Safety, Tolerability and Pharmacokinetics of Single Dose Intravenous Moxifloxacin in Pediatric Patients

Study Overview
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Brief Summary
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The purpose of this study is to describe the pharmacokinetics of moxifloxacin in children to see what the best dose should be for children in the future. Pharmacokinetics is to see how the body absorbs, distributes, breaks down and gets rid of the study drug. The pharmacokinetics of certain drugs may be altered in children due to developmental differences in various organ functions responsible for drug elimination, as well as in general distribution characteristics. The safety of moxifloxacin in children with infections will also be looked at. Results from this study will be used to guide dosing strategies of the larger clinical trial planned for children

Official Title
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Safety, Tolerability and Pharmacokinetics of Single Dose Intravenous Moxifloxacin in Pediatric Patients

Conditions
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Infections

Intervention / Treatment
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* Drug: Moxifloxacin (Avelox, BAY12-8039)
* Drug: Moxifloxacin (Avelox, BAY12-8039)
* Drug: Moxifloxacin (Avelox, BAY12-8039)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, ages 3 months through 14 years inclusive Receiving antibiotics for suspected or proven infection Exclusion Criteria: Body weight greater than 45 kg Patients taking anti-seizure medications within 30 days of moxifloxacin dosing Known or suspected allergy to quinolones History of tendon disease/disorder related to quinolone treatment Severe, life-threatening disease with a life expectancy of less than 48 hours and/or known rapidly fatal underlying disease (death expected within 2 months) Abnormal musculoskeletal evaluation at baseline assessment; or chronic musculoskeletal disease (eg, juvenile rheumatoid arthritis); or chronic illness with high risk for chronic or recurrent arthritis or tendinitis (eg, cystic fibrosis, chronic inflammatory bowel disease) Cardiac arrhythmia Evidence of renal or hepatic disease, based on laboratory findings (serum creatinine, total bilirubin, or ALT, > 1.5 times upper limit of normal) and physical exam Patients receiving Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents Patients taking any medication known to increase the QT interval, eg, amiodarone, astemizole, bepridil, chloroquine, chlorpromazine, cisapride, disopyuramide, dofetilide, droperidol, halofantrine, haloperidol, ibutilide, levomethadyl, mesoradazine, methadone, pimozide, procainamide, quinidine, sotalol, terfenadine Pregnancy Clinically relevant findings in the ECG Participation in another clinical study during the preceding 30 days1 (last treatment from previous study to first treatment of new study) Criteria which in the opinion of the investigator preclude participation for scientific reasons, for reasons of compliance, or for reasons of the patient's safety Patients taking another fluoroquinolone at the time of planned moxifloxacin dosing

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moxifloxacin (Avelox, BAY12-8039), Cohort 1<br> | Drug: Moxifloxacin (Avelox, BAY12-8039)<br>* Single intravenous (IV) infusion of moxifloxacin administered over 60 minutes, at an initial dosage of 5 milligram per kilogram per body weight (mg/kg/BW) with dose escalation to 6 mg/kg in subjects of age 6 years (yrs) to less than or equal to (<=) 14 years.<br>|
| Experimental: Moxifloxacin (Avelox, BAY12-8039), Cohort 2<br> | Drug: Moxifloxacin (Avelox, BAY12-8039)<br>* Single IV infusion of moxifloxacin administered over 60 minutes, at a dosage of 7 mg/kg/BW with dose escalation to 8 mg/kg in subjects of age 2 years to less than (<) 6 years; dose escalation was based on evaluations of the pharmacokinetic (PK) and safety data from the subjects in a preceding cohort.<br>|
| Experimental: Moxifloxacin (Avelox, BAY12-8039), Cohort 3<br> | Drug: Moxifloxacin (Avelox, BAY12-8039)<br>* Single IV infusion of moxifloxacin administered over 60 minutes, at a dosage of 9 mg/kg/BW with dose escalation to 10 mg/kg in subjects of age 3 months to < 2 years; dose escalation was based on evaluations of the PK and safety data from the subjects in a preceding cohort.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the Concentration-Time Curve (AUC) of Moxifloxacin and its Metabolites | The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. | Pre-dose, 1 hour (end of infusion), 1.5, 4, 8, 12 and 24 hours (Day 2) after start of infusion (samples at 36 h and 48 h were optional) | 
| Maximum Observed Drug Concentration in Plasma (Cmax) of Moxifloxacin and its Metabolites | Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. | Pre-dose, 1 hour (end of infusion), 1.5, 4, 8, 12 and 24 hours (Day 2) after start of infusion (samples at 36 h and 48 h were optional) | 
| Number of Subjects With Treatment Emergent Findings on Joint Assessment: Baseline | Joint assessment included formal physical examination of all joints with special care and attention to the weight-bearing joints (such as, knees, hips, and ankles) and to the shoulder girdle. All joints were examined for pain/tenderness, evidence of inflammation (i.e., redness, warmth, deformity, swelling or ballotable fluid), loss of function (to the extent this could be assessed in younger children and infants), and any restrictions to expected active/passive range of motion. An incidence count was reported as the number of subjects with at least one finding at baseline, regardless of side. | Baseline | 
| Number of Subjects With Treatment Emergent Findings on Joint Assessment : At any Time During Treatment | Joint assessment included formal physical examination of all joints with special care and attention to the weight-bearing joints (such as, knees, hips, and ankles) and to the shoulder girdle. An incidence count was reported as the number of subjects with at least one finding at any time during treatment, regardless of side. | Day 1 up to Year 5 (follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach Maximum Drug Concentration in Plasma (tmax) of Moxifloxacin and its Metabolites | tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. | Pre-dose, 1 hour (end of infusion), 1.5, 4, 8, 12 and 24 hours (Day 2) after start of infusion (samples at 36 h and 48 h were optional) | 
| Half Life Associated With Terminal Slope (t1/2) of Moxifloxacin and its Metabolites | Half life associated with terminal slope refers to the elimination of the drug. It is the time taken for the blood plasma concentration to reach half the concentration in the terminal phase of elimination. It is expressed in hours (h) and derived from the terminal slope of the concentration versus time curve. | Pre-dose, 1 hour (end of infusion), 1.5, 4, 8, 12 and 24 hours (Day 2) after start of infusion (samples at 36 h and 48 h were optional) | 
| Total Amount Excreted in the Urine (Aeur) of Moxifloxacin and its Metabolites | Aeur refers to the total amount of moxifloxacin excreted in urine. | Baseline up to 36 hour post-infusion | 
| Volume of Distribution at Steady State (Vss) of Moxifloxacin and its Metabolites | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steady-state. | Pre-dose, 1 hour (end of infusion), 1.5, 4, 8, 12 and 24 hours (Day 2) after start of infusion (samples at 36 h and 48 h were optional) | 
| Plasma Clearance (CL) of Moxifloxacin and its Metabolites | Total body clearance of drug in plasma is expressed in litres per hour. | Pre-dose, 1 hour (end of infusion), 1.5, 4, 8, 12 and 24 hours (Day 2) after start of infusion (samples at 36 h and 48 h were optional) | 
| Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose Per kilogram Body Weight (AUCnorm) of Moxifloxacin and its Metabolites | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AUCnorm is defined as AUC divided by dose per kg body weight. | Pre-dose, 1 hour (end of infusion), 1.5, 4, 8, 12 and 24 hours (Day 2) after start of infusion (samples at 36 h and 48 h were optional) | 
| Maximum Observed Plasma Concentration Divided by Dose Per kilogram Body Weight (Cmax,Norm) of Moxifloxacin and its Metabolites | Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. Cmax,norm is defined as Cmax divided by dose (mg) per kg body weight. | Pre-dose, 1 hour (end of infusion), 1.5, 4, 8, 12 and 24 hours (Day 2) after start of infusion (samples at 36 h and 48 h were optional) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics