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.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: S1B-509 low dose; Drug: Placebo; Drug: S1B-509 High Dose

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.

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anita Clayton, MD; Phone Number: 4342434649; Email: AHC8V@hscmail.mcc.virginia
• Study Contact Backup: Name: Robert E Pyke, MD,PhD; Phone Number: 2033992390; Email: robertepyke@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Simultaneous oral dosing once daily with two to four placebos, for 48 weeks	Drug: Placebo; matched pills to S1B-509
Experimental: S1B-509 (proprietary combination of trazodone and bupropion) low dose; Simultaneous oral dosing once daily with two to four extended-release tablets or capsules of S1B-509, for 48 weeks	Drug: S1B-509 low dose; S1B-509 has multiple neurotransmitter activities; Other Names: proprietary combination of trazodone and bupropion at low dose
Experimental: S1B-509 (proprietary combination of trazodone and bupropion) high dose; twice the dose of "S1B-509 low dose"	Drug: S1B-509 High Dose; S1B-509 has multiple neurotransmitter activities; Other Names: proprietary combination of trazodone and bupropion at high dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Per cent weight change	100 (Weight at follow-up) - (weight at baseline)/(weight at baseline)	48 weeks
Proportion losing at least 5% body weight	(number of subjects (no. ss) per group losing at least 5% body weight)/(total no. ss/group	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Waist circumference	measured waist in inches or centimeters	48 weeks
Proportion losing 10%	per cent of patients per group losing ten percent weight, a substantial amount	48 weeks
Proportion losing 15%	per cent of patients per group losing a highly substantial amount of weight	48 weeks
Change in systolic blood pressure	average gain in systolic blood pressure per group	48 weeks
Change in diastolic blood pressure	average change in diastolic pressure per group	48 weeks
Change in Hemoglobin A1c	change in glycosylated hemoglobin, a measure of diabetes; normal is less than 6.5%	48 weeks
Change in Columbia suicidality screener	6 yes/no items, patient-rated screener on suicide ideation and behavior, "no" on each is best	48 weeks
Change in Personal Health Questionnaire, 9-item version	depression screener. Sum of 9 self-rated items from 0 (best) to 3 (worst).	48 weeks
Adverse events	Change in subjective (answer to "how have you felt" or objective findings	4 weeks
Change in Female Sexual Function Index, Female	19-item self-rated scale on sexual response, sum of ratings from 0 or 1 (worst) to 5 (best)	4 weeks
Change in International Index of Erectile Function, 5-item version	5-item self-rated scale on erectile function, sum of items rated from 1 (worst) to 5 (best)	4 weeks
Edmonton Obesity Staging System	Single-item categorical rating from 0 (normal) to 4 (severe)	4 weeks

Collaborators and Investigators

• Sponsor: S1 Biopharma, Inc.
• Investigators: Study Chair: Nicolas E Sitchon, B.S., S1 Biopharma, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): October 15, 2025
• Primary Completion (Estimated): June 15, 2027
• Study Completion (Estimated): December 15, 2027

Study Registration Dates

• First Submitted: July 15, 2024
• First Submitted That Met QC Criteria: July 18, 2024
• First Posted (Actual): July 24, 2024

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 13, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: S1B-509; diabetes
• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Loss; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Central Nervous System Depressants; Neurotransmitter Agents; Membrane Transport Modulators; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Cytochrome P-450 Enzyme Inhibitors; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Dopamine Agents; Antidepressive Agents; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Bupropion; Trazodone
• Other Study ID Numbers: S1B-509-2000

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No