XW014 in Healthy Subjects and Patients With Type 2 Diabetes Mellitus (T2DM)

Study Overview
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Brief Summary
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This is a Phase 1, randomized, double-blind, placebo-controlled, first-in-human (FIH) study to evaluate the safety, tolerability, food effect (FE), pharmacokinetics (PK), and pharmacodynamics (PD) of orally administered XW014 in healthy participants and patients with T2DM. This study will consist of 3 parts: a Single Ascending Dose (SAD) part in healthy subjects (Part A), and Multiple Ascending Dose (MAD) parts in healthy subjects with elevated BMI (Part B) and patients with T2DM (Part C).

Detailed Description
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Part A - SAD, including FE cohort: Healthy participants with BMI in the range of ≥18.5 kg/m2 to ≤35.0 kg/m2 will be randomized to receive a single oral dose of either XW014 or placebo in each of the planned SAD cohorts. Part B - MAD in healthy participants with elevated BMI: Healthy subjects with BMI in the range of ≥30 kg/m2 to ≤40.0 kg/m2 will be randomized to receive oral doses of XW014 or placebo in each of the planned MAD cohorts. Part C - MAD in patients with T2DM: Patients with T2DM for at least 6 months, having hemoglobin A1c (HbA1c) in the range of 6.5% to 8.5% will be randomized to receive oral doses of XW014 or placebo in each of the planned MAD cohorts.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Oral Dose Study to Assess Safety, Tolerability, Food Effect, Pharmacokinetics, and Pharmacodynamics of XW014 in Healthy Subjects and Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: XW014
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability and willingness to participate in the study, give written informed consent, and comply with the study restrictions and all protocol procedures Sex: male or female Weight: >50 kg at screening Age: For Part A 18 to 70 years, inclusive, at screening For Part B and C 18 to 55 years, inclusive, at screening Patients with T2DM for at least 6 months, having HbA1c of 6.5% to 8.5% (Part C) Exclusion Criteria: History or clinically significant active disease of the gastrointestinal, cardiovascular, hepatic, neurologic, renal, pancreatic, immunologic, dermatologic, endocrine, genitourinary, or hematologic system Uncontrolled hypertension History of type 1 diabetes mellitus History or current diagnosis of acute or chronic pancreatitis or factors for pancreatitis Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 or subjects with suspected medullary thyroid carcinoma Existence of any surgical or medical condition that, in the judgment of the Investigator, might interfere with the absorption, distribution, metabolism, or excretion of the investigational product

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SAD Cohort A - XW014<br>Single oral XW014 administration | Drug: XW014<br>* Oral capsules<br>|
| Placebo Comparator: SAD Cohort A - Placebo<br>Single oral placebo administration | Drug: Placebo<br>* Matched oral placebo capsules<br>|
| Active Comparator: MAD Cohort B - XW014<br>MAD in Healthy Subjects with Elevated BMI | Drug: XW014<br>* Oral capsules<br>|
| Placebo Comparator: MAD Cohort B - Placebo<br>MAD in Healthy Subjects with Elevated BMI | Drug: Placebo<br>* Matched oral placebo capsules<br>|
| Active Comparator: MAD Cohort C - XW014<br>MAD in Patients with T2DM | Drug: XW014<br>* Oral capsules<br>|
| Placebo Comparator: MAD Cohort C - Placebo<br>MAD in Patients with T2DM | Drug: Placebo<br>* Matched oral placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of treatment emergent adverse events (TEAE) and serious adverse events (SAE) |  | 11 weeks | 
| Mean change from baseline in clinical laboratory values, vital signs, clinical findings from physical exam and ECG abnormalities |  | 11 weeks |