Phase I Study of XTL6001 Injection in Healthy and Obese Subjects

Official title

A Randomized, Double-blind, Placebo-controlled Phase I Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Administration of XTL6001 Injection in Healthy and Obese Subjects

Overview

This is a multicenter, randomized, double-blind, placebo-controlled Phase I study to evaluate safety, PK and PD of single ascending dose (SAD) and multiple ascending dose (MAD) of XTL6001 injection in healthy and obese adult subjects. SAD study: Includes 5 dose cohorts, with 40 subjects planned for enrollment. MAD study Includes 2 dose cohorts, with 30 subjects planned for enrollment.

Interventions

• Drug XTL6001
  XTL6001 is a triple-target Glucagon-like peptide-1 receptor （GLP-1R） relevant agonist, intending to manage overweight/obesity and other metabolic diseases
• Drug Placebo
  This intervention contains no active ingredients

Primary outcome measures

• Incidence and severity of AEs (Adverse Events) and SAEs (Serious Adverse Events) [Time frame: SAD: up to Day 8 MAD: up to Day 57]

Secondary outcome measures (12)

• The maximum plasma concentration (Cmax) of XTL6001 [Time frame: Within 1 hour before each weekly dosing, and at 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours after the first and last dose administration of the target dose level.]
• Tmax of XTL6001 [Time frame: Within 1 hour before each weekly dosing, and at 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours after the first and last dose administration of the target dose level.]
• Elimination half-life (T1/2) of XTL6001 [Time frame: Within 1 hour before each weekly dosing, and at 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours after the first and last dose administration of the target dose level.]
• Area under the plasma concentration-time curve during one dosing interval (AUC) 0-tau of XTL6001 [Time frame: Within 1 hour before each weekly dosing, and at 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours after the first and last dose administration of the target dose level.]
• AUC0-t of XTL6001 [Time frame: Within 1 hour before each weekly dosing, and at 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours after the first and last dose administration of the target dose level.]
• Body weight [Time frame: MAD: up to Day57]
• Body mass index （BMI） [Time frame: MAD: up to Day57]
• Waist circumference [Time frame: MAD: up to Day57]
• Waist-to-hip ratio [Time frame: MAD: up to Day57]
• Blood lipids [Time frame: MAD: up to Day57]
• Blood glucose [Time frame: MAD: up to Day57]
• Insulin [Time frame: MAD: up to Day57]

Eligibility criteria

Inclusion criteria

Inclusion Criteria for Subjects in SAD part:

• Age ≥ 18 and < 65 years at screening.
• Body mass index (BMI) ≥ 18.5 kg/m² and < 28.0 kg/m² at screening.
• Body weight ≥ 50.0 kg for males and ≥ 45.0 kg for females at screening.
• Signed informed consent form prior to the trial, with full understanding of the study objectives, procedures, and potential adverse reactions.

Inclusion Criteria for Subjects in MAD part:

• Age ≥ 18 and < 65 years at screening.
• BMI ≥ 18.5 kg/m2且 < 40.0kg/m².
• Body weight ≥ 50.0 kg for males and ≥ 45.0 kg for females at screening.
• Stable body weight (fluctuation < 5%) for at least 3 months prior to screening.
• Signed informed consent form prior to the trial, with full understanding of the study objectives, procedures, and potential adverse reactions.

Exclusion criteria

Exclusion Criteria for Subjects in SAD part:

• History of type 1 or type 2 diabetes mellitus, or HbA1c > 6.5% or fasting plasma glucose > 7.0 mmol/L at screening.
• Clinically significant gastric emptying disorders, chronic use of medications directly affecting gastrointestinal motility, severe chronic gastrointestinal diseases, or prior gastrointestinal surgery.
• History of acute or chronic pancreatitis.
• Symptomatic gallbladder disease.
• Malignancy within 5 years prior to screening (except adequately treated non-melanoma skin cancer).
• Personal/family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2A/2B (MEN 2A/2B).
• Female subjects with positive pregnancy test or lactation.

Exclusion Criteria for Subjects in MAD part:

• History of type 1 or type 2 diabetes mellitus, or HbA1c > 6.5% or fasting plasma glucose > 7.0 mmol/L at screening.
• UnderlyingCushing's syndrome, hypothyroidism, PCOS,.
• Clinically significant gastric emptying disorders, chronic use of medications directly affecting gastrointestinal motility, severe chronic gastrointestinal diseases, or gastrointestinal surgeries that may compromise safety or data interpretation.
• History of acute or chronic pancreatitis.
• Symptomatic gallbladder disease.
• Malignancy within 5 years prior to screening (except adequately treated non-melanoma skin cancer).
• Personal/family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2A/2B (MEN 2A/2B).
• Female subjects with positive pregnancy test or lactation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Sequential

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Shijitan Hospital, Capital Medical University — Beijing

Identifiers

NCT: NCT07205432 · XTL6001-I-C01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗