Study to Evaluate ARD-101 in Adults Receiving Bariatric Surgery
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ARD-101 Dose 200 mg of ARD-101, twice daily for 28 days |
Drug: ARD-101
Twice daily, oral administration
|
Outcome Measures
Primary Outcome Measures
- Relative Change in Body Weight (%) [Run-in Visit (baseline), Day 28]
The percent total weight change at the end of treatment from baseline
Secondary Outcome Measures
- Incidence of treatment-emergent adverse events (TEAE) [Days 1-28]
The incidence of treatment-emergent adverse events (TEAE) during the treatment period
- Change in Blood Lipid Concentrations [Run-in Visit (baseline), Day 28]
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
- Change in Waist Circumference [Run-in Visit (baseline), Day 28]
The change in waist circumference at the end of treatment from the baseline
- Change in Hemoglobin A1c [Run-in Visit (baseline), Day 28]
The change in glycated hemoglobin (HbA1c) at the end of treatment from the baseline
Other Outcome Measures
- Categorical Weight Loss [Run-in Visit (baseline), Day 28]
Proportion of subjects who lose < 5% and ≥ 5% initial weight
- Circulating Levels of Glucagon-like peptide (GLP)-1 (pmol) during Mixed-Meal Tolerance Test (MMTT) at Baseline and on Day 28, and Prior to and Post Dosing on Day 1 [Run-in Visit (baseline), Day 1, Day 28]
Circulating levels of glucagon-like peptide (GLP)-1 (pmol) prior to (negative timepoints) and post (positive timepoints) the Ensure meal given for mixed-meal tolerance test (MMTT) at baseline (run-in visit) and on day 28, and pre-dosing and 1 and 2 hours post the first dosing on day 1.
- Circulating Levels of Cholecystokinin (CCK) (pg/mL) during MMTT at Baseline and on Day 28, and Prior to and Post Dosing on Day 1 [Run-in Visit (baseline), Day 1, Day 28]
Circulating levels of cholecystokinin (CCK) (pg/mL) prior to (negative timepoints) and post (positive timepoints) the Ensure meal given for MMTT at baseline (run-in visit) and on day 28, and pre-dosing and 1 and 2 hours post the first dosing on day 1.
- Circulating Levels of Peptide YY (PYY) (pg/mL) during MMTT at Baseline and on Day 28, and Prior to and Post Dosing on Day 1 [Run-in Visit (baseline), Day 1, Day 28]
Circulating levels of peptide YY (PYY) (pg/mL) prior to (negative timepoints) and post (positive timepoints) the Ensure meal given for MMTT at baseline (run-in visit) and on day 28, and pre-dosing and 1 and 2 hours post the first dosing on day 1.
- Circulating Levels of Amylin (pmol) during MMTT at Baseline and on Day 28, and Prior to and Post Dosing on Day 1 [Run-in Visit (baseline), Day 1, Day 28]
Circulating levels of amylin (pmol) prior to (negative timepoints) and post (positive timepoints) the Ensure meal given for MMTT at baseline (run-in visit) and on day 28, and pre-dosing and 1 and 2 hours post the first dosing on day 1.
- Circulating Levels of Glucose-dependent Insulinotropic Polypeptide (GIP) (pg/mL) during MMTT at Baseline and on Day 28, and Prior to and Post Dosing on Day 1 [Run-in Visit (baseline), Day 1, Day 28]
Circulating levels of glucose-dependent insulinotropic polypeptide (GIP) (pg/mL) prior to (negative timepoints) and post (positive timepoints) the Ensure meal given for MMTT at baseline (run-in visit) and on day 28, and pre-dosing and 1 and 2 hours post the first dosing on day 1.
- Circulating Levels of Ghrelin (pg/mL) during MMTT at Baseline and on Day 28, and Prior to and Post Dosing on Day 1 [Run-in Visit (baseline), Day 1, Day 28]
Circulating levels of ghrelin (pg/mL) prior to (negative timepoints) and post (positive timepoints) the Ensure meal given for MMTT at baseline (run-in visit) and on day 28, and pre-dosing and 1 and 2 hours post the first dosing on day 1.
- Circulating Levels of Leptin (ng/mL) during MMTT at Baseline and on Day 28, and Prior to and Post Dosing on Day 1 [Run-in Visit (baseline), Day 1, Day 28]
Circulating levels of leptin (ng/mL) prior to (negative timepoints) and post (positive timepoints) the Ensure meal given for MMTT at baseline (run-in visit) and on day 28, and pre-dosing and 1 and 2 hours post the first dosing on day 1.
- Circulating Levels of Adiponectin (mcg/mL) during MMTT at Baseline and on Day 28, and Prior to and Post Dosing on Day 1 [Run-in Visit (baseline), Day 1, Day 28]
Circulating levels of adiponectin (mcg/mL) prior to (negative timepoints) and post (positive timepoints) the Ensure meal given for MMTT at baseline (run-in visit) and on day 28, and pre-dosing and 1 and 2 hours post the first dosing on day 1.
- Circulating Levels of Glucagon (pg/mL) during MMTT at Baseline and on Day 28, and Prior to and Post Dosing on Day 1 [Run-in Visit (baseline), Day 1, Day 28]
Circulating levels of glucagon (pg/mL) prior to (negative timepoints) and post (positive timepoints) the Ensure meal given for MMTT at baseline (run-in visit) and on day 28, and pre-dosing and 1 and 2 hours post the first dosing on day 1.
- Serum Levels of Glucose (mg/dL) during MMTT at Baseline and on Day 28 [Run-in Visit (baseline), Day 28]
Serum levels of glucose (mg/dL) prior to (negative timepoints) and post (positive timepoints) the Ensure meal given for MMTT at baseline (run-in visit) and on day 28.
- Serum Levels of Insulin (uIU/mL) during MMTT at Baseline and on Day 28 [Run-in Visit (baseline), Day 28]
Serum levels of insulin (uIU/mL) prior to (negative timepoints) and post (positive timepoints) the Ensure meal given for MMTT at baseline (run-in visit) and on day 28.
- Serum Levels of C-peptide (ng/mL) during MMTT at Baseline and on Day 28 [Run-in Visit (baseline), Day 28]
Serum levels of C-peptide (ng/mL) prior to (negative timepoints) and post (positive timepoints) the Ensure meal given for MMTT at baseline (run-in visit) and on day 28.
- Serum Levels of Free Fatty Acids during MMTT at Baseline and on Day 28 [Run-in Visit (baseline), Day 28]
Serum levels of free fatty acids (FFA) prior to (negative timepoints) and post (positive timepoints) the Ensure meal given for MMTT at baseline (run-in visit) and on day 28.
- Circulating Levels of Interleukin (IL)-1 beta (pg/mL) during MMTT [Run-in Visit (baseline), Day 28]
Circulating levels of interleukin (IL)-1 beta (pg/mL) at run in visit and end of treatment (day 28) performed during the MMTT
- Circulating Levels of IL-6 (pg/mL) during MMTT [Run-in Visit (baseline), Day 28]
Circulating levels of IL-6 (pg/mL) at run in visit and end of treatment (day 28) performed during the MMTT
- Circulating Levels of IL-10 (pg/mL) during MMTT [Run-in Visit (baseline), Day 28]
Circulating levels of IL-10 (pg/mL) at run in visit and end of treatment (day 28) performed during the MMTT
- Circulating Levels of IL-12 p40 (pg/mL) during MMTT [Run-in Visit (baseline), Day 28]
Circulating levels of IL-12 p40 (pg/mL) at run in visit and end of treatment (day 28) performed during the MMTT
- Circulating Levels of IL-12 p70 (pg/mL) during MMTT [Run-in Visit (baseline), Day 28]
Circulating levels of IL-12 p70 (pg/mL) at run in visit and end of treatment (day 28) performed during the MMTT
- Circulating Levels of IL-17 (pg/mL) during MMTT [Run-in Visit (baseline), Day 28]
Circulating levels of IL-17 (pg/mL) at run in visit and end of treatment (day 28) performed during the MMTT
- Circulating Levels of Tumor Necrosis Factor (TNF)-alpha (pg/mL) during MMTT [Run-in Visit (baseline), Day 28]
Circulating levels of tumor necrosis factor (TNF)-alpha (pg/mL) at run in visit and end of treatment (day 28) performed during the MMTT
- Circulating Levels of C Reactive Protein (CRP) (mg/L) during MMTT [Run-in Visit (baseline), Day 28]
Circulating levels of C reactive protein (CRP) (mg/L) at run in visit and end of treatment (day 28) performed during the MMTT
- Body Fat Percentage [Run-in Visit (baseline), Days 1-28]
Body fat percentage measured by bioelectrical impedance scale
- Change in the Percentage of Liver Fat Content [Run-in Visit (baseline), Day 28]
Change in the percentage of liver fat content assessed by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF)
- Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [Run-in Visit (baseline), Day 28]
The change in homeostatic model assessment for insulin resistance (HOMA-IR) at the end of treatment from the baseline
- Change in Fasting Blood Glucose [Run-in Visit (baseline), Day 28]
The change in fasting blood glucose at the end of treatment from the baseline
- Change in Serum Bile Acids [Run-in Visit (baseline), Day 28]
Change in serum bile acids at the end of treatment compared to the baseline
- Phenotypic Taste Test [Run-in Visit (baseline)]
Phenotypic taste test (using commercially available test strips) at baseline
- Control of Eating and Food Cravings [Screening, Days 1, 15, and 28]
Control of eating and food craving assessed by the Control of Eating Questionnaire (CoEQ), which is a 21-item questionnaire designed to assess the intensity and type of food cravings and subjective sensations of appetite and mood according to an individual's experience over the last 7 days. Items on the CoEQ are assessed by 100-mm visual analogue scales (VAS). Subjects will mark their level with a vertical line on the horizontal line of the VAS scale. The numerical value will start at 1.0 cm and end 10.0 cm. Use a ruler to determine the numerical value (to the tenth decimal) associated with the line marked by subjects. Higher score indicates less control of eating and food cravings.
- Change in Indirect Calorimetry [Day 1, Day 28]
Change in indirect calorimetry between Day 1 and Day 28
- Area under the Curve (AUC) of Serum Level of Glucose (mg/dL) during MMTT [Run-in Visit (baseline), Day 28]
Changes in AUC of serum level of glucose (mg/dL) during MMTT between baseline and Day 28
- Area under the Curve (AUC) of Serum Level of Insulin (uIU/mL) during MMTT [Run-in Visit (baseline), Day 28]
Changes in AUC of serum level of insulin (uIU/mL) during MMTT between baseline and Day 28
- Area under the Curve (AUC) of Serum Level of C-peptide (ng/mL) during MMTT [Run-in Visit (baseline), Day 28]
Changes in AUC of serum levels of C-peptide (ng/mL) during MMTT between baseline and Day 28
- Changes in Fecal Microbial Species and Their Relative Abundance [Day 1, Day 28]
Changes in fecal microbial species and their relative abundance assessed by 16S rRNA gene sequencing
Eligibility Criteria
Criteria
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):
- 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
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Diabetes treatment (unless metformin as outlined), or chronic oral steroids, or treatment with immune modulators, anti-obesity drugs, chronic opiate therapy, or antipsychotic medications
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Currently receiving any drug-based therapy for weight management
-
Thyroid-stimulating hormone (TSH) level is outside of normal limit during the Screening Period
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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
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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.
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Donated ≥200 mL of blood (blood components) or had massive blood loss, received blood transfusion or blood products within 3 months prior to enrollment
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Planned sperm/egg donation within 6 months post enrollment
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Positive urine drug test (morphine, methamphetamine, ketamine, ecstasy, and cannabis) during the Screening Period
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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)
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Smoking any amount within 3 months prior to enrollment
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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
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Symptomatic viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to enrollment
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History of human immunodeficiency virus antibody, hepatitis C antibody or hepatitis B virus surface antigen
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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
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Any condition or active drug treatment that the investigator or primary physician believes may not be appropriate for participating in the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Altman Clinical and Translational Research Institute, University of California, San Diego | San Diego | California | United States | 92037 |
Sponsors and Collaborators
- Aardvark Therapeutics, Inc.
- University of California, San Diego
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AARD-202