A Study of LTX-001 In Adult Participants With Acute Exacerbation of Schizophrenia

Official title

A Phase 1b, Multicenter, Randomized, Double-Blind, Dose-Escalation, Placebo-Controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, And Early Signs of Efficacy of Orally Administered LTX-001 As Monotherapy in Adult Participants With Acute Exacerbation of Schizophrenia

Overview

The purpose of this clinical trial is to learn whether the investigational drug LTX-001 is safe and well tolerated in adults with a diagnosis of schizophrenia who are having a recent worsening of their symptoms (an acute exacerbation). Additional questions it aims to answer are: * how does the amount of the study drug in the body change over time (pharmacokinetics) * how does the study drug affect the symptoms of schizophrenia * how do certain markers in the blood change after administration of LTX-001 (pharmacodynamics) Researchers will compare different dose levels of LTX-001 to an inactive product (placebo) to see what differences there are between the two treatments. After successfully screening for the study, participants will stay in a research unit for about five weeks and return one week later for a follow-up visit.

Detailed description

After providing informed consent, eligible participants will be asked to visit the study site 3 times and stay overnight for 35 nights (up to 49 nights if up to 14 days of antipsychotic washout is applicable). Procedures will include:

* A review of medical history and medications * Physical exams, including a neurologic (nervous system) assessment * Electrocardiograms (a measure of the heart's electrical activity) * Blood and urine collection * Psychiatric assessments including the Mini International Neuropsychiatric Exam (MINI), the Brief Assessment of Cognition in Schizophrenia (BACS), and the Positive and Negative Syndrome Scale (PANSS) * Overall assessment of status via the Clinical Global Impression Scale - Severity (CGI-S) * Assessment of extrapyramidal symptoms (EPS) as assessed by the Modified Simpson-Angus Scale (M-SAS), the Abnormal Involuntary Movement Scale (AIMS) and the Barnes Akathisia Rating scale (BARS) * Assessment of suicidality risk via the Columbia Suicidality Severity Rating Scale (C-SSRS) * Quantitative electroencephalography (qEEG) assessments * Ophthalmologic examinations * Administration of the study drug (or placebo) by mouth

Interventions

• Drug LTX-001 once daily
  LTX-001 40 mg and 60 mg administered as oral suspension
• Drug Placebo
  Oral suspension without LTX-001
• Drug LTX-001 twice daily
  LTX-001 30 mg and 60 mg administered as oral suspension

Primary outcome measures

• Safety and Tolerability - Adverse Events [Time frame: Screening through Day 42]
• Safety and Tolerability - Clinical Laboratory Tests [Time frame: Screening through Day 42]
• Safety and Tolerability - Electrocardiograms (ECG) [Time frame: Screening through Day 42]
• Safety and Tolerability - Physical and Neurological Exams [Time frame: Screening through Day 42]
• Safety and Tolerability - Suicidality [Time frame: Screening through Day 42]
• Safety and Tolerability - Extrapyramidal Symptoms [Time frame: Screening through Day 42]
• Vital signs - blood pressure [Time frame: Screening through Day 42]
• Vital Signs - heart rate [Time frame: Screening through Day 42]
• Vital Signs - respiratory rate [Time frame: Screening through Day 42]
• Vital Signs - body temperature [Time frame: Screening through Day 42]

Secondary outcome measures (2)

• Pharmacokinetics of LTX-001 - Single Dose [Time frame: Days 1 and 8]
• Pharmacokinetics of LTX-001 - Multiple Dose [Time frame: Days 8 and 35]

Eligibility criteria

Inclusion criteria

• BMI > 17.5 and < 38.0 kg/m2 and a total body weight > 50.0 kg (110 lbs)
• Primary diagnosis of schizophrenia per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5-TR)
• Experiencing an acute exacerbation or relapse of symptoms, with onset less than 2 months prior to screening for the study
• PANSS total score ≥ 80 at the time of screening for the study
• Not currently on antipsychotic medication, or is willing to discontinue all prohibited psychotropic medications prior to and during the trial period
• Sexually active adults must be willing to use an acceptable contraceptive method throughout the study

Exclusion criteria

• Evidence of organ dysfunction or any clinically significant abnormal finding at physical examination
• History of treatment resistance (e.g., failure to respond to ≥ 2 adequate antipsychotic trials) or failure to respond to use of clozapine
• Current DSM-5-TR diagnosis other than schizophrenia
• Pregnant or lactating female
• Substance use disorder within 1 year prior to screening or recreational use of drugs within 3 months prior to screening
• Moderate to severe alcohol use disorder as per DSM-5-TR within the past year or excessive use of alcohol within 12 months prior to screening
• Positive testing for human immunodeficiency virus (HIV)-1 and -2 antibody, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody at screening

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 10 centers

• Pillar Clinical Research, LLC — Little Rock
• Collaborative Neuroscience Research, LLC — Los Alamitos
• University Clinical Research-DeLand, LLC d/b/a Accel Research Sites - DeLand Clinical Rese — DeLand
• Behavioral Clinical Research, Inc. — Hollywood
• CenExel Hollywood FL — Hollywood
• Innovative Clinical Research, Inc. — Miami Lakes
• CenExel iResearch, LLC — Decatur
• CBH Health LLC., dba CenExel Gaithersburg MD — Gaithersburg
• … and 2 more centers

Identifiers

NCT: NCT07734493 · LTX-001-103

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗