Study on the Mass Balance of [14C] CMS-D002 in Healthy Adult Participants in China

Study on the Mass Balance of [14C] CMS-D002 in Healthy Adult Participants in China

This phase 1, single-group study will evaluate the mass balance of [14C] CMS-D002 after a single oral dose in healthy adult participants in China. The study will assess total radioactivity recovery and routes of excretion, characterize whole-blood and plasma pharmacokinetics, and determine metabolite profiles and major biotransformation pathways.

Inclusion Criteria:

1. Participants must be fully informed about the trial prior to participation, understand the trial content, procedures, and possible adverse events related to the investigational drug, and voluntarily sign a written informed consent form;
2. Chinese adult participants aged 18-45 years (inclusive);
3. At screening, male participants weigh no less than 50 kg, female participants weigh no less than 45 kg, and body mass index [BMI = weight (kg) / height² (m²)] ranges from 19.0-26.0 kg/m² (inclusive);
4. Female participants have a regular menstrual history, with at least two consecutive regular menstrual cycles (21-35 days, inclusive) in the most recent period prior to screening, and no abnormal uterine bleeding;
5. Participants of childbearing potential voluntarily adopt highly effective contraception from signing informed consent until 6 months after trial completion (see Appendix I for details; female participants prohibited from using oral contraceptives during the study), and have no plans for oocyte or sperm cryopreservation or donation during this period.

Exclusion Criteria:

1. Investigator determines the presence of other clinically significant diseases or medical histories that may prevent participants from following the research protocol and completing this study, including but not limited to abnormalities in the central nervous system, cardiovascular system, digestive system, respiratory system, urinary system, hematological system, immune system, psychiatric system, endocrine and metabolic system, etc.;
2. Currently or previously diagnosed with osteoporosis or other metabolic bone diseases;
3. Severe infectious diseases (requiring hospitalization, parenteral antibiotic treatment, or opportunistic infections) within 6 months prior to screening, or history of chronic or recurrent infectious diseases;
4. History of infection and/or fever within 7 days prior to screening;
5. Abnormalities in vital signs examination, physical examination, routine laboratory tests (blood routine, urine routine, stool routine + occult blood, blood biochemistry, coagulation function), chest X-ray (upright), abdominal B-ultrasound, sex hormone tests, breast, uterus and adnexa B-ultrasound (females), reproductive system and urinary system color Doppler ultrasound (males), etc., at screening or baseline, deemed clinically significant by the investigator; or alanine aminotransferase or aspartate aminotransferase exceeding 1.2 times the upper limit of normal (ULN) at screening or baseline;
6. 12-lead ECG at screening or baseline showing: QTcF ≥450 ms (males), QTcF ≥460 ms (females); or other ECG abnormalities deemed clinically significant;
7. Positive results in any of hepatitis B surface antigen quantitative test, hepatitis C antibody test, Treponema pallidum antibody test, or human immunodeficiency virus antigen-antibody test;
8. Any surgical procedures that may affect drug metabolism and excretion (e.g., cholecystectomy, except appendectomy); or planned surgery during the trial period;
9. Hemorrhoids with hematochezia or perianal diseases with periodic/ongoing hematochezia; or severe nausea or vomiting within one week prior to screening; or habitual constipation or diarrhea; or positive fecal occult blood test;
10. Use of any prescription drugs, over-the-counter drugs, Chinese herbal medicines, food supplements (including vitamins, health foods, etc.) within 14 days prior to administration, or presence of other non-drug treatment factors affecting drug absorption, distribution, metabolism, and excretion; use of known CYP3A4 inducers or inhibitors within 1 month prior to baseline (see Appendix II);
11. History of drug allergy or allergic diseases (e.g., asthma, urticaria, eczematous dermatitis, etc.), or deemed possibly or definitely allergic to the investigational drug (including similar drugs) or any of its excipients by the investigator;
12. Received any other investigational drugs or participated in any interventional clinical studies within 3 months or 5 half-lives (whichever is longer) prior to screening;
13. Blood donation or blood loss ≥400 mL within 3 months prior to administration, or blood transfusion or use of blood products within 4 weeks prior to administration;
14. Difficulty in blood collection or intolerance to venipuncture;
15. Workers requiring long-term exposure to radioactive conditions, or significant radioactive exposure within 1 year prior to screening (≥2 chest/abdominal CT scans, or ≥3 other types of X-ray examinations), or participation in radiolabeled drug trials within 1 year prior to screening;
16. History of drug abuse or substance abuse, or positive urine drug abuse screening (morphine, methamphetamine, ketamine, tetrahydrocannabinol acid, methylenedioxymethamphetamine);
17. Average alcohol consumption ≥14 units per week in the 3 months prior to screening (1 unit ≈ 360 mL beer, 45 mL spirits, or 150 mL wine), or positive alcohol breath test;
18. Average daily cigarette smoking >5 cigarettes (or equivalent nicotine products) in the 3 months prior to administration, or unable to abstain from any tobacco products during the trial;
19. Habitual consumption of grapefruit juice or excessive tea, coffee, and/or caffeinated beverages (>8 cups/day, 1 cup = 250 mL), and unable to abstain during the trial; or intake of any chocolate-, caffeine-, or xanthine-rich foods or beverages within 48 hours prior to administration;
20. Vaccination within 4 weeks prior to administration, or planned vaccination within 1 month after administration;
21. Female participants with history of pregnancy, abortion, delivery, or lactation within 6 months prior to screening, or currently pregnant or lactating, or positive serum pregnancy test;
22. Use of oral contraceptives within 30 days prior to screening, or oral contraceptives still within efficacy period at the time of study drug administration (applicable only to female participants);
23. Women of childbearing potential who engaged in unprotected sex with partners within 14 days prior to screening;
24. Use of long-acting estrogen or progestin injections or implants within 6 months prior to screening, or such injections/implants still within efficacy period at the time of study drug administration (applicable only to female participants);
25. Other reasons deemed by the investigator as making the participant unsuitable for this study.