A Study Evaluating the Effect of a Single-dose Oral Administration of Nemonoxacin Capsule on QTc Intervals and Heart Rhythms of Healthy Subjects and the Influence of Food Intake on QTc Intervals and Pharmacokinetic Characteristics

NCT03362853 | Completed Phase 1

• 1 other identifier: TG-873870-C-7
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (10)

• ECG analysis - baseline-adjusted mean QTcB

  2 days

• ECG analysis - baseline-adjusted mean QTcP

  2 days

• Safety analysis

  33 days

• Maximum Plasma Concentration (Cmax)

  2 day

• Time at Which Maximum Plasma Concentration was Observed (Tmax)

  2 day

Study Arms (4)

Nemonoxacin 500Mg Capsule

EXPERIMENTAL

Drug: Nemonoxacin 500Mg Capsule; Drug: Moxifloxacin 400Mg Tablet; Drug: Nemonoxacin 750Mg Capsule; Drug: Placebo oral capsule

Nemonoxacin 750Mg Capsule

EXPERIMENTAL

Drug: Nemonoxacin 500Mg Capsule; Drug: Moxifloxacin 400Mg Tablet; Drug: Nemonoxacin 750Mg Capsule; Drug: Placebo oral capsule

Placebo oral capsule

PLACEBO COMPARATOR

Drug: Nemonoxacin 500Mg Capsule; Drug: Moxifloxacin 400Mg Tablet; Drug: Nemonoxacin 750Mg Capsule; Drug: Placebo oral capsule

Moxifloxacin 400Mg Tablet

ACTIVE COMPARATOR

Drug: Nemonoxacin 500Mg Capsule; Drug: Moxifloxacin 400Mg Tablet; Drug: Nemonoxacin 750Mg Capsule; Drug: Placebo oral capsule

Interventions

Nemonoxacin 500Mg Capsule DRUG

Receive a single dose in a fasting state

Also known as: TG-873870 500Mg

Moxifloxacin 400Mg Tablet; Nemonoxacin 500Mg Capsule; Nemonoxacin 750Mg Capsule; Placebo oral capsule

Moxifloxacin 400Mg Tablet DRUG

Receive a single dose in a fasting state

Moxifloxacin 400Mg Tablet; Nemonoxacin 500Mg Capsule; Nemonoxacin 750Mg Capsule; Placebo oral capsule

Nemonoxacin 750Mg Capsule DRUG

Receive a single dose in a fasting state

Also known as: TG-873870 750Mg

Moxifloxacin 400Mg Tablet; Nemonoxacin 500Mg Capsule; Nemonoxacin 750Mg Capsule; Placebo oral capsule

Placebo oral capsule DRUG

Receive a single dose in a fasting state

Moxifloxacin 400Mg Tablet; Nemonoxacin 500Mg Capsule; Nemonoxacin 750Mg Capsule; Placebo oral capsule

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• was post-menopausal for at least 1 year, or
• had been surgically sterilized, or
• met the following conditions if she was fertile: (i)her urine pregnancy test results were negative before she started the trial, and (ii)she agreed to use an approved birth control method (e.g. oral contraceptive, spermicide, condom, or intrauterine contraceptive device) throughout the study, and agreed to continue using birth control method within 1 month after the study, and (iii)she may not breastfeed.
• 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.

You may not qualify if:

• had any personal or family history of sudden cardiac death, myocardial ischemia, myocardial infarction, congestive heart failure, long QT syndrome, hypokalemia, myocarditis, exertional dyspnea, cerebrovascular accident, venous thromboembolism, etc; or
• needed to use medicine to treat QTc interval prolongation (e.g. Category I or III antiarrhythmic drugs, please refer to Appendix 1) or medicine to treat heart disease; or
• was found to have abnormal mean values of parameters in 12-lead ECG during the screening: PR \>240 ms, QRS \>110 ms, male QTcF \>430 ms (the automated machine-derived QTcF results in Lead II ECG were used and needed to be confirmed by the investigators), female QTcF \>450 ms (the automated machine-derived QTcF results in Lead II ECG were used and needed to be confirmed by the investigators), bradycardia (heart rate \<50 bpm); or
• had clinical abnormalities in 12-lead ECG during screening (e.g. atrioventricular block, torsades de pointes (TdP), other types of ventricular tachycardia, ventricular fibrillation and ventricular flutter, clinically significant T wave changes, or any 12-lead ECG abnormalities that may influence QTc intervals); or
• had systolic blood pressure \>140 mmHg or \<90 mmHg, diastolic blood pressure \>90 mmHg, pulse \<50 bpm or \>100 bpm during the screening; or
• had a positive result in hepatitis B virus or hepatitis C virus serology test; or
• had a positive pregnancy test result or was currently in lactation period; or
• was found to have any laboratory test value that was outside the reference value (normal value±10%) during the screening, and that was deemed to have clinical significance by investigators; or
• had a history of diabetes or cardiovascular disease, liver disease or kidney disease; or
• had malabsorption syndrome or any other gastrointestinal disease that may influence drug absorption; or
• had any history of epileptic seizures, or mental disease that may affect protocol compliance, or had a suicidal risk, or had history of alcohol or prohibited drug abuse; or
• had any disease known to severely affect the immune system, e.g. history of human immunodeficiency virus (HIV) infection, hematologic or solid organ malignancy, or had a splenectomy, etc; or
• had a hypersensitive idiosyncrasy or hypersensitivity to any drugs, including quinolones or fluoroquinolones; or
• had a surgery or trauma history within 6 months before receiving the study drug; or
• had, as shown from his/her medical history, used any known liver enzyme inducer or liver enzyme inhibitor such as benzedrine, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, phencyclidine, etc within 30 days before receiving the study drug; or

Sponsors & Collaborators

• TaiGen Biotechnology Co., Ltd.: lead

Related Publications (1)

• 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.

  PMID: 29803534 DERIVED

MeSH Terms

Interventions

nemonoxacin; Moxifloxacin; Tablets

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2017
• First Posted: December 5, 2017
• Study Start: June 25, 2012
• Primary Completion: August 10, 2012
• Study Completion: August 10, 2012
• Last Updated: December 6, 2017

Record last verified: 2017-12