Pharmacokinetics, Safety, and Tolerability of Lumateperone Long-Acting Injectable in Patients With Schizophrenia

An Open-label Study to Determine the Pharmacokinetics, Safety and Tolerability of Single Ascending Doses of a Subcutaneous Injection of Lumateperone Long-Acting Injectable (LAI) Formulation in Patients With Schizophrenia

This is an open-label study to determine the pharmacokinetics, safety and tolerability of single ascending doses of lumateperone long-acting injectable formulation in patients with schizophrenia. Patients will be enrolled in one of up to four cohorts. All patients will receive oral lumateperone for 5 days, followed by a 5-day washout of oral lumateperone, then followed by a single dose of lumateperone LAI.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Lumateperone Long-Acting Injectable

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Clinical Site
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Male or female patients aged 18 to 50 years, inclusive
• Clinical diagnosis of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
• Clinically stable and free from acute exacerbation of psychosis for at least 3 months prior to Screening per Investigator assessment
• On a stable dose of antipsychotic medication, including lumateperone, for at least 3 months prior to the Screening Visit
• Clinical Global Impression - Severity (CGI-S) score ≤ 3

Key Exclusion Criteria:

• Clinically significant abnormality within 2 years of Screening that, in the Investigator's opinion, may place the patient at risk or interfere with study outcome variables
• History of psychiatric condition other than schizophrenia that, in the Investigator's opinion, may be detrimental to participation in the study
• Any suicidal ideation within the 6 months prior to Screening, any suicidal behavior within 2 years prior to Screening based on the Columbia-Suicide Severity Rating Scale (C-SSRS) (excluding self-injurious, non-suicidal behavior), and/or Investigator assessment that the patient is a safety risk to him/herself or others
• Surgical or medical condition (active or chronic) that in the Investigator's opinion may interfere with drug absorption, distribution, metabolism, or excretion of the study drug or any other condition that may place the patient at risk; history of gastric bypass or sleeve gastrectomy; history of severe dystonic reaction on antipsychotics such as laryngeal spasm

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: LAI Lumateperone 50 mg SC in the abdomen	Drug: Lumateperone Long-Acting Injectable; Lumateperone Long-Acting Injectable
Experimental: Cohort 2: LAI Lumateperone 100 mg SC in the abdomen	Drug: Lumateperone Long-Acting Injectable; Lumateperone Long-Acting Injectable
Experimental: Cohort 3: LAI Lumateperone 200 mg SC in the abdomen	Drug: Lumateperone Long-Acting Injectable; Lumateperone Long-Acting Injectable
Experimental: Cohort 4: LAI Lumateperone 100 or 200 mg SC in the outer area of the upper arm	Drug: Lumateperone Long-Acting Injectable; Lumateperone Long-Acting Injectable

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics: Maximum observed plasma concentration (Cmax) of lumateperone and metabolites	predose and at multiple timepoints up to 7 weeks postdose
Pharmacokinetics: Time of maximum observed plasma concentration (Tmax) of lumateperone and metabolites	predose and at multiple timepoints up to 7 weeks postdose
Pharmacokinetics: Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t) of lumateperone and metabolites	predose and at multiple timepoints up to 7 weeks postdose
Pharmacokinetics: Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of lumateperone and metabolites	predose and at multiple timepoints up to 7 weeks postdose
Pharmacokinetics: Terminal elimination half-life (T1/2) of lumateperone and metabolites	predose and at multiple timepoints up to 7 weeks postdose
Pharmacokinetics: Maximum observed plasma concentration (Cmax,BR) of lumateperone and metabolites during burst-release phase	predose and at multiple timepoints up to 7 weeks postdose
Pharmacokinetics: Time of maximum observed plasma concentration (Tmax,BR) of lumateperone and metabolites during burst-release phase	predose and at multiple timepoints up to 7 weeks postdose
Pharmacokinetics: Area under the plasma concentration-time curve (AUC0-t,BR) of lumateperone and metabolites during burst-release phase	predose and at multiple timepoints up to 7 weeks postdose
Pharmacokinetics: Maximum observed plasma concentration (Cmax,SR) of lumateperone and metabolites during sustained-release phase	predose and at multiple timepoints up to 7 weeks postdose
Pharmacokinetics: Time of maximum observed plasma concentration (Tmax,SR) of lumateperone and metabolites during sustained-release phase	predose and at multiple timepoints up to 7 weeks postdose
Pharmacokinetics: Area under the plasma concentration-time curve (AUC0-t,SR) of lumateperone and metabolites during sustained-release phase	predose and at multiple timepoints up to 7 weeks postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with treatment-emergent AEs		up to 7 weeks postdose
Change from baseline in Systolic and Diastolic Blood Pressure		up to 7 weeks postdose
Change from baseline in hemoglobin		up to 7 weeks postdose
Change from baseline in platelet count		up to 7 weeks postdose
Change from baseline in white blood cell count		up to 7 weeks postdose
Change from baseline in aspartate aminotransferase		up to 7 weeks postdose
Change from baseline in alanine aminotransferase		up to 7 weeks postdose
Change from baseline in glucose		up to 7 weeks postdose
Change from baseline in creatine kinase		up to 7 weeks postdose
Change from baseline in ECG QT Interval		up to 7 weeks postdose
Change from baseline in Abnormal Involuntary Movement Scale	AIMS is a measure of facial and oral movements, extremity movements and trunk movements. Items are rated on a scale from none (0) to severe (4).	up to 7 weeks postdose

Collaborators and Investigators

• Sponsor: Intra-Cellular Therapies, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2020
• Primary Completion (Actual): May 23, 2022
• Study Completion (Actual): May 23, 2022

Study Registration Dates

• First Submitted: December 29, 2020
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 14, 2021

Study Record Updates

• Last Update Posted (Actual): December 5, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: ITI-007-025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No