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

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

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 4 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 Part B-EXT) and patients with T2DM [Optional] (Part C).

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 and Part B-EXT - 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.

Inclusion Criteria:

1. Ability and willingness to participate in the study, give written informed consent, and comply with the study restrictions and all protocol procedures

2. Sex: male or female

3. Weight: >50 kg, inclusive, at screening

4. Age:

   1. For Part A 18 to 70 years, inclusive, at screening
   2. For Part B, Part B-EXT, and C 18 to 55 years, inclusive, at screening

5. Body Mass Index

   1. For Part A: ≥18.5 kg/m2 and ≤35.0 kg/m2, inclusive, at screening
   2. For Part B and Part B-EXT: ≥30.0 kg/m2 and ≤40.0 kg/m2, inclusive, at screening
   3. For Part C: ≥25.0 kg/m2 and ≤40.0 kg/m2, inclusive, at screening

6. Patients with T2DM for at least 6 months, having HbA1c of 6.5% to 8.5% (Part C)

Key Exclusion Criteria:

1. History or clinically significant active disease of the gastrointestinal, cardiovascular, hepatic, neurologic, renal, pancreatic, immunologic, dermatologic, endocrine, genitourinary, or hematologic system
2. Uncontrolled hypertension
3. History of type 1 diabetes mellitus
4. History or current diagnosis of acute or chronic pancreatitis or factors for pancreatitis
5. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 or subjects with suspected medullary thyroid carcinoma
6. 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