Charcot-Marie-Tooth
Conditions
Interventions
Single Ascending Dose (SAD) A1 Experiment Group:RTX-117 10mg
Single Ascending Dose (SAD) A1 Control Group:Placebo 10 mg
Single Ascending Dose (SAD) A2 Experiment Group:RTX-117 30 mg
Single Ascending Dose (SAD) A2 Control Group:Placebo 30 mg
Single Ascending Dose (SAD)&Food Effect (FE) A3 Experiment Group:RTX-117 60 mg
Single Ascending Dose (SAD)&Food Effect (FE) A3 Control Group:Placebo 60 mg
Single Ascending Dose (SAD) A4 Experiment Group:RTX-117 120 mg
Single Ascending Dose (SAD) A4 Control Group:Placebo 120 mg
Single Ascending Dose (SAD) A5 Experiment Group:RTX-117 200 mg
Single Ascending Dose (SAD) A5 Control Group:Placebo 200mg
Multiple Ascending Dose (MAD) B1 Experiment Group:RTX-117 30mg
Multiple Ascending Dose (MAD) B1 Control Group:Placebo 30mg
Multiple Ascending Dose (MAD) B2 Experiment Group:RTX-117 60mg
Multiple Ascending Dose (MAD) B2 Control Group:Placebo 60mg
Multiple Ascending Dose (MAD) B3 Experiment Group:RTX-117 120mg
Multiple Ascending Dose (MAD) B3 Control Group:Placebo 120mg
Sponsors
Shanghai Xuhui Central Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Male and female subjects aged 18-55 years (inclusive) at screening. 2. Subjects must sign the informed consent form before any study procedure, fully understand the study’s content, procedures, and possible adverse reactions, and be able to complete the study as required by the protocol. 3. In good general health (as assessed by the investigator based on medical history, surgical history, a complete physical examination, vital signs, laboratory tests, a 12-lead ECG, abdominal ultrasound and a chest radiograph), with no evidence of active or chronic disease. 4. Body Mass Index (BMI) = body weight (kg)/height2 (m2) between 18 and 28 kg/m² (inclusive). 5. Subjects (including their partners) agreed that they had no pregnancy plans from screening to 3 months after administration and voluntarily take effective contraceptive measures. Detailed contraception measures are provided in Section 8.1.
Exclusion criteria
Exclusion criteria: 1. Presence of clinically significant findings of any of the following conditions judged by the investigator (including but not limited to infection; disorders of the gastrointestinal, renal, hepatic, nervous, hematologic, endocrine, neoplastic, respiratory, immune, dermatologic, psychiatric, or cardiovascular/cerebrovascular systems) that would make implementation of the protocol or interpretation of the study results difficult., or that, in the investigator’s opinion, unacceptably increase the subject’s risk if he/she were to participate in the study. 2. Abnormal liver function: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) are >1.1 × upper limit of normal (ULN), or total bilirubin is >1.3×ULN, or creatine kinase (CK) >1.5×ULN. Repeat testing is permitted at the investigator’s discretion. 3. Estimated Glomerular Filtration Rate (eGFR) =450 msec (males) and =470 msec (females) (confirmed by repeated examinations); (2) A history of hypokalemia or family history of long QT syndrome; (3) Use of concomitant medicines that prolong QT/QTc (Refer to Appendix 2, Table 12). 6. Systolic BP =140 mmHg, confirmed by repeat; Diastolic BP >=90 mmHg, confirmed by repeat. 7. Use of prescription drugs, over-the-counter drugs, herbal medications, or vitamin,any health supplements within 14 days or 5 half-lives, whichever is longer, prior to dosing and antibiotics and systemic steroids within 30 days prior to dosing. Oral contraceptives are permitted). 8. Used or plan to use CYP3A4 inhibitors/inducers, P-gp/BCRP substrates, and CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A substrates within at least 7 days before the first dose and during this trial (Refer to Appendix 2, Table 13). 9. Those who smoked more than 5 cigarettes or equivalent tobacco products daily in the 3 months before screening, or drank = 14 units of alcohol per week (1 unit of alcohol ˜ 25 mL high liquor /84 mL wine /200 mL beer); Or disagree with the prohibition of smoking or alcohol during the trial; Or positive breath alcohol test during screening or baseline (Day-1). 10. Those who test positive for drugs in urine or have a history of drug abuse or use of drugs in the past 1 year. 11. Any vaccination within 14 days prior to Screening or anticipated vaccination while participating in the study. 12. Blood loss of non-physiological reasons or blood donation >200 ml within 3 months before screening, or plan to donate blood during this trial and within 30 days after the last dosing. 13. Receipt of an investigational product or device, or participation in a drug research study within a period of 90 days (or 5 half-lives of the drug, whichever is longer) before screening. 14. Serum virology tests at screening: positive for human immunodeficiency virus antibody (HIV-Ab); positive for hepatitis B surface antigen (HBsAg); positive for hepatitis B core antibody (HBcAb) with hepatitis B virus DNA (HBV-DNA) above the upper limit of the reference range; positive for hepatitis C antibody (HCV-Ab) (refer to Table 8). 15. Can not tolerate lumbar puncture (for the MAD study only), venous puncture blood colle
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse Event, AE;Severe Adverse Event, SAE;Vital Signs;Physical Examinations;Hematology;Biochemistry;Urinalysis;Coagulation;12-lead electrocardiograms (ECGs) data;Columbia-Suicide Severity Rating (C-SSRS);Maximum Administered Dose,MAD; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics Following single doses of RTX-117;Pharmacokinetics Following multiple doses of RTX-117;RTX-117 concentration in cerebral spinal fluid (CSF) and CSF-to-plasma concentration ratio; | — |
Countries
China
Contacts
Public ContactJingying Jia, Hongjie Qian
Shanghai Xuhui Central Hospital
Outcome results
None listed