUC, Cmax ss, and Tmax ss are calculated.

Tolerability of iloperidone at different dose levels
14 days

Frequency of treatment emergent adverse events, frequency of clinically notable changes from baseline in vital signs, electrocardiograms, laboratory tests, and reponses on movement disorder rating scales (Barnes Akathisia Rating Scale, Simpson-Angus Scale) and on a rating scale for suicidal thoughts and behaviors (Columbia Suicide Severity Rating Scale)

Secondary Endpoints

PANSS Total Score, Change From Baseline to Last Visit
Up to 26 weeks post-randomization
CGI-S, Last Visit
Up to 26 weeks post-randomization
SDS Total Score, Change From Baseline to Last Visit
Up to 26 weeks post-randomization
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
iloperidoneEXPERIMENTALDuring the 12-week stabilization phase, all patients will receive open-label iloperidone administered as oral tablets (weeks 1-6) and as long-acting intramuscular injections (weeks 7-12). Subsequently, patients will be randomized in a 1:1 ratio to one of two arms: iloperidone long-acting injection or matching placebo. Post-randomization this arm will receive double-blind study drug (iloperidone long-acting injection) as long-acting intramuscular injections for up to 52 weeks.
placeboPLACEBO_COMPARATORDuring the 12-week stabilization phase, all patients will receive open-label iloperidone administered as oral tablets (weeks 1-6) and as long-acting intramuscular injections (weeks 7-12). Subsequently, patients will be randomized in a 1:1 ratio to one of two arms: iloperidone long-acting injection or matching placebo. Post-randomization this arm will receive double-blind study drug (matching placebo) as long-acting intramuscular injections for up to 52 weeks.
ZiprasidoneACTIVE_COMPARATOROral ziprasidone
Experimental/IloperidoneEXPERIMENTAL -
Placebo ComparatorPLACEBO_COMPARATOR -
CYP2D6 non-poor metabolizersOTHERtitrated up to 24 mg daily (12 mg b.i.d.)
CYP2D6 poor metabolizersOTHERtitrated up to 12 mg daily (6 mg b.i.d.)

Interventions

NameTypeDescription
iloperidoneDRUGiloperidone LAI
placeboDRUGmatching placebo
Iloperidone PlaceboDRUGOral placebo
ZiprasidoneDRUG -
iloperidone (oral tablet)DRUGiloperidone 12 to 24 mg/day followed by 26 weeks of flexible dosing (6 to 24 mg/day)
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Eligibility Criteria

Age Range18 Years to 65 Years
SexALL
Healthy VolunteersNo
Study Sites22

Inclusion Criteria: * Males or females 18 to 65 years of age (inclusive) * Diagnosed with schizophrenia per DSM-5 criteria * In need of ongoing psychiatric treatment Exclusion Criteria: * DSM-5 diagnosis of a psychiatric disorder other than schizophrenia that was the primary focus of treatment wi...

Countries:United StatesBulgariaPolandIndiaUkraine
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Frequently asked questions about Iloperidone

What is Iloperidone used for?

Iloperidone is an investigational small molecule being studied for the treatment of Bipolar I Disorder, Schizophrenia, and Hypertension. It is being developed by Vanda Pharmaceuticals Inc. (VNDA). The drug is currently in Phase 3 clinical trials for these indications.

What does Iloperidone target?

Iloperidone is a small molecule antipsychotic. Its mechanism of action involves targeting neurotransmitter receptors in the brain, specifically dopamine and serotonin receptors. This activity is believed to contribute to its therapeutic effects in psychiatric conditions like schizophrenia and bipolar disorder.

Who makes Iloperidone?

Iloperidone is being developed by Vanda Pharmaceuticals Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol VNDA. Vanda is conducting clinical trials to evaluate the drug's safety and efficacy for multiple indications.

What phase is Iloperidone in?

Iloperidone is in Phase 3 clinical development. It has completed a Phase 3 trial for the acute treatment of manic or mixed episodes associated with Bipolar I Disorder. The drug is also being studied in earlier phase trials for other conditions.

What clinical trials is Iloperidone in?

Iloperidone has been studied in several clinical trials. A completed Phase 3 trial (NCT04819776) evaluated its efficacy in treating manic or mixed episodes in Bipolar I Disorder. Other trials include a Phase 1 study (NCT04127058) on titration in bipolar disorder or schizophrenia, and a Phase 1 study (NCT04712734) on a long-acting injection for schizophrenia. A Phase 2 trial (NCT07090161) is currently recruiting patients with uncontrolled hypertension.

Is Iloperidone the same as Fanapt?

Iloperidone is the active ingredient in the antipsychotic medication Fanapt, which is approved for the treatment of schizophrenia. Vanda Pharmaceuticals is developing iloperidone for additional indications, including bipolar disorder and hypertension, under its generic name.