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

Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01049022
• Other study ID #: 11826
• Secondary ID: 2012-000737-40
• Status: Completed
• Phase: Phase 1
• First received: January 13, 2010
• Last updated: July 21, 2015
• Start date: May 2010
• Est. completion date: August 2013

Study information

• Verified date: July 2015
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: August 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Months to 14 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Infections

Intervention

Drug:
• Moxifloxacin (Avelox, BAY12-8039)
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.
• Moxifloxacin (Avelox, BAY12-8039)
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.
• Moxifloxacin (Avelox, BAY12-8039)
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Primary	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	Yes
Primary	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)	Yes
Secondary	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)	No
Secondary	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)	No
Secondary	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	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No

External Links

•   Click here and search for drug information provided by the FDA.
•   Click here and search for information of websynopsis results
•   Click here and search for information on any recalls, market or product safety alerts by the FDA which might have occurred with this product.
•   Click here to find information about studies related to Bayer Healthcare products conducted in Europe