The Efficacy and Safety of a Selective Estrogen Receptor Beta Agonist (LY500307) for Negative Symptoms and Cognitive Impairment Associated With Schizophrenia (Beta)

This is an interventional treatment trial for Schizophrenia focused on measuring schizophrenia, Estrogen receptor agonist, cognitive impairment, negative symptoms Read More

Inclusion Criteria:

• 18 to 65 years of age at study entry
• Male
• DSM IV-TR diagnosis of schizophrenia as confirmed by Structured Clinical Interview for DSM-IV-TR (SCID)
• Outpatient or inpatient status
• Mild to moderate overall disease severity as defined by a CGI-S score of less than or equal to 4 (moderately ill) at randomization
• Moderate levels of negative symptoms as defined by a PANSS negative symptom sub-score greater than or equal to 11.

• Clinical stability as defined by:

  1. No exacerbation of illness leading to an intensification of treatment in the opinion of the investigator within four weeks prior to randomization, and
  2. No change in antipsychotic medication for at least four weeks prior to randomization

Exclusion Criteria:

• Subjects with current acute, serious, or unstable medical conditions, including, but not limited to: inadequately controlled diabetes, asthma, COPD, severe hypertriglyceridemia, recent cerebrovascular accidents, acute systemic infection or immunologic disease, unstable cardiovascular disorders, malnutrition, or hepatic, renal gastroenterologic, respiratory, endocrinologic, neurologic, hematologic, or infectious diseases
• Known or suspected history of prostate cancer, breast cancer, or other clinically significant neoplastic disease (other than squamous cell or basal cell carcinoma of skin)
• Known or suspected history of deep venous thrombosis, stroke, venous thromboembolism, pulmonary embolism, paresis or paralysis that may be thrombogenic in origin
• Subjects currently receiving testosterone replacement therapy or drugs that influence the hypothalamus-pituitary-gonadal axis.
• Subjects who have clinically significant extrapyramidal signs (EPS) as defined by a score of >20 on the Simpson-Angus Scale (SAS)
• Clinically significant electrocardiogram (ECG) abnormality, including, but not limited to, a corrected QT interval (Bazett's; QTcB) >450 msec. Repeat ECGs may be conducted at the discretion of the principal investigator.
• Subjects with known medical history of Human Immunodeficiency Virus positive (HIV+) status
• Subjects with an active seizure disorder
• Subjects with implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, ventriculoperitoneal shunt, or other contraindication to undergoing an MRI scan
• Known IQ less than 70 based on medical history
• Current DSM IV-TR diagnosis of substance dependence (excluding caffeine and nicotine)
• Subjects who test positive for (1) Hepatitis C virus antibody or (2) Hepatitis B surface antigen (HBsAg) with or without positive Hepatitis B core total antibody
• Subjects with moderate to severe renal impairment as defined by creatinine clearance (CrCl) < 60 ml/min (measured by the Cockcroft-Gault equation) at screening. Repeat evaluation may be conducted at the discretion of the Principal Investigator.
• Subjects with hepatic impairment as defined by liver transaminases or total bilirubin > 3 × upper limit of normal (ULN). Repeat evaluation may be conducted at the discretion of the Principal Investigator.
• Subjects considered a high risk for suicidal acts - active suicidal ideation as determined by clinical interview OR any suicide attempt in 30 days prior to screening
• Subjects who have participated in a clinical trial with any pharmacological treatment intervention for which they received study-related medication in the four weeks prior to randomization OR subjects currently receiving treatment (within 1 dosing interval plus four weeks) with an investigational depot formulation of an antipsychotic medication
• Subjects who demonstrate overtly aggressive behavior or who are deemed to pose a substantial risk of danger in the Investigator's opinion