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This study is a first-in-human clinical trial of CMS-D008 conducted in Chinese healthy and overweight or obese adult participants, consisting of three parts: Part-1 Single Ascending Dose (SAD) study (hereinafter referred to as Part-1 SAD study), Part-2 Multiple Ascending Dose (MAD) study (hereinafter referred to as Part-2 MAD study), and Part-3 expansion study. The study aims to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) characteristics, and immunogenicity of single and multiple subcutaneous injections of CMS-D008 injection in Chinese healthy and overweight or obese adult participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SAD:CMS-D008 | Experimental | 5 sequential dose escalation cohorts - participants are randomized either to investigational drug or matching placebo |
|
| SAD: Placebo | Placebo Comparator | 5 sequential dose escalation cohorts - participants are randomized either to investigational drug or matching placebo |
|
| MAD: CMS-D008 | Experimental | 3 sequential dose escalation cohorts - participants are randomized either to investigational drug or matching placebo |
|
| MAD: Placebo | Placebo Comparator | 3 sequential dose escalation cohorts - participants are randomized either to investigational drug or matching placebo |
|
| Expansion study: CMS-D008 | Experimental | 2 sequential dose escalation cohorts - participants are randomized either to investigational drug or matching placebo |
|
| Expansion study: Placebo |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CMS-D008 | Biological | Healthy and overweight or obese participants |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline to each visit point in vital signs (temperature, blood pressure, heart rate, respiratory rate) | Measured using electronic sphygmomanometer/thermometer according to standard procedures, record actual values at each visit point, and assess abnormal values. | through study completion,an average of 0.6 years |
| Incidence rate of abnormal findings in comprehensive systemic physical examination | Record abnormal physical examination findings by system (cardiovascular, respiratory, digestive, etc.), summarize the number and incidence rate of abnormalities in each system, and categorize them as related or unrelated to the study drug. | through study completion,an average of 0.6 years |
| Hematology, biochemistry, and urinalysis laboratory test indicators | The tests include complete blood count (WBC, RBC, Hb, etc.), blood biochemistry (ALT, AST, Cr, etc.), and urinalysis; changes from baseline were calculated, and the incidence of abnormal values was summarized according to CTCAE 6.0 grading. | through study completion,an average of 0.6 years |
| 12-lead electrocardiogram QTc interval, heart rate, and incidence of morphological abnormalities | Collected using standard 12-lead ECG equipment, interpreted by a central laboratory, with the number and incidence rate of QTc interval changes, heart rate abnormalities, and morphological abnormalities (such as premature beats, ST-T changes) summarized. | through study completion,an average of 0.6 years |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum plasma drug concentration (Cmax) | Calculate the maximum observed plasma concentration from the plasma drug concentration-time curve after administration using non-compartmental analysis (NCA), unit: ng/mL | Through 48 hours post-dose |
| Tmax |
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Inclusion Criteria:
Exclusion Criteria:
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| ID | Term |
|---|---|
| D050177 | Overweight |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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| Placebo Comparator |
2 sequential dose escalation cohorts - participants are randomized either to investigational drug or matching placebo |
|
| Placebo | Drug | Healthy and overweight or obese participants |
|
Using non-compartmental analysis (NCA) to calculate the time to reach Cmax after drug administration, unit: h
| Through 48 hours post-dose |
| Area under the curve (AUC0-t) | Calculate the area under the concentration-time curve from time of administration (0 h) to the last quantifiable concentration time point (t) using non-compartmental analysis (NCA), unit: ng·h/mL | Through 48 hours post-dose |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |