Randomized, Double-blinded, Placebo-controlled, Evaluating the Treatment With LB-102 in Patients With Acute Schizophrenia

This is a Phase 2, randomized, double-blind, placebo-controlled, multi-center inpatient study to examine the efficacy and safety of LB-102 in adult patients diagnosed with acutely exacerbated schizophrenia. The primary objective of the study is to assess the efficacy of LB-102 versus placebo in reducing Positive and Negative Syndrome Scale (PANSS) total scores at day 28 in approximately 350 adult inpatients with a DSM-5 diagnosis of schizophrenia. The secondary objectives of the study are to evaluate improvement in CGI-S, PANSS subscale and Marder Factor scores, safety and tolerability, and pharmacokinetics in adult inpatients with a DSM-5 diagnosis of schizophrenia. The duration of treatment of the study is 28 days (4 weeks). Patients in this study will be randomized 3:3:3:1 to receive either: placebo, 50 mg QD LB-102, 75 mg QD LB-102, or 100 mg QD LB-102; that is, ~105 patients will get placebo, ~105 will get 50 mg LB-102 QD, ~105 will get 75 mg LB-102 QD, ~35 will get 100 mg LB-102 QD. LB-102 will be dosed orally once a day. Pharmacokinetic data will be measured for the first 60 patients in this study.

Inclusion criteria

A patient will be eligible for inclusion in the study if they meet all of the following criteria:

• Patient who is able to provide written informed consent (as required by Institutional Review Board [IRB]) prior to the initiation of any protocol-required procedures.
• Must be willing to be hospitalized for the duration of the inpatient period of the study.
• Have stable living environment when not in a hospital.
• Male and female patients 18 to 55 years of age inclusive at the time of informed consent with a diagnosis of schizophrenia as defined by DSM-5 criteria and confirmed by the MINI 7.0.2 .
• Body mass index (BMI) must be ≥18 and ≤40 kg/m2.
• Patient who experiencing an acute exacerbation of psychotic symptoms, AND the patient requires hospitalization OR if already an inpatient at Screening, has been hospitalized for onset < 2 weeks for the current exacerbation.
• Patients who are experiencing an acute exacerbation of psychotic symptoms and marked deterioration of usual function as demonstrated by meeting ALL of the following criteria at the Screening and Baseline visits:

• Total PANSS score between 80 and 120, inclusive, and
• Score of ≥4 (moderate or greater) for ≥2 of the following Positive Scale (P) items: Item 1 (P1; delusions), Item 2 (P2; conceptual disorganization), Item 3 (P3; hallucinatory behavior), Item 6 (P6; suspiciousness/persecution), and
• CGI-S score ≥4 (moderately to severely ill).
• Have received previous antipsychotic treatment (dose and duration as per the label) and who showed a previous good response to such antipsychotic treatment (other than clozapine) in the last 12 months, according to the Investigator's opinion.
• Have history of relapse and/or exacerbation of symptoms when they were not receiving antipsychotic treatment.
• Patients willing to discontinue all prohibited psychotropic medications prior to Screening, if determined to be clinically appropriate by the Investigator, and not for the sole purpose of inclusion in the trial.

Exclusion criteria

A patient will be excluded from the study if they meet any of the following criteria:

Sex and Reproductive Status

• Sexually active females of childbearing potential and male patients who are not practicing 2 different methods of birth control with their partner during the trial and for 30 days after the last dose of trial medication or who would not remain abstinent during the trial and for 30 days after the last dose.
• Females who are breastfeeding or who have a positive pregnancy test result prior to receiving trial medication.
• Patients who presented with a first episode of schizophrenia.
• Improvement of ≥20% in total PANSS score between the Screening and Baseline assessments.
• History of treatment resistance to schizophrenia medications defined as failure to respond to 2 adequate courses of pharmacotherapy (dose and duration as per the label) or required clozapine within the last 12 months.
• Current DSM-5 Axis I diagnosis other than schizophrenia.
• Risk for suicidal behavior during the study.
• Risk of violent or destructive behavior.
• Patients with clinically significant tardive dyskinesia.
• Patients with a score of 3 on the Barnes Akathisia Rating Scale (BARS) global clinical assessment of akathisia.
• Patients who met DSM-5 criteria for substance abuse or dependence within the past 1 year.
• Patients with hypothyroidism or hyperthyroidism or clinically significant abnormal thyroid function.
• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
• Patients with insulin-dependent diabetes mellitus (i.e., any patient using insulin) are excluded. Patients with non-insulin-dependent diabetes mellitus may be eligible for the trial if their condition is stable as determined by satisfying ALL of the following criteria:

• Glycosylated hemoglobin (HbA1c) <7.0%, and
• Screening glucose must have been ≤125 mg/dL or ≤6.94 mmol/L (fasting) or <200 mg/dL or <11.1 mmol/L (nonfasting), and
• Patient had been maintained on a stable regimen of oral antidiabetic medication(s) for at least 28 days prior to Screening or diabetes had been well controlled by diet for at least 28 days prior to Screening, and
• Patient had no hospitalizations within the 12 months prior to Screening due to diabetes or complications related to diabetes, and
• Patient's diabetes should not be newly diagnosed during Screening for the trial.
• Patients with uncontrolled hypertension or symptomatic hypotension, or orthostatic hypotension
• Patients with known ischemic heart disease or any history of myocardial infarction, congestive heart failure.
• Patients with epilepsy or a history of seizures.
• Patients with a positive urine drug screen or a positive blood alcohol test.
• Patients with a history of alcohol use or substance use disorder (by DSM-5 criteria) within 12 months of Screening or a positive screen for drugs of abuse at Screening.
• The following laboratory test results are exclusionary:

• Platelets ≤75,000/µL or ≤75×109/L
• Hemoglobin ≤9 g/dL or ≤90 g/L
• Neutrophils, absolute ≤1000/µL or ≤1×109/L
• AST and ALT >2 × upper limit of normal (ULN)
• CPK >3 × ULN, unless discussed with and approved by the Medical Monitor
• Creatinine ≥2 mg/dL or ≥176.8 µmol/L
• Estimated creatinine clearance of <45 mL/min, calculated using the Cockcroft-Gault equation, at Screening
• HbA1c ≥7.0%
• Abnormal free T4 (during Screening), unless discussed with and approved by the Medical Monitor.
• Clinically significant abnormal finding on the triplicate set of electrocardiograms (ECGs) or evidence of any of the following cardiac conduction abnormalities at Screening.
• Patients who are currently taking oral antipsychotic medications, monoamine oxidase inhibitors (MAOIs), anticonvulsants (e.g., lamotrigine, Depakote), tricyclic antidepressants (e.g., imipramine, desipramine), selective serotonin reuptake inhibitors, and any other antidepressants or any other psychoactive medications (except lorazepam, zolpidem, zaleplon, eszopiclone, or similar benzodiazepines, diphenhydramine, benztropine, and propranolol). The medications should not be discontinued solely to make the patient eligible for enrollment in the study.
• Patients who received electroconvulsive therapy, or Transcranial Magnetic Stimulation (TMS).
• Patients with a history of neuroleptic malignant syndrome.
• Patients with a history of allergic response
• Prisoners or patients who were compulsorily detained (involuntarily hospitalized) for treatment of either a psychiatric or physical illness or have been in the last 6 months prior to the Screening Visit
• Patients who have participated in another clinical study in which they received an experimental or investigational drug agent within 3 months of Screening.

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