One-Year Study of S1B-509 vs Placebo for Weight Loss

Prior treatment

• Use of alpha glucosidase inhibitors within 3 months of Visit 1, or between screening and randomization.
• Bariatric surgery
• Lack of compliance with lifestyle intervention (defined as weight gain during 4-week Screening/run-in or with study medication (defined as \< 80% study drug intake in more than one 4-week period
• Symptomatic infection in the 4 weeks prior to screening or randomization.
• Chronic conditions that may in the investigator's judgment be expected to be unstable and affect overall health are not allowed. Examples: gastrointestinal bleeding in prior 6 months, diabetes mellitus with HB A1C \>8.9, asthma not well controlled with treatment once or twice daily, current Major Depressive Disorder or recurrence of MDD off treatment for at least 2 months, anxiety disorder severe enough to prevent employment, severe sleep apnea, history within the prior year of suicidality or drug abuse, history of active breast, cervical, uterine, ovarian or other systemic cancer within the prior 24 months.
• Requires CYP3A4, CYP 2B6, or CYP 2D6 strong inhibitor or inducer drugs
• Takes an antiepileptic/mood stabilizer, antipsychotic, antidepressant, anxiolytic, or hypnotic drug

Other illness

• History of ketoacidosis, lactic acidosis, or hyperosmolar coma, or any of these occurring between Visit 1 and 2/randomization
• Gastro-intestinal (GI) disorders associated with chronic diarrhea.
• Congestive heart failure, New York Heart Association (NYHA) class III or IV
• Body dysmorphic disorder or compulsive eating disorder
• History of seizures as an adult or use of antiepileptic medication
• History of blood clots or abnormal bleeding tendencies, including daily use of medications adversely affecting coagulation, e.g., NSAIDs, systemic corticosteroids, or \>81 mg aspirin daily.

Lab values

• Use of pharmacologically active weight-loss medications, glucagon-like peptide-1 (GLP-1) agonists or sodium-glucose co-transporter 2 (SGLT2) inhibitors, within 3 months of screening, or between screening and randomization.
• Diabetics with HbA1c levels over 10 percent or fasting glucose levels greater than or equal to 270 mg/dl.
• Long QT syndrome (QTc \<=480 msec), other significant cardiovascular disease (hypertension controlled with one medication is acceptable)
• Moderate or severe dysfunction of the liver (any LFT \>=3x ULN) or renal dysfunction (BUN \> 30 or Cr \>2.0)

Other

• Takes any sex hormone other than an approved hormonal contraceptive
• Drinks more than 7 alcoholic drinks per week (12-oz beer, 4-oz wine, 1 ½ oz liquor etc)
• Uses marijuana more than once a week
• Uses sedating antihistamines or prescription sedatives daily

• Patients with obesity disease and inadequately controlled body weight with diet and/or exercise
• Body mass index (BMI) ≥ 27 kg/m2 with significant comorbidity, e.g., type 2 diabetes, hypertension, dyslipidemia, sleep apnea, cardiovascular disease
• Waist circumference at umbilical level ≥ 85 cm for male, ≥ 90 cm for female
• Visceral fat area ≥ 100 cm2
• Agreement to comply with the study-required life-style intervention and treatment during the full duration of the study.
• Side effects from any continuing concomitant medications must be mild and stable or nil.
• Females: not pregnant or lactating for six months; using medically reliable contraception, i.e., diaphragm or (male or female) condom and spermicide, IUD, tubal sterilization, hormonal contraception (oral, vaginal, or implant), or (if the investigator finds the patient credibly monogamous) vasectomy of male partner.
• Gives informed consent for and is willing to undergo all of the scheduled evaluations.
• Prompt for screening and baseline visits, is cooperative, and takes reasonable directions without excessive explanations.