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A randomized, single-center, placebo and positive control, 4-period and 4-crossover clinical study with the following main purposes: (1) To evaluate the effect of a single-dose oral administration of nemonoxacin malate capsule on QTc intervals and heart rhythms of healthy subjects. (2) To evaluate the influence of food intake on QTc intervals and pharmacokinetic characteristics.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nemonoxacin 500Mg Capsule | Experimental |
| |
| Nemonoxacin 750Mg Capsule | Experimental |
| |
| Placebo oral capsule | Placebo Comparator |
| |
| Moxifloxacin 400Mg Tablet | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nemonoxacin 500Mg Capsule | Drug | Receive a single dose in a fasting state |
|
| Measure | Description | Time Frame |
|---|---|---|
| ECG analysis - baseline-adjusted mean QTcF | To compare the post-dosing placebo-corrected, baseline-adjusted mean QTcF differences (ΔΔQTcF) of nemonoxacin 500 mg/750 mg groups and placebo group at corresponding time points with the manually measured QTcF in Lead II of ECG. | 2 days |
| Measure | Description | Time Frame |
|---|---|---|
| ECG analysis - baseline-adjusted mean QTcB | To compare the post-dosing placebo-corrected, baseline-adjusted mean QTcB differences (ΔΔQTcF) of nemonoxacin 500 mg/750 mg groups and placebo group at corresponding time points with the manually measured QTcB in Lead II of ECG. | 2 days |
| ECG analysis - baseline-adjusted mean QTcP |
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Inclusion Criteria:
Male or female, aged between 18 and 40 during the screening period.
A volunteer's Body Mass Index (BMI) had to be between 19~24 kg/m2, and a male volunteer's body weight was no less than 50 kg, while female, no less than 45 kg.
A subject was judged as a healthy one by investigators according to his/her medical history, physical examination, 12-lead ECG examination, and laboratory test results.
A female subject:
A male subject had to use a reliable birth control method (using a condom, or his partner executed the foresaid criteria) throughout the study and within 1 month after the study.
A subject had never used tobacco or nicotine products within 1 month before receiving the study drug.
A subject had never drunk alcohol or drunk more than 12 times within 3 months before receiving the study drug.
A subject was willing to completely abstain from foods or beverages containing caffeine or xanthine such as coffee, tea, chocolate, alcohol, grapefruit juice, orange juice, etc within 24 hours before receiving the study drug and during his/her Stage I ward stay.
A subject was willing to sign the Informed Consent Form.
Exclusion Criteria:
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29803534 | Derived | Zhao C, Lv Y, Li X, Hou F, Ma X, Wei M, Kang Z, Cui L, Xia Y, Liu Y, Tian J. Effects of Nemonoxacin on Thorough ECG QT/QTc Interval: A Randomized, Placebo- and Positive-controlled Crossover Study in Healthy Chinese Adults. Clin Ther. 2018 Jun;40(6):983-992. doi: 10.1016/j.clinthera.2018.04.014. Epub 2018 May 24. |
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Stage I: the administration sequences of the 4 groups were CABD, ADCB, BCDA and DBAC respectively. D represents moxifloxacin, the positive control drug, for which an open design was adopted. For the other 3 groups, i.e. 500 mg nemonoxacin, 750 mg nemonoxacin, and placebo, a double-blind design was employed.
Stage II: An open design for 12 subjects who had completed Stage I to receive a single oral dose of 500 mg nemonoxacin after taking a high-fat test meal
|
| Moxifloxacin 400Mg Tablet | Drug | Receive a single dose in a fasting state |
|
| Nemonoxacin 750Mg Capsule | Drug | Receive a single dose in a fasting state |
|
|
| Placebo oral capsule | Drug | Receive a single dose in a fasting state |
|
To compare the post-dosing placebo-corrected, baseline-adjusted mean QTcP differences (ΔΔQTcF) of nemonoxacin 500 mg/750 mg groups and placebo group at corresponding time points with the manually measured QTcP in Lead II of ECG. |
| 2 days |
| Safety analysis | An analysis of adverse event (number and percentage of subjects) was conducted based on dosage groups | 33 days |
| Maximum Plasma Concentration (Cmax) | The analysis was conducted using the well-validated software (WinNolin and DAS programs). A non-compartment model was used to analyze the plasma concentration-time data of nemonoxacin and moxifloxacin, thus the pharmacokinetic parameter was evaluated, and a descriptive summary of the plasma concentration-time data by dosage groups and time points were presented. Also, a descriptive summary of pharmacokinetic parameters were made based on dosage groups. | 2 day |
| Time at Which Maximum Plasma Concentration was Observed (Tmax) | The analysis was conducted using the well-validated software (WinNolin and DAS programs). A non-compartment model was used to analyze the plasma concentration-time data of nemonoxacin and moxifloxacin, thus the pharmacokinetic parameter was evaluated, and a descriptive summary of the plasma concentration-time data by dosage groups and time points were presented. Also, a descriptive summary of pharmacokinetic parameters were made based on dosage groups. | 2 day |
| Area Under the Plasma Concentration-Time Curve Calculated to the Last Measured Concentration (AUC(0~t)) | The analysis was conducted using the well-validated software (WinNolin and DAS programs). A non-compartment model was used to analyze the plasma concentration-time data of nemonoxacin and moxifloxacin, thus the pharmacokinetic parameter was evaluated, and a descriptive summary of the plasma concentration-time data by dosage groups and time points were presented. Also, a descriptive summary of pharmacokinetic parameters were made based on dosage groups. | 2 day |
| Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC(0~∞)) | The analysis was conducted using the well-validated software (WinNolin and DAS programs). A non-compartment model was used to analyze the plasma concentration-time data of nemonoxacin and moxifloxacin, thus the pharmacokinetic parameter was evaluated, and a descriptive summary of the plasma concentration-time data by dosage groups and time points were presented. Also, a descriptive summary of pharmacokinetic parameters were made based on dosage groups. | 2 day |
| Lambda-z (λz) | The analysis was conducted using the well-validated software (WinNolin and DAS programs). A non-compartment model was used to analyze the plasma concentration-time data of nemonoxacin and moxifloxacin, thus the pharmacokinetic parameter was evaluated, and a descriptive summary of the plasma concentration-time data by dosage groups and time points were presented. Also, a descriptive summary of pharmacokinetic parameters were made based on dosage groups. | 2 day |
| half-life (t1/2) | The analysis was conducted using the well-validated software (WinNolin and DAS programs). A non-compartment model was used to analyze the plasma concentration-time data of nemonoxacin and moxifloxacin, thus the pharmacokinetic parameter was evaluated, and a descriptive summary of the plasma concentration-time data by dosage groups and time points were presented. Also, a descriptive summary of pharmacokinetic parameters were made based on dosage groups. | 2 day |
| Oral Clearance (CLt/F) | The analysis was conducted using the well-validated software (WinNolin and DAS programs). A non-compartment model was used to analyze the plasma concentration-time data of nemonoxacin and moxifloxacin, thus the pharmacokinetic parameter was evaluated, and a descriptive summary of the plasma concentration-time data by dosage groups and time points were presented. Also, a descriptive summary of pharmacokinetic parameters were made based on dosage groups. | 2 day |
| ID | Term |
|---|---|
| C543520 | nemonoxacin |
| D000077266 | Moxifloxacin |
| D013607 | Tablets |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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