A Phase 2A Clinical Trial to Assess the Safety and Tolerability of ERX1000 in Men and Women for the Treatment of Obesity.

Prior treatment

• Lifetime history of DSM-5 diagnosis of schizophrenia or schizoaffective disorder. Diagnosis of bipolar 1 disorder within the previous 2 years.
• Type 1 diabetes mellitus or Type 2 diabetes mellitus or current or recent use of insulin (more than 1 week within 3 months prior to screening).
• Active autoimmune disease who are currently using or will likely require systemic glucocorticoid therapy in the next 6 months.
• Any previous surgical treatment or procedures with medical devices (such as insertion of lap band or gastric balloons) for obesity (excluding liposuction if performed \> 1 year prior to screening).
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair \> 6 months prior to Screening will be allowed).
• Current use, or within the 30 days prior to screening, of the following atypical antipsychotic medications:
  • Olanzapine
  • Clozapine
  • Quetiapine
• Subjects on any prescription or over-the-counter anti-obesity agents in the 3 months prior to screening (e.g., Saxenda, Wegovy, Zepbound, Xenical, Acutrim, Qsymia, Adipex, compounded peptides).
• Chronic (\>2 weeks) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, intra-articular, or inhaled preparations) within 1 month prior to study screening.
• Participation in any clinical study with an investigational drug/device within 3 months.
• Positive result for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) prior to initiation of dosing with study drug.
• Subjects who are planning or likely to undergo surgery during the course of the study.
• Subject is, in the opinion of the Investigator, not suitable to participate in the study (e.g., clinically significant illness in the 8 weeks before screening; unable to commit to study visits, etc.).

Other illness

• Poorly controlled severe psychiatric disorders (e.g., bipolar disorder, or major depressive disorder), recent (within 6 months) psychotic episodes, history of suicide attempts or suicidal ideation, or any other psychiatric disorders that the Investigator believes will interfere significantly with study compliance.
• History of any bleeding disorders, deep vein thrombosis (DVT), or thromboembolic disease.
• Obesity induced by other endocrine disorders (e.g., Prader-Willi syndrome, Cushing's syndrome).
• Uncontrolled endocrine disorders (e.g., Cushing syndrome, Addison's, Hashimoto's, hypothyroidism, hypogonadism).
• Recent (within the last year) and/or recurrent history of autonomic dysfunction (e.g., unexplained syncope or palpitations).
• Significant history of abuse of drugs or solvents in the year before screening, or history of alcohol abuse in the past year before screening or currently drinks in excess of 21 units or servings per week.
• Serious adverse reaction or hypersensitivity to any drug which the Investigator believes is clinically significant and relevant to study participation.

Lab values

• Current liver, renal, pulmonary, cardiac, oncologic, or gastrointestinal (GI) disease including:
  • Significant cardiovascular disease including history of congestive heart failure (CHF), coronary artery disease, myocardial infarction (MI), second degree or greater heart block, prolonged time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole (QT) syndrome, or clinically significant arrhythmias.
  • Fridericia-corrected QT interval (QTcF) \>460 msec for males and QTcF \>480 msec for females pre-dose on Day 1.
  • Liver disease or liver function tests, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \>1.5 upper limit of normal (ULN), alkaline phosphatase (ALP) or serum bilirubin \> ULN, or history of underlying liver disease including, hepatic cirrhosis, alcoholic hepatitis, or confirmed diagnosis of NASH; nonalcoholic fatty liver disease with qualifying LFTs will be allowed.
  • History or presence of impaired renal function as indicated by clinically significant abnormal creatinine, blood urea nitrogen (BUN), or urinary constituents or moderate to severe renal dysfunction as defined by the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation (\<60 mL/min/1.73m2).
• Clinically significant and abnormal screening hematology lab results or recurring infections, or if any of the following are observed regardless of the Investigator's assessment of clinical significance (laboratory tests may be repeated once for confirmation of out-of-range values):
  • Hemoglobin \<10 g/dL (\<100 g/L)
  • Absolute neutrophil count (ANC) \<2000/mm3
  • Platelets \<135 x 109/L
  • ALT or AST \> 1.5 ULN
  • GGT, ALP, total bilirubin, or INR \> ULN
• Results of screening clinical laboratory tests (complete blood count \[CBC\] with differential and platelets, chemistry, and urinalysis profile) and electrocardiogram (ECG) outside normal range and considered to be clinically significant by the Investigator.
• Subjects on the following systemic concomitant medications who have not been on stable dose (or stable weight-based dose), defined as no more than ±25% variation in dose, for at least 3 months prior to study entry:
  • Vasopressin
  • Thyroid hormone
  • Testosterone
  • Other hormone or hormone replacement therapies
  • Anti-diabetes medications other than metformin (e.g., glucagon-like peptide-1 \[GLP-1\] receptor agonists, sodium-glucose linked transporter 2 (SGLT2) inhibitors, sulfonylureas)
  • Modafinil
  • Atypical anti-psychotics, other than those noted above
  • Anti-depressives
  • Attention deficit hyperactivity disorder (ADHD) medications

Other

• Body weight of \> 350 pounds (158.8 kilograms) due to weight limits of the DEXA scanner.
• Vital signs unstable, or with the following values:
  • Systolic blood pressure \>160 mm Hg
  • Diastolic blood pressure \>100 mm Hg
  • Pulse rate \>100 beats per minute (bpm)
• Current or anticipated chronic use (more than 2 days) of narcotics or opiates.
• Significant blood loss or blood donation \>500 mL within 3 months.
• Females who are pregnant, nursing, or intend to become pregnant during the study.

• Able to comprehend and willing to sign an ICF and to abide by the study requirements.
• Male and female subjects ages 18-60 years, inclusive.
• BMI \>30 to \<50 kg/m2
• Stable body weight for 3 months (self-reported loss/gain \<5%).
• Stable diet and/or nutritional lifestyle for 3 months prior to randomization.
• If a subject has current diagnosis of prediabetes, the following criteria must be met:
  • Hemoglobin A1c (HbA1c) ≤6.4%
  • Fasting glucose ≤125 mg/dL (≤6.94 mmol/L)
  • No history of ketoacidosis or hyperosmolar coma
• Female subjects must not be pregnant or lactating. Nonpregnancy will be confirmed for all females by a urine pregnancy test conducted at Screening and at the Baseline Visit prior to enrollment into the study.
  • If of childbearing potential, the subject agrees to the use two of the following accepted contraceptive regimens from Screening to the first administration of the study drug, during the study, and for at least 30 days after the last dose of the study drug. Acceptable methods of contraception includes one of the following:
• Hormonal contraceptives (birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch), OR
• Intrauterine device (with or without hormones), AND
• Agrees to use a barrier method (e.g., male or female condom) during the study and for at least 30 days after the last dose of the study drug.