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Caplyta kəp-LY-tə
Trade namesCaplyta
Other namesLumateperone tosylate, ITI-007; ITI-722
  • 1-(4-Fluorophenyl)-4-(3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-butanone
Clinical data
Drug classAtypical antipsychotic[1]
Main usesSchizophrenia[1]
Side effectsSleepiness, dry mouth[1]
Routes of
By mouth
Typical dose42 mg OD[1]
External links
US NLMLumateperone
License data
Legal status
Protein binding97.4%[2]
MetabolismMultiple UGTs, CYP450s, and AKR enzymes[2]
Excretion<1% excreted unchanged in urine[2]
Chemical and physical data
Molar mass393.506 g·mol−1
3D model (JSmol)
  • [H][C@]12CCN(CCCC(=O)C3=CC=C(F)C=C3)C[C@@]1([H])C1=CC=CC3=C1N2CCN3C

Lumateperone, sold under the brand name Caplyta, is a medication used to treat schizophrenia.[1] It is taken by mouth.[2]

Common side effects include sleepiness and dry mouth.[1] Other side effects may include neuroleptic malignant syndrome, tardive dyskinesia, diabetes, weight gain, low white blood cells, seizures, and poor coordination.[2] It increases the risk of death in older people with dementia.[2] It is a atypical antipsychotic.[2]

was approved for medical use in the United States in 2019.[1] In the United States it costs about 1,400 USD per month as of 2021.[3]

Medical uses


Lumateperone is used to treat schizophrenia in adults.[4][5]


Lumateperone is at a dose of 42 mg dose (60 mg lumateperone tosylate), despite being studied at lower doses (14 and 28 mg) and a higher dose (84 mg).[2]


Receptor affinities[2]
Receptor Ki (nM)
5-HT2A 0
Dopamine receptor D1 41
Serotonin transporter 33
Dopamine receptor D2 32
Dopamine receptor D4 <100
Alpha-1A adrenergic receptor <100
Alpha-1B adrenergic receptor <100

Mechanism of action

Lumateperone acts as an antagonist of 5-HT2A receptor and antagonizes several dopamine receptor subtypes (D1, D2, and D4). It has moderate serotonin transporter reuptake inhibition. It has additional off-target antagonism at alpha-1 receptors, without appreciable antimuscarinic or antihistaminergic properties.[2]


After taking the medication by mouth, lumateperone reaches maximum plasma concentrations within 1–2 hours and has a terminal elimination half-life of 18 hours.[2] Lumateperone is a substrate for numerous metabolic enzymes, including various glucuronosyltransferase (UGT) isoforms (UGT1A1, 1A4, and 2B15), aldo-keto reductase (AKR) isoforms (AKR1C1, 1B10, and 1C4), and cytochrome P450 (CYP) enzymes (CYP3A4, 2C8, and 1A2).[2]

Lumateperone does not cause appreciable inhibition of any common CYP450 enzymes. It is not a substrate for p-glycoprotein.[2]


Lumateperone was approved for medical use in the United States in December 2019,[4][5] and became available in February 2020.[2]

The FDA approved lumateperone based on evidence from three clinical trials (Trial 1/NCT01499563, Trial 2/NCT02282761 and Trial 3/NCT02469155) that enrolled 818 adult participants with schizophrenia.[4] The trials were conducted at 33 sites in the United States.[4] Trials 1 and 2 provided data on the benefits and side effects of lumateperone, and Trial 3 provided data on side effects only.[4]

Three trials provided data for the approval of lumateperone.[4] In each trial, hospitalized participants with schizophrenia were randomly assigned to receive either lumateperone or a comparison treatment (placebo or active comparator) once daily for four weeks (Trials 1 and 2) or six weeks (Trial 3).[4] Neither the participants nor the health care providers knew which treatment was being given until after the trials were completed.[4]

Trials 1 and 2 provided data for the assessment of benefits and side effects through four weeks of therapy.[4] Benefit was assessed by measuring the overall improvement in the symptoms of schizophrenia.[4] Trial 3 provided data for the assessment of side effects only during six weeks of therapy.[4]

Society and culture


The failure of Study 401 caused Intra-Cellular's stock price to fall.[6][7] Their stock fell again on July 23, when the US Food and Drug Administration (FDA) canceled a Psychopharmacologic Drugs Advisory Committee meeting.[8][9]



Two Phase III lumateperone monotherapy studies were conducted and completed for the treatment of bipolar depression, those being trial Study 401 and Study 404.[10] A third trial, Study 402, aims to test lumateperone in addition to lithium or valproate,[11][7] the data pertaining this trial is due out in 2020.[12][7]

Study 401 was conducted solely in the United States while Study 404 was a global study and included patients from the US.[citation needed] Of the entire Study 404 population (381 patients), two-thirds were from Russia and Colombia. At the completion of the two monotherapy Phase III trials only Study 404 met its primary endpoint and one of its secondary endpoints.[13][14] In Study 404, patients received 42 mg lumateperone once daily or placebo for six weeks. Study 404 patients saw an improvement of depressive symptoms compared to placebo as documented by a change in MADRS total score of 4.6.[15]


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Lumateperone Monograph for Professionals". Retrieved 24 November 2021.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 "Caplyta- lumateperone capsule". DailyMed. Intra-Cellular Therapies, Inc. 27 December 2019. Retrieved 3 July 2020.
  3. "Lumateperone Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 24 November 2021.
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 "Drug Trials Snapshots: Caplyta". U.S. Food and Drug Administration. 20 December 2019. Retrieved 2 July 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  5. 5.0 5.1 "Drug Approval Package: Caplyta". U.S. Food and Drug Administration (FDA). 21 January 2020. Retrieved 1 July 2020.
  6. House DW, ed. (8 July 2019). "Intra-Cellular down 9% premarket on uneven results from lumateperone studies". Seeking Alpha. Retrieved 6 November 2019.
  7. 7.0 7.1 7.2 "Why Intra-Cellular Therapies Is Tanking Today". Retrieved 6 November 2019.
  8. "Lumateperone schizophrenia drug seems to hit snag". Retrieved 6 November 2019.
  9. "Lumateperone for schizophrenia shows safety, tolerability in long-term study". Retrieved 6 November 2019.
  10. "Intra-Cellular Therapies Announces Positive Top-line Results from a Phase 3 Trial of Lumateperone in Patients with Bipolar Depression" (Press release). Intra-Cellular Therapies Inc. 8 July 2019. Retrieved 6 November 2019 – via GlobeNewswire.
  11. "Intra-Cellular Therapies Announces Positive Top-line Results from a Phase 3 Trial of Lumateperone in Patients with Bipolar Depression" (Press release). Intra-Cellular Therapies Inc. 8 July 2019. Retrieved 6 November 2019 – via GlobeNewswire.
  12. "One out of two is not enough for Intra-Cellular". 8 July 2019. Retrieved 6 November 2019.
  13. "One out of two is not enough for Intra-Cellular". 8 July 2019. Retrieved 6 November 2019.
  14. DeArment A (8 July 2019). "Intra-Cellular Therapies hits one, misses another in Phase III bipolar disorder program". MedCity News. Retrieved 6 November 2019.
  15. "Phase 3 data supports lumateperone for bipolar depression". 8 July 2019. Retrieved 6 November 2019.

External links

External sites: