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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Lumateperone Long-Acting Injectable


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |