Study to Evaluate ARD-101 in Adults Receiving Bariatric Surgery

Study Overview
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Brief Summary
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The purpose of this study is to evaluate safety and efficacy of twice-daily ARD-101 in subjects at least one year after bariatric surgery (sleeve gastrectomy or gastric bypass).

Detailed Description
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This is a Phase 2, open-label study to investigate the safety and efficacy of twice-daily ARD-101 in subjects at least one year after bariatric surgery (sleeve gastrectomy or gastric bypass). This study has a planned enrollment of 30 subjects (approximately 15 for each preceding surgical procedure) and will be conducted in a single center in the United States. The study will consist of a Screening Period (up to 28 days), a Treatment Period (28 days), and a Follow-up Period (EOS Visit within 14 days after receiving the last dose of ARD-101). The screening procedures will be initiated upon completion of the informed consent process. Following completion of screening procedures and confirmation of eligibility, subjects will be enrolled to receive ARD-101.

Official Title
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A Phase 2 Open Label Study to Evaluate the Safety, Tolerability, and Efficacy of ARD-101 in Subjects At Least One Year After Bariatric Surgery

Conditions
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Bariatric Surgery, Obesity, Weight Gain

Intervention / Treatment
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* Drug: ARD-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects, 18-75 years of age Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures Body Mass Index (BMI) of 35-60 kg/m2 during the Screening Period Status of at least 1-year post sleeve gastrectomy or gastric bypass surgery. Subjects must have a documented weight loss of at least 50% of their excess weight at their nadir, and must have regained at least 20% of their nadir weight loss. Excess weight is defined as maximum preoperative weight - weight corresponding to a BMI of 25 kg/m2 Subjects with rescue surgery (e.g. gastric band to sleeve gastrectomy or gastric bypass; sleeve gastrectomy to gastric bypass) will be allowed, with time since second surgery of at least 12 months. Subjects with a history of revision procedures will be allowed if at least 6 months have passed since the procedure and weight has not deviated more than 5% in the 3 months prior to enrollment No abnormal findings or abnormalities of clinical significance in vital signs, physical examination, clinical laboratory tests (CBC, urinalysis, blood biochemistry, coagulation, pregnancy test (females), urine drug test, nicotine test, etc.), 12-lead electrocardiogram (ECG) during the Screening Period Serum creatinine, alkaline phosphatase, hepatic enzymes (aspartate aminotransferase, alanine aminotransferase) and total bilirubin (unless the subject has documented Gilbert syndrome) not exceeding 1.5-fold the upper laboratory norm and estimated Glomerular Filtration Rate (eGFR) >30 mL/min Standard 12-lead ECG parameters after 10minutes resting in supine position in the following ranges; 120 ms <PR <220 ms, QRS <120 ms, QTc <= 430 ms if male, <= 450 ms if female and normal ECG tracing unless the Investigator considers an ECG abnormality within described limits to be not clinically relevant Stable or well controlled blood pressure per Investigator's judgement during the Screening Period. Specifically: Vital signs after 10 minutes sitting in a chair (feet on floor, back supported): i. 95 mmHg < systolic blood pressure (SBP) <160 mmHg, ii. 45 mm Hg < diastolic blood pressure (DBP) <100 mm Hg, iii. 40 bpm < heart rate (HR) <100 bpm. Prediabetes- defined as a fasting blood glucose between 100-125 mg/dL OR an HbA1c between 5.7-6.5% at screening Type 2 diabetes- Defined as previous diagnosis by a healthcare professional OR a fasting blood glucose > 126 mg/dL OR HbA1c > 6.5% at screening. Patients with type 2 diabetes treated with metformin may be enrolled. However, patients with type 2 diabetes on any other therapy will be excluded. Female subjects must have negative serum pregnancy test and must not be lactating. For females able to bear children, a hormonal (i.e., oral, implantable, or injectable) and single barrier method (i.e., sponge), or a double-barrier method of birth control (i.e., condom with spermicide) or abstinence must be used/practiced throughout the study and for 90 days following last dose of study medication; for effective form of birth control. Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, bilateral tubal ligation, bilateral salpingectomy, or bilateral tubal occlusion) or post-menopausal for at least 12 months (may be confirmed with a screening follicle stimulating hormone (FSH) level in the post-menopausal lab range), do not require contraception during the study. Males with female partners of childbearing potential must agree to a double-barrier method if participants become sexually active during the study and for 90 days following the last dose of the study medication. Male subjects must not donate sperm for 90 days following their participation in the study. Exclusion Criteria: Any relevant gastrointestinal (GI) surgery (excluding the gastric bypass or sleeve gastrectomy) per Investigator judgement History of significant drug hypersensitivity or anaphylaxis Participation in a weight loss program or clinical trial for weight loss within the 3 months prior to enrollment Received any experimental drugs or devices or have participated in a clinical study within 30 days prior to enrollment Diabetes treatment (unless metformin as outlined), or chronic oral steroids, or treatment with immune modulators, anti-obesity drugs, chronic opiate therapy, or antipsychotic medications Currently receiving any drug-based therapy for weight management Thyroid-stimulating hormone (TSH) level is outside of normal limit during the Screening Period The presence of diseases with abnormal clinical manifestations that need to be excluded based on their possible contribution to weight loss or weight gain, including but not limited to nervous, cardiovascular, blood and lymphatic system, immune, renal, hepatic, gastrointestinal, respiratory, metabolic and skeletal diseases during the Screening Period History of myocardial infarction, unstable angina, arterial revascularization, stroke, New York Heart Association Functional Class II-IV heart failure, or transient ischemic attack within 6 months prior to Visit 1 Any malignancy not considered cured (except focal, treated basal cell carcinoma and squamous cell carcinoma of the skin); a participant is considered cured if there has been no evidence of cancer recurrence in the previous 5 years History of major depressive disorder or history of other severe psychiatric disorders (e.g., schizophrenia or bipolar disorder) within the last 2 years. Donated ≥200 mL of blood (blood components) or had massive blood loss, received blood transfusion or blood products within 3 months prior to enrollment Planned sperm/egg donation within 6 months post enrollment Positive urine drug test (morphine, methamphetamine, ketamine, ecstasy, and cannabis) during the Screening Period History of consuming more than 14 units of alcoholic beverages per week or of alcoholism or drug/chemical/substance abuse within past 2 years prior to enrollment (Note: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits) Smoking any amount within 3 months prior to enrollment Excessive consumption of tea, coffee, and/or caffeinated beverages (more than 8 cups, 250 mL for each cup) every day within 3 months prior to enrollment Symptomatic viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to enrollment History of human immunodeficiency virus antibody, hepatitis C antibody or hepatitis B virus surface antigen A history of psychiatric and psychological condition that, in the judgment of the investigator, may interfere with the planned treatment and follow-up, affect subject compliance or place the subject at high risk from treatment-related complications Poor venous access or inability to tolerate venipuncture Any condition or active drug treatment that the investigator or primary physician believes may not be appropriate for participating in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This study includes one intervention arm.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARD-101<br>Dose 200 mg of ARD-101, twice daily for 28 days | Drug: ARD-101<br>* Twice daily, oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Change in Body Weight (%) | The percent total weight change at the end of treatment from baseline | Run-in Visit (baseline), Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAE) | The incidence of treatment-emergent adverse events (TEAE) during the treatment period | Days 1-28 | 
| Change in Blood Lipid Concentrations | The change in blood lipid concentrations (total cholesterol, triglyceride, high density lipoprotein cholesterol, and low-density lipoprotein cholesterol) at the end of treatment from the baseline | Run-in Visit (baseline), Day 28 | 
| Change in Waist Circumference | The change in waist circumference at the end of treatment from the baseline | Run-in Visit (baseline), Day 28 | 
| Change in Hemoglobin A1c | The change in glycated hemoglobin (HbA1c) at the end of treatment from the baseline | Run-in Visit (baseline), Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Bariatric Surgery, Weight Gain, Anti-Obesity Agents