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

Phase IIb Placebo-Controlled Double-Blind Randomized Parallel Groups Study to Determine the Efficacy and Safety of S1B-509 for Weight Loss

This is a study to test whether S1B-509 given orally daily helps people with overweight or obesity to lose more weight than with placebo over a year.

This trial is to determine proof of concept for S1B-509 vs. placebo and to define a suitable dose escalation scheme and range for S1B-509 regarding safety, tolerability, and efficacy. The treatments will be given along with dietary advice and food intake monitoring. Change in body weight and in measures relating to obesity and its complications such as diabetes will be measured from baseline to week 48. Safety will be determined from adverse event reports, vital signs, routine laboratory tests, and mental health screeners.

Inclusion Criteria:

• 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.

Exclusion Criteria:

1. 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.
2. Use of alpha glucosidase inhibitors within 3 months of Visit 1, or between screening and randomization.
3. Bariatric surgery
4. 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
5. History of ketoacidosis, lactic acidosis, or hyperosmolar coma, or any of these occurring between Visit 1 and 2/randomization
6. Diabetics with HbA1c levels over 10 percent or fasting glucose levels greater than or equal to 270 mg/dl.
7. Symptomatic infection in the 4 weeks prior to screening or randomization.
8. Gastro-intestinal (GI) disorders associated with chronic diarrhea.
9. Congestive heart failure, New York Heart Association (NYHA) class III or IV
10. Body dysmorphic disorder or compulsive eating disorder
11. 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.
12. Requires CYP3A4, CYP 2B6, or CYP 2D6 strong inhibitor or inducer drugs
13. Takes any sex hormone other than an approved hormonal contraceptive
14. Takes an antiepileptic/mood stabilizer, antipsychotic, antidepressant, anxiolytic, or hypnotic drug
15. Drinks more than 7 alcoholic drinks per week (12-oz beer, 4-oz wine, 1 ½ oz liquor etc)
16. Uses marijuana more than once a week
17. History of seizures as an adult or use of antiepileptic medication
18. Long QT syndrome (QTc <=480 msec), other significant cardiovascular disease (hypertension controlled with one medication is acceptable)
19. Moderate or severe dysfunction of the liver (any LFT >=3x ULN) or renal dysfunction (BUN > 30 or Cr >2.0)
20. Uses sedating antihistamines or prescription sedatives daily
21. 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.