This is a Phase 1, randomized, double-blind (with open-label sentinel cohorts), placebo-controlled, single-ascending-dose study designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of MI226 Injection in participants with abdominal fat accumulation.
The study will enroll approximately 52 participants across 8 dose cohorts (24 mg to 1200 mg). The first two cohorts (24 mg and 60 mg) are open-label sentinel groups (2 participants each, all receiving active drug). Cohorts 3-8 are double-blind with a 6:1 or 8:1 randomization ratio to MI226 Injection or placebo. Each participant receives a single subcutaneous abdominal injection (0.2 mL per injection point, 1 cm apart, total volume up to 20 mL). The primary objectives are to assess the safety/tolerability and PK profile of MI226. Secondary objective is to evaluate the effect of MI226 on QT/QTc interval using a concentration-QTc (C-QTc) model in cohorts 5-8. Participants are followed for 28 days post-dose with serial safety assessments, PK blood sampling (13 time points over 24 hours for cohorts 3-8), and ECG monitoring. Dose escalation proceeds after review of 7-day safety data from the preceding cohort, with predefined stopping criteria.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
52
Single injection into the subcutaneous adipose tissue.
Single injection into the subcutaneous adipose tissue.
Single injection into the subcutaneous adipose tissue.
Peking Union Medical College Hospital
Beijing, Beijing Municipality, China
RECRUITINGIncidence and severity of treatment-emergent adverse events (TEAEs) as assessed by NCI CTCAE v6.0
Safety and tolerability will be evaluated by recording adverse events. AEs will be graded according to NCI CTCAE v6.0.
Time frame: Up to Day 28
Number of participants with clinically significant abnormal physical examination findings
Physical examination includes general appearance, skin, head and neck (eyes, ears, nose, throat), chest and lungs, cardiovascular system, abdomen, extremities, and neurological system. Clinically significant abnormalities will be recorded and summarized by system organ class.
Time frame: Up to Day 28
Number of participants with clinically significant changes in vital signs
Vital signs include systolic blood pressure (mmHg), diastolic blood pressure (mmHg), pulse rate (bpm), respiratory rate (breaths/min), and body temperature (°C). Clinically significant abnormalities in any of these parameters will be counted as an event.
Time frame: Up to Day 28
Number of participants with clinically significant abnormal laboratory test results
Laboratory examinations include hematology, serum chemistry, and urinalysis. Abnormalities will be graded according to CTCAE v6.0, and the number of participants with Grade ≥ 1 or clinically significant shifts from baseline will be summarized.
Time frame: Up to Day 7
Number of participants with clinically significant abnormal 12-lead electrocardiogram (ECG) findings
ECG parameters include heart rate (bpm), PR interval (msec), QRS duration (msec), and QT interval (msec). Clinically significant abnormalities will be recorded.
Time frame: Up to Day 7
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Single injection into the subcutaneous adipose tissue.
Single injection into the subcutaneous adipose tissue.
Single injection into the subcutaneous adipose tissue.
Single injection into the subcutaneous adipose tissue.
Single injection into the subcutaneous adipose tissue.
Placebo
Maximum observed plasma concentration (Cmax) of MI226
Plasma concentrations of MI226 will be measured using a validated LC-MS/MS method. Cmax will be derived using non-compartmental analysis.
Time frame: From pre-dose to 24 hours post-dose
Time to reach maximum observed plasma concentration (Tmax) of MI226
Plasma concentrations of MI226 will be measured using a validated LC-MS/MS method.
Time frame: From pre-dose to 24 hours post-dose
Terminal elimination half-life (t1/2) of MI226
Plasma concentrations of MI226 will be measured using a validated LC-MS/MS method.
Time frame: From pre-dose to 24 hours post-dose
Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of MI226
Plasma concentrations of MI226 will be measured using a validated LC-MS/MS method. AUC0-inf will be derived using non-compartmental analysis.
Time frame: From pre-dose to 24 hours post-dose