Lumateperone

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Lumateperone
Clinical data
Pronunciation/luːməˈtɛpərɑːn/
loo-mə-TE-pə-ron
Trade namesCaplyta
Other namesITI-007; ITI-722
AHFS/Drugs.comMonograph
MedlinePlusa620014
License data
Routes of
administration		By mouth
Drug classAtypical antipsychotic
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability4.4%[2]
Protein binding97.4%[2]
MetabolismMultiple UGTs, CYP450s, and AKR enzymes[2]
Excretion<1% excreted unchanged in urine[2]
Identifiers
  • 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
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 an

Bristol-Myers Squibb.[3] Lumateperone was approved for medical use in the United States in December 2019 with an initial indication for schizophrenia,[4][5] and became available in February 2020.[2]
It has since demonstrated efficacy in bipolar depression and received FDA approval in December 2021 for depressive episodes associated with both bipolar I and II disorders.

Medical uses

Schizophrenia

On December 20, 2019, the United States Food and Drug Administration (FDA) approved lumateperone for the treatment of schizophrenia in adults.[4][5][6]

Bipolar depression

In December 2021, the FDA approved lumateperone for the treatment of bipolar depression in adults as monotherapy and as adjunctive therapy with lithium or valproate.[2][7] The number needed to treat (NNT) for bipolar depression at a dose of 42 mg daily is 7 patients.

Adverse effects

The most common adverse effects (≥5%) were somnolence and dry mouth.[8]

Lumateperone is associated with a low rate of serum

acute liver injury.[9]

Pharmacology

Receptor affinities[2]
Site Ki (nM)
SERT 33
5-HT2A
 0.54
α1A <100
α1B <100
D1 41
D2 32
D4 <100

Mechanism of action

Lumateperone acts as a

5-HT2A receptor and antagonizes several dopamine receptors (D1, D2, and D4) with lower affinity. It has moderate serotonin transporter reuptake inhibition. It has additional off-target antagonism at α1 receptors, without appreciable antimuscarinic or antihistaminergic properties, limiting side effects associated with other atypical antipsychotics.[2]

Pharmacokinetics

After taking the medication by mouth, lumateperone reaches

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

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]

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][12] the data pertaining this trial is due out in 2020.[13][12]

Study 401 was conducted solely in the United States while Study 404 was a global study and included patients from the US.[14][15] 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.[16][17] 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.[18]

References

  1. FDA
    . Retrieved 22 October 2023.
  2. ^ a b c d e f g h i j k l m "Caplyta- lumateperone capsule". DailyMed.nlm.nih.gov. US: National Library of Medicine, National Institutes of Health. 27 December 2019. Retrieved 3 July 2020.
  3. ISBN 978-3-319-11502-3
    .
  4. ^ a b c d e f g h i j k "Drug Trials Snapshots: Caplyta". U.S. Food and Drug Administration (FDA). 20 December 2019. Retrieved 2 July 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  5. ^ a b "Drug Approval Package: Caplyta". U.S. Food and Drug Administration (FDA). 21 January 2020. Retrieved 1 July 2020.
  6. ^ "FDA Approves Intra-Cellular Therapies' Novel Antipsychotic, Caplyta (lumateperone) for the Treatment of Schizophrenia in Adults" (Press release). Intra-Cellular Therapies Inc. 23 December 2019. Retrieved 1 July 2020 – via GlobeNewswire.
  7. ^ "Intra-Cellular Therapies Announces U.S. FDA Approval of CAPLYTA® (Lumateperone) for the Treatment of Bipolar Depression in Adults | Intra-Cellular Therapies Inc".
  8. ^ FDA Professional Drug Information
  9. PMID 34648250. Public Domain This article incorporates text from this source, which is in the public domain
    .
  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. ^ a b "Why Intra-Cellular Therapies Is Tanking Today". Yahoo! Finance. 8 July 2019. Retrieved 6 November 2019.
  13. ^ "One out of two is not enough for Intra-Cellular". Evaluate. 8 July 2019. Retrieved 6 November 2019.
  14. ^ "One out of two is not enough for Intra-Cellular". Evaluate. 8 July 2019. Retrieved 6 November 2019.
  15. ^ DeArment A (8 July 2019). "Intra-Cellular Therapies hits one, misses another in Phase III bipolar disorder program". MedCity News. Retrieved 6 November 2019.
  16. ^ "One out of two is not enough for Intra-Cellular". Evaluate. 8 July 2019. Retrieved 6 November 2019.
  17. ^ DeArment A (8 July 2019). "Intra-Cellular Therapies hits one, misses another in Phase III bipolar disorder program". MedCity News. Retrieved 6 November 2019.
  18. ^ "Phase 3 data supports lumateperone for bipolar depression". Healio. 8 July 2019. Retrieved 6 November 2019.

External links

  • "Lumateperone". Drug Information Portal. U.S. National Library of Medicine.
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