Healthy Subjects, Obesity, T2DM (Type 2 Diabetes Mellitus)
Conditions
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.
Interventions
HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.
DRUGPlacebo
Placebo will be administered by subcutaneous injection in the abdomen.
Sponsors
Dongguan HEC Biopharmaceutical R&D Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Part A 1. Males or females, between 18 and 45 years of age, inclusive, at screening. 2. 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 1. Males or females, between 18 and 65 years of age, inclusive, at screening. 2. 24 kg/m2≤BMI≤35 kg/m2. 3. 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. 4. 7.0%≤ HbA1c ≤10.5% at screening.
Exclusion criteria
Part A 1. Smoked more than 5 cigarettes per day within 3 months before the study. 2. Immunization with a live attenuated vaccine or coronavirus vaccination within 1 month prior to screening or planned vaccination during the course of the study. 3. Positive alcohol breath test result or positive urine drug screen. 4. Blood donation (\> 300 mL) or massive blood loss (\> 400 mL) within 3 months before screening. Part B 1. Have type 1 diabetes mellitus. 2. 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). 3. 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. 4. Have serum calcitonin ≥20 ng/L at screening. 5. 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. 6. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) after multiple dose of HEC88473 | Baseline to day 43 | Adverse Events (AEs) |
| Cmax | Predose and postdose 4、8、10、12、14、24、48、72、96、168、216、336 hours | Maximum observed serum concentration of HEC88473 |
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Change from baseline of Adiponectin at day 38 | Baseline to day 38 | Adiponectin |
| Fasting lipid concentration | Baseline to day 43 | Fasting lipid concentration |
| Change from baseline of HbA1c at day 38 | Baseline to day 38 | HbA1c |
Countries
China
Outcome results
None listed