A Phase 1 Study of HEC88473 Injection in Healthy Subjects, Obese Subjects and T2DM Subjects
Phase 1
Completed
- Conditions
- T2DM (Type 2 Diabetes Mellitus)ObesityHealthy Subjects
- Interventions
- Drug: HEC88473 injectionDrug: Placebo
- Registration Number
- NCT05943886
- Lead Sponsor
- Dongguan HEC Biopharmaceutical R&D Co., Ltd.
- Brief Summary
This is a single-center, randomized, double-blind, placebo-controlled, escalating single-dose and multiple-dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of HEC88473 injection in healthy subjects, obese subjects and subjects with type 2 diabetes mellitus (T2DM).
- Detailed Description
This study is divided into two parts, Part A is an escalating single-dose study in healthy subjects and obese subjects, and Part B is an escalating multiple-dose study in subjects with T2DM.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 164
Inclusion Criteria
Part A
- Males or females, between 18 and 45 years of age, inclusive, at screening.
- Body weight ≥ 50 kg for males and body weight ≥ 45 kg for females. 18≤body mass index (BMI)<28 kg/m2 for nonobese subjects and 28≤BMI≤45 kg/m2 for obese subjects.
Part B
- Males or females, between 18 and 65 years of age, inclusive, at screening.
- 24 kg/m2≤BMI≤35 kg/m2.
- Subjects diagnosed with T2DM, newly diagnosed subjects at screening, or treated with diet and exercise alone within 3 months before screening and still have poor blood glucose control, or treated with a stable dose of metformin for ≥ 3 months before screening.
- 7.0%≤ HbA1c ≤10.5% at screening.
Exclusion Criteria
Part A
- Smoked more than 5 cigarettes per day within 3 months before the study.
- Immunization with a live attenuated vaccine or coronavirus vaccination within 1 month prior to screening or planned vaccination during the course of the study.
- Positive alcohol breath test result or positive urine drug screen.
- Blood donation (> 300 mL) or massive blood loss (> 400 mL) within 3 months before screening.
Part B
- Have type 1 diabetes mellitus.
- Have had ≥1 episode of severe hypoglycemia within 6 months before screening, or history of recurrent hypoglycemia (history of hypoglycemia more than 3 times in 3 months).
- Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level >5 times the upper limit of the reference range at screening.
- Have serum calcitonin ≥20 ng/L at screening.
- Have a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2; or have hereditary diseases that can easily induce MTC.
- Fasted triglycerides > 5.7 mmol/L at screening. If the patient is on lipid-lowering therapies, doses must be stable for 30 days prior to screening.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Single dose of 0.5 mg HEC88473 HEC88473 injection Healthy subjects, receiving a single dose of 0.5 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 5.1 mg HEC88473 HEC88473 injection Healthy subjects, receiving a single dose of 5.1 mg HEC88473 (N=8) or placebo(N=2) after meal. Obese subjects, receiving a single dose of 5.1 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 10.2 mg HEC88473 HEC88473 injection Healthy subjects, receiving a single dose of 10.2 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 25.5 mg HEC88473 HEC88473 injection Healthy subjects, receiving a single dose of 25.5 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 10.2 mg HEC88473 Placebo Healthy subjects, receiving a single dose of 10.2 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 25.5 mg HEC88473 Placebo Healthy subjects, receiving a single dose of 25.5 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 1.7 mg HEC88473 Placebo Healthy subjects, receiving a single dose of 1.7 mg HEC88473 (N=8) or placebo(N=2) after meal. Multiple doses of 45.9 mg HEC88473 Placebo T2DM subjects, receiving a weekly dose of HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. The 45.9 mg cohort was administered by titration. Single dose of 0.5 mg HEC88473 Placebo Healthy subjects, receiving a single dose of 0.5 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 1.7 mg HEC88473 HEC88473 injection Healthy subjects, receiving a single dose of 1.7 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 17.0 mg HEC88473 Placebo Healthy subjects, receiving a single dose of 17.0 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 81.6 mg HEC88473 HEC88473 injection Healthy subjects, receiving a single dose of 81.6 mg HEC88473 (N=8) or placebo(N=2) after meal. Multiple doses of 5.1 mg HEC88473 HEC88473 injection T2DM subjects, receiving a weekly dose of 5.1 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. Multiple doses of 30.6 mg HEC88473 HEC88473 injection T2DM subjects, receiving a weekly dose of HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. The 30.6 mg cohort was administered by titration. Multiple doses of 30.6 mg HEC88473 Placebo T2DM subjects, receiving a weekly dose of HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. The 30.6 mg cohort was administered by titration. Single dose of 5.1 mg HEC88473 Placebo Healthy subjects, receiving a single dose of 5.1 mg HEC88473 (N=8) or placebo(N=2) after meal. Obese subjects, receiving a single dose of 5.1 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 35.7 mg HEC88473 HEC88473 injection Healthy subjects, receiving a single dose of 35.7 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 47.6 mg HEC88473 HEC88473 injection Healthy subjects, receiving a single dose of 47.6 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 47.6 mg HEC88473 Placebo Healthy subjects, receiving a single dose of 47.6 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 62.9 mg HEC88473 Placebo Healthy subjects, receiving a single dose of 62.9 mg HEC88473 (N=8) or placebo(N=2) after meal. Multiple doses of 5.1 mg HEC88473 Placebo T2DM subjects, receiving a weekly dose of 5.1 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. Multiple doses of 15.3 mg HEC88473 Placebo T2DM subjects, receiving a weekly dose of 15.3 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. Single dose of 17.0 mg HEC88473 HEC88473 injection Healthy subjects, receiving a single dose of 17.0 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 35.7 mg HEC88473 Placebo Healthy subjects, receiving a single dose of 35.7 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 62.9 mg HEC88473 HEC88473 injection Healthy subjects, receiving a single dose of 62.9 mg HEC88473 (N=8) or placebo(N=2) after meal. Single dose of 81.6 mg HEC88473 Placebo Healthy subjects, receiving a single dose of 81.6 mg HEC88473 (N=8) or placebo(N=2) after meal. Multiple doses of 15.3 mg HEC88473 HEC88473 injection T2DM subjects, receiving a weekly dose of 15.3 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. Multiple doses of 45.9 mg HEC88473 HEC88473 injection T2DM subjects, receiving a weekly dose of HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. The 45.9 mg cohort was administered by titration. Multiple doses of 68.0 mg HEC88473 HEC88473 injection T2DM subjects, receiving a weekly dose of HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. The 68.0 mg cohort was administered by titration. Multiple doses of 68.0 mg HEC88473 Placebo T2DM subjects, receiving a weekly dose of HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. The 68.0 mg cohort was administered by titration.
- Primary Outcome Measures
Name Time Method Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) after a single dose of HEC88473 Baseline to day 15 Adverse Events (AEs)
AUC Predose and postdose 4、8、10、12、14、24、48、72、96、168、216、336 hours Area under the serum concentration-time curve (AUC)
Cmax Predose and postdose 4、8、10、12、14、24、48、72、96、168、216、336 hours Maximum observed serum concentration of HEC88473
Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) after multiple dose of HEC88473 Baseline to day 43 Adverse Events (AEs)
- Secondary Outcome Measures
Name Time Method Change from baseline of Adiponectin at day 38 Baseline to day 38 Adiponectin
OGTT Day-1, Day3 and Day 7 Oral glucose tolerance test
Assessment of the incidence of anti drug antibodies (ADA) developed against HEC88473 after dosing Baseline to day 43 anti drug antibodies (ADA)
Fasting lipid concentration Baseline to day 43 Fasting lipid concentration
Change from baseline of HbA1c at day 38 Baseline to day 38 HbA1c
Trial Locations
- Locations (1)
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China