Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of MBX 1416 in Healthy Subjects and Patients With Postbariatric Hypoglycemia

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of MBX 1416 in healthy volunteers and patients with postbariatric hypoglycemia. This study includes 2 parts. Part A involves a single dose of MBX 1416 or placebo taken as a subcutaneous injection (SC). Part B involves repeat doses of MBX 1416 or placebo taken as a subcutaneous injection (SC).

Official Title
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Phase 1/2 Randomized, Double-Blind, Placebo-controlled, Single Ascending Dose Study in Healthy Volunteers and Multiple Ascending Dose Study in Patients With Postbariatric Hypoglycemia to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MBX 1416

Conditions
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Healthy, Postbariatric Hypoglycemia

Intervention / Treatment
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* Drug: MBX 1416 (Part A)
* Drug: MBX 1416 (Part B)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Part A Inclusion Criteria: Healthy men and women, between 18 and 65 years of age inclusive. Body mass index (BMI) ≥ 18 and ≤ 30 kg/m2 and stable body weight by history for ≥ 3 months. Fasting plasma glucose < 100 mg/dL and HbA1c < 5.7% Part A Exclusion Criteria: Use of weight-lowering pharmacotherapy or participation in a clinical weight control study. Subjects with a prior history of any serious adverse reaction, hypersensitivity or angioedema to GLP-1 receptor agonists. Presence of any clinically significant physical exam, ECG, or laboratory findings at screening. Part B Inclusion Criteria: Female and male adults, ages ≥ 18 and ≤ 65 years. BMI ≥ 25 kg/m2 to ≤ 35.0 kg/m2 and stable body weight by history for ≥ 3 months. Fasting plasma glucose < 100 mg/dL and HbA1c < 5.7%. Bariatric surgery (i.e., Roux-en-Y Gastric Bypass [RYGB]), or upper-gastrointestinal surgery (i.e., only vertical sleeve gastrectomy [VSG]) at least 6 months before screening. Patients with PBH identified by the following criteria: (Whipple's triad) (Salehi et al., 2018) experiencing post-prandial hypoglycemia occurring 1-3 hours after meals AND with documented hypoglycemia at the time of neuroglycopenic symptoms AND with resolution of symptoms after treatment to raise glucose. Patients must be able and willing to adhere to PBH dietary recommendations. Part B Exclusion Criteria: Patients with confirmed diabetes type 1 or type 2. Patients with dumping syndrome. Other reasons for hypoglycemia than PBH. Patients with a prior history of hypersensitivity or angioedema to GLP-1 receptor agonists, study drug or drug components. Current diagnosis of acute or chronic pancreatitis or factors for pancreatitis, such as cholelithiasis (without cholecystectomy) or alcohol abuse.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MBX 1416 (Part A)<br>Single ascending subcutaneous (SC) doses | Drug: MBX 1416 (Part A)<br>* Single Ascending subcutaneous (SC) dose of MBX 1416: 10mg, 30 mg,100mg, 200mg<br>|
| Experimental: MBX 1416 (Part B)<br>Repeated ascending subcutaneous (SC) doses | Drug: MBX 1416 (Part B)<br>* Repeated ascending subcutaneous (SC) doses of MBX 1416: 10mg, 30mg, 100mg<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Single dose or repeated subcutaneous (SC) dose of placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs), Serious Adverse Events (SAEs) |  | Baseline through Day 29 (Part A) or Day 45 (Part B) | 
| Maximum Plasma Concentration (Cmax) |  | Baseline through Day 29 (Part A) or Day 45 (Part B) |