XW004 To Evaluate the Safety, Tolerability, PK, and PD of Oral Ecnoglutide Tablet in Healthy Adults

Study Overview
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Brief Summary
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XW004 is an acylated human glucagon-like peptide 1 (GLP-1) analogue and is being developed for type 2 diabetes mellitus (T2DM) and obesity management.

Detailed Description
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This is a single-centre, double-blind, randomised, multiple ascending dose, placebo-controlled study including four cohorts. All cohorts will have treatment regimens consisting of 15-day once daily dosing and a follow-up visit 21 days after last dosing. Participants will undergo a Screening period beginning up to 28 days prior to randomisation/dose administration.

Official Title
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A Phase 1, Randomised, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral Ecnoglutide Tablet in Healthy Adult Participants

Conditions
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Obesity, Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: XW004
* Drug: T2026
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female participants, aged 18 to 55 years (inclusive at the time of informed consenting); Participants must be in good general health, with no significant medical history, and have no clinically significant abnormalities on physical examination at Screening and/or before administration of study drug; Stable body weight for at least 3 months prior to Screening (i.e., <5% change) by self-declaration; Exclusion Criteria: Prior or ongoing medical conditions, medical history, physical findings, or laboratory abnormality that, in the Investigator's (or delegate's) opinion, may require treatment or render the participant unlikely to fully complete the study, or any condition that presents undue risk from the investigational product (IP) or procedures or interfere with study assessments; Confirmed diagnosis of diabetes mellitus type 1, type 2, or of any other forms at any time, and/or occurrence of documented or suspected hypoglycaemic episodes within 12 months prior to Screening; Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Parallel Assignment
Interventional Model Description: This is a single centre, double-blind, randomised, multiple-dose, placebo-controlled study, including four cohorts (Cohorts 1, 2, 3, and 4) .
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Cohort 1 will enroll 10 healthy participants, doses ranging from 2mg to 7mg. | Drug: XW004<br>* 2, 7, 15, 30mg tablets once daily for 15 days.<br>* Other names: GLP-1 analogue;|
| Experimental: Cohort 2<br>Cohort 2 will enroll 10 healthy participants, doses ranging from 2mg to 15mg. | Drug: XW004<br>* 2, 7, 15, 30mg tablets once daily for 15 days.<br>* Other names: GLP-1 analogue;|
| Experimental: Cohort 3<br>Cohort 3 will enroll 10 healthy participants, doses ranging from 7mg to 30mg. | Drug: XW004<br>* 2, 7, 15, 30mg tablets once daily for 15 days.<br>* Other names: GLP-1 analogue;|
| Experimental: Cohort 4<br>Cohort 4 will enroll 10 otherwise 'healthy' participants with obesity, doses ranging from 7mg to 30mg. | Drug: XW004<br>* 2, 7, 15, 30mg tablets once daily for 15 days.<br>* Other names: GLP-1 analogue;|
| Experimental: T2026 tablet<br>Tablet containing no ecnoglutide but T2026 2 participants receiving T2026 tablet will be enrolled in each cohort. | Drug: T2026<br>* Once daily for 15 days.<br>* Other names: Absorption enhancer;|
| Placebo Comparator: Placebo tablet<br>placebo containing no ecnoglutide or T2026 2 participants receiving placebo tablet will be enrolled in each cohort. | Drug: Placebo<br>* Once daily for 15 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment emergent adverse events (TEAEs) | Count of adverse events | 36 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed drug concentration | Calculated based on XW003 measured in blood. | 36 days | 
| Time of the maximum drug concentration | Calculated based on XW003 measured in blood | 36 days | 
| Maximum plasma concentration after last dosing | Calculated based on XW003 measured in blood | 36 days | 
| Change from Baseline in body weight | Percentage of body weight loss | 36 days | 
| Change from Baseline in fasting plasma glucose | Percentage of fasting plasma glucose change | 36 days | 
| Maximum observed drug concentration T2026 | Calculated based on T2026 measured in blood. | 36 days | 
| Time of the maximum drug concentration T2026 | Calculated based on T2026 measured in blood. | 36 days | 
| Maximum plasma concentration after last dosing T2026 | Calculated based on T2026 measured in blood. | 36 days | 
| Incidence of anti-XW004 antibodies at end of study | Count of episodes | 36 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Type 2 Diabetes Mellitus