Dose-escalation and Food Effect Study of ZT006 in Healthy, Overweight and Obese Participants

A Randomized, Double-blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ZT006 as Well as the Food Effect on the Pharmacokinetics of ZT006 in Healthy, Overweight and Obese Participants

ZT006 is an oral, long-acting glucagon-like peptide-1. This first-in-human study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ZT006 in healthy, overweight and obese participants. The study comprises three parts, i.e. single dose-escalation, multiple dose-escalation, food effect on the pharmacokinetics of ZT006.

In the single dose-escalation study, participants will receive a single dose (ZT006 dose level 1 - 5 or corresponding placebo) of ZT006 under fasted condition. A higher dose can only be given after obtaining acceptable safety and tolerability data for at least 7 days after the previous dose. After study drug administration, there will be a 7-day in-house period for safety observation and pharmacokinetics samples collection. Participants will join ambulatory visits until 42 days post-dose.

In the multiple dose-escalation study, participants will receive a daily dose of ZT006 or corresponding placebo over 42 days in a dose up-titration fashion according to the following regimen:

• Cohort 1: dose level 1 - dose level 2 - dose level 3
• Cohort 2: dose level 1 - dose level 2 - dose level 3 - dose level 4
• Cohort 3: dose level 2 - dose level 3 - dose level 4
• Cohort 4: dose level 2 - dose level 3 - dose level 4 - dose level 5

Dosing of a cohort with higher drug exposure can only be done after evaluation of safety and tolerability data for at least 14 days after the first dose in the previous cohort. Participants will join ambulatory visits until 35 days after the last dose.

To evaluate the food effect on the pharmacokinetics of ZT006, participants who have received single dose of ZT006 or placebo of dose level 4 in the single dose-escalation study will receive another dose of ZT006 or placebo after a high fat, high caloric breakfast.

Study Overview

• Status: Completed
• Conditions: Overweight,Obesity
• Intervention / Treatment: Drug: ZT006; Drug: ZT006; Drug: ZT006; Drug: ZT006; Drug: ZT006; Drug: ZT006; Drug: ZT006; Drug: ZT006; Drug: ZT006; Drug: Placebo of ZT006; Drug: Placebo of ZT006; Drug: Placebo of ZT006

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Affiliated Hospital of Anhui Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, 12-lead electrocardiogram and clinical laboratory tests (hematology, urinalysis, chemistry, coagulation), as judged by the investigator.
• Male or female, age between 18 - 55 years (both inclusive) at the time of signing of the informed consent.
• Body mass index (BMI) 19.0 - 35.0 kg/m²(both inclusive). Body weight >50.0 kg for male participants and >45.0 kg for female participants. BMI 19 - 28.0 kg/m²(both inclusive) for single-dose escalation study, BMI 19.0 - 28.0 kg/m²(both inclusive) for cohorts 1 and 2 of multiple-dose escalation study, BMI 24.0 - 35.0 kg/m²(both inclusive) for cohorts 3 and 4 of multiple-dose escalation study.
• Having dietary caloric restriction and increased physical activity for ≥3 months, with change in body weight (increase or decrease) no more than 5%, irrespective of medical records.

Exclusion Criteria:

• Known hypersensitivity to the study drug or excipients or GLP-1 receptor agonists.
• Medical history of hypoglycemia.
• History or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2, or history of pancreatitis or symptomatic gallbladder disease.
• Previous diagnosis of endocrine disorders or monogenic mutations causing obesity, including but not limited to hypothalamic obesity, pituitary obesity, hypothyroidism-induced obesity, Cushing's syndrome, insulinoma, acromegaly, or hypogonadism.
• Use of GLP-1 receptor agonists within 30 days or 5 half-lives (whichever is longer) before the first dose of the investigational intervention.
• Glycated hemoglobin (HbA1c) > 6.0% or fasting plasma glucose < 3.9 mmol/L or > 6.1 mmol/L at screening, or diagnosed with diabetes mellitus of type 1 or type 2 diabetes or other specific types derived from other causes.
• Aspartate aminotransferase ≥ 2 × upper limit of normal (ULN), Alanine aminotransferase ≥ 2 × ULN, or total bilirubin ≥ 1.5 × ULN
• Calcitonin above ULN at screening.
• Other clinically significant diseases detected within 12 months before screening (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, oncological, pulmonary, immunological, psychiatric, or cardiovascular diseases).
• Use of prescription drugs (excluding topical eye/nose drops and creams without systemic exposure risk), over-the-counter drugs, dietary supplements, vitamins, or herbal medicines (excluding routine vitamins) within 2 weeks before screening.
• Long-term use of medications directly affecting gastrointestinal motility prior to screening. Use of weight-loss medications (including but not limited to orlistat) within 3 months before dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZT006 tablet, dose level 1, single dose, fasted	Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 1 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 2 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 3 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 4 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 5 under fasted condition.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 14 days, then dose level 4 for 14 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 14 days, then dose level 5 for 14 days.
Experimental: ZT006 tablet, dose level 2, single dose, fasted	Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 1 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 2 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 3 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 4 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 5 under fasted condition.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 14 days, then dose level 4 for 14 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 14 days, then dose level 5 for 14 days.
Experimental: ZT006 tablet, dose level 3, single dose, fasted	Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 1 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 2 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 3 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 4 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 5 under fasted condition.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 14 days, then dose level 4 for 14 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 14 days, then dose level 5 for 14 days.
Experimental: ZT006 tablet, dose level 4, single dose, fasted and fed	Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 1 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 2 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 3 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 4 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 5 under fasted condition.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 14 days, then dose level 4 for 14 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 14 days, then dose level 5 for 14 days.
Experimental: ZT006 tablet, dose level 5, single dose, fasted	Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 1 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 2 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 3 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 4 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 5 under fasted condition.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 14 days, then dose level 4 for 14 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 14 days, then dose level 5 for 14 days.
Experimental: ZT006 tablet, multiple doses, cohort 1	Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 1 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 2 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 3 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 4 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 5 under fasted condition.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 14 days, then dose level 4 for 14 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 14 days, then dose level 5 for 14 days.
Experimental: ZT006 tablet, multiple doses, cohort 2	Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 1 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 2 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 3 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 4 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 5 under fasted condition.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 14 days, then dose level 4 for 14 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 14 days, then dose level 5 for 14 days.
Experimental: ZT006 tablet, multiple doses, cohort 3	Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 1 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 2 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 3 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 4 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 5 under fasted condition.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 14 days, then dose level 4 for 14 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 14 days, then dose level 5 for 14 days.
Experimental: ZT006 tablet, multiple doses, cohort 4	Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 1 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 2 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 3 under fasted condition.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 4 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.; Drug: ZT006; Participants will receive a single dose of ZT006 of dose level 5 under fasted condition.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 14 days, then dose level 4 for 14 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 28 days.; Drug: ZT006; Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 14 days, then dose level 5 for 14 days.
Placebo Comparator: placebo of ZT006, single dose, fasted	Drug: Placebo of ZT006; Participants will receive a single dose of placebo of ZT006 under fasted condition.; Drug: Placebo of ZT006; Participants will receive a single dose of placebo of ZT006 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.; Drug: Placebo of ZT006; Participants will receive daily doses of placebo of ZT006 for 42 days.
Placebo Comparator: placebo of ZT006, single dose, fasted and fed	Drug: Placebo of ZT006; Participants will receive a single dose of placebo of ZT006 under fasted condition.; Drug: Placebo of ZT006; Participants will receive a single dose of placebo of ZT006 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.; Drug: Placebo of ZT006; Participants will receive daily doses of placebo of ZT006 for 42 days.
Placebo Comparator: placebo of ZT006, multiple doses	Drug: Placebo of ZT006; Participants will receive a single dose of placebo of ZT006 under fasted condition.; Drug: Placebo of ZT006; Participants will receive a single dose of placebo of ZT006 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.; Drug: Placebo of ZT006; Participants will receive daily doses of placebo of ZT006 for 42 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of treatment-emergent adverse events after single dose administration under fasted condition.	Summarized from adverse event reporting in %	From baseline to Day 43
Rate of treatment-emergent adverse events during and after multiple-dose administration.	Summarized from adverse event reporting in %	From baseline to end of study (Day 77)
Rate of treatment-emergent adverse events after single dose administration under fed condition.	Summarized from adverse event reporting in %	From Day 44 to end of study (Day 86)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration-time curve from time zero to infinity after single-dose administration under fasted condition.	Measured in ng*h/mL	From baseline to Day 43
Maximal observed concentration after single-dose administration under fasted condition.	Measured in ng/mL	From baseline to Day 43
Time to reach the maximal observed concentration after single-dose administration under fasted condition.	Measured in hours	From baseline to Day 43
Terminal half-life after single-dose administration under fasted condition.	Measured in hours	From baseline to Day 43
Area under the concentration-time curve during the dosing interval at steady state.	Measured in ng*h/mL	Day 42 to Day 77
Maximal observed concentration at steady state.	Measured in ng/mL	Day 42 to Day 77
Time to reach the maximal observed concentration at steady state.	Measured in hours	From Day 42 to Day 77
Terminal half-life at steady state.	Measured in hours	From Day 42 to Day 77
Area under the concentration-time curve from time zero to infinity after single-dose administration under fed condition.	Measured in ng*h/mL	From Day 44 to end of study (Day 86)
Maximal observed concentration after single-dose administration under fed condition.	Measured in ng/mL	From Day 44 to end of study (Day 86)
Time to reach the maximal observed concentration after single-dose administration under fed condition.	Measured in hours	From Day 44 to end of study (Day 86)
Terminal half-life after single-dose administration under fed condition.	Measured in hours	From Day 44 to end of study (Day 86)
Incidence of ZT006 anti-drug antibody after single-dose administration under fasted condition.	Measured in %	From baseline to Day 43
Incidence of ZT006 anti-drug antibody during and after multiple-dose administration.	Measured in %	From baseline to end of study (Day 77)

Collaborators and Investigators

• Sponsor: Beijing QL Biopharmaceutical Co.,Ltd
• Investigators: Principal Investigator: Wei Hu, MD, The Second Hospital of Anhui Medical University; Principal Investigator: Yijun Du, Master, The Second Hospital of Anhui Medical University

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2024
• Primary Completion (Actual): June 14, 2025
• Study Completion (Actual): June 24, 2025

Study Registration Dates

• First Submitted: December 15, 2025
• First Submitted That Met QC Criteria: December 15, 2025
• First Posted (Actual): December 29, 2025

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity
• Other Study ID Numbers: BJQL-ZT006-1001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No