Obesity
Conditions
Keywords
S1B-509; diabetes
Brief summary
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.
Detailed description
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.
Interventions
DRUGS1B-509 low dose
S1B-509 has multiple neurotransmitter activities
DRUGPlacebo
matched pills to S1B-509
DRUGS1B-509 High Dose
S1B-509 has multiple neurotransmitter activities
Sponsors
S1 Biopharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
tablets of one of the actives and capsules of the other active matched to placebo tablets and capsules
Intervention model description
Parallel assignment to putatively active treatment at low and high dose or placebo
Eligibility
Sex/Gender
ALL
Age
25 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Per cent weight change | 48 weeks | 100 (Weight at follow-up) - (weight at baseline)/(weight at baseline) |
| Proportion losing at least 5% body weight | 48 weeks | (number of subjects (no. ss) per group losing at least 5% body weight)/(total no. ss/group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion losing 15% | 48 weeks | per cent of patients per group losing a highly substantial amount of weight |
| Change in systolic blood pressure | 48 weeks | average gain in systolic blood pressure per group |
| Change in diastolic blood pressure | 48 weeks | average change in diastolic pressure per group |
| Change in Hemoglobin A1c | 48 weeks | change in glycosylated hemoglobin, a measure of diabetes; normal is less than 6.5% |
| Change in Columbia suicidality screener | 48 weeks | 6 yes/no items, patient-rated screener on suicide ideation and behavior, no on each is best |
| Waist circumference | 48 weeks | measured waist in inches or centimeters |
| Adverse events | 4 weeks | Change in subjective (answer to how have you felt or objective findings |
| Change in Female Sexual Function Index, Female | 4 weeks | 19-item self-rated scale on sexual response, sum of ratings from 0 or 1 (worst) to 5 (best) |
| Change in International Index of Erectile Function, 5-item version | 4 weeks | 5-item self-rated scale on erectile function, sum of items rated from 1 (worst) to 5 (best) |
| Edmonton Obesity Staging System | 4 weeks | Single-item categorical rating from 0 (normal) to 4 (severe) |
| Change in Personal Health Questionnaire, 9-item version | 48 weeks | depression screener. Sum of 9 self-rated items from 0 (best) to 3 (worst). |
| Proportion losing 10% | 48 weeks | per cent of patients per group losing ten percent weight, a substantial amount |
Contacts
Primary ContactAnita Clayton, MD
Backup ContactRobert E Pyke, MD,PhD
Outcome results
None listed