Lumateperone

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Lumateperone
ITI-007.svg
Names
Pronunciation/lməˈtɛpərɑːn/
loo-mə-TE-pə-ron
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
use
By mouth
Typical dose42 mg OD[1]
External links
AHFS/Drugs.comMonograph
US NLMLumateperone
MedlinePlusa620014
Legal
License data
Legal status
Pharmacokinetics
Bioavailability4.4%[2]
Protein binding97.4%[2]
MetabolismMultiple UGTs, CYP450s, and AKR enzymes[2]
Excretion<1% excreted unchanged in urine[2]
Chemical and physical data
FormulaC24H28FN3O
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

Schizophrenia

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

Dosage

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]

Pharmacology

Receptor affinities[2]
Receptor Ki (nM)
5-HT2A 0
.54
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]

Pharmacokinetics

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]

History

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

Economics

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]

Research

Bipolar

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]

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Lumateperone Monograph for Professionals". Drugs.com. 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". finance.yahoo.com. Retrieved 6 November 2019.
  8. "Lumateperone schizophrenia drug seems to hit snag". www.mdedge.com. Retrieved 6 November 2019.
  9. "Lumateperone for schizophrenia shows safety, tolerability in long-term study". www.mdedge.com. 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". Evaluate.com. 8 July 2019. Retrieved 6 November 2019.
  13. "One out of two is not enough for Intra-Cellular". Evaluate.com. 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". www.healio.com. 8 July 2019. Retrieved 6 November 2019.

External links

External sites:
Identifiers: