A Phase 1 Study of HEC88473 Injection in Healthy Subjects, Obese Subjects and T2DM Subjects

Dongguan HEC Biopharmaceutical

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects; Obesity; T2DM (Type 2 Diabetes Mellitus)

Treatments: Drug: Placebo; Drug: HEC88473 injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT05943886

HEC88473-DM-101

Details and patient eligibility

About

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).

Full 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.

Enrollment: 164 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

---

164 participants in 15 patient groups

Single dose of 0.5 mg HEC88473

Experimental group

Description:

Healthy subjects, receiving a single dose of 0.5 mg HEC88473 (N=8) or placebo(N=2) after meal.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Single dose of 1.7 mg HEC88473

Experimental group

Description:

Healthy subjects, receiving a single dose of 1.7 mg HEC88473 (N=8) or placebo(N=2) after meal.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Single dose of 5.1 mg HEC88473

Experimental group

Description:

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.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Single dose of 10.2 mg HEC88473

Experimental group

Description:

Healthy subjects, receiving a single dose of 10.2 mg HEC88473 (N=8) or placebo(N=2) after meal.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Single dose of 17.0 mg HEC88473

Experimental group

Description:

Healthy subjects, receiving a single dose of 17.0 mg HEC88473 (N=8) or placebo(N=2) after meal.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Single dose of 25.5 mg HEC88473

Experimental group

Description:

Healthy subjects, receiving a single dose of 25.5 mg HEC88473 (N=8) or placebo(N=2) after meal.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Single dose of 35.7 mg HEC88473

Experimental group

Description:

Healthy subjects, receiving a single dose of 35.7 mg HEC88473 (N=8) or placebo(N=2) after meal.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Single dose of 47.6 mg HEC88473

Experimental group

Description:

Healthy subjects, receiving a single dose of 47.6 mg HEC88473 (N=8) or placebo(N=2) after meal.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Single dose of 62.9 mg HEC88473

Experimental group

Description:

Healthy subjects, receiving a single dose of 62.9 mg HEC88473 (N=8) or placebo(N=2) after meal.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Single dose of 81.6 mg HEC88473

Experimental group

Description:

Healthy subjects, receiving a single dose of 81.6 mg HEC88473 (N=8) or placebo(N=2) after meal.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Multiple doses of 5.1 mg HEC88473

Experimental group

Description:

T2DM subjects, receiving a weekly dose of 5.1 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Multiple doses of 15.3 mg HEC88473

Experimental group

Description:

T2DM subjects, receiving a weekly dose of 15.3 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Multiple doses of 30.6 mg HEC88473

Experimental group

Description:

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.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Multiple doses of 45.9 mg HEC88473

Experimental group

Description:

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.

Treatment:

Drug: HEC88473 injection

Drug: Placebo

Multiple doses of 68.0 mg HEC88473

Experimental group

Description:

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.

Treatment:

Drug: HEC88473 injection

Drug: Placebo