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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01049022
First received: January 13, 2010
Last updated: July 21, 2015
Last verified: July 2015
  Purpose

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


Condition Intervention Phase
Infections
Drug: Moxifloxacin (Avelox, BAY12-8039)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Safety, Tolerability and Pharmacokinetics of Single Dose Intravenous Moxifloxacin in Pediatric Patients

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Area under the Concentration-Time Curve (AUC) of Moxifloxacin and its Metabolites [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Maximum Observed Drug Concentration in Plasma (Cmax) of Moxifloxacin and its Metabolites [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With Treatment Emergent Findings on Joint Assessment: Baseline [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
    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.

  • Number of Subjects With Treatment Emergent Findings on Joint Assessment : At any Time During Treatment [ Time Frame: Day 1 up to Year 5 (follow-up) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Time to Reach Maximum Drug Concentration in Plasma (tmax) of Moxifloxacin and its Metabolites [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Half Life Associated With Terminal Slope (t1/2) of Moxifloxacin and its Metabolites [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Total Amount Excreted in the Urine (Aeur) of Moxifloxacin and its Metabolites [ Time Frame: Baseline up to 36 hour post-infusion ] [ Designated as safety issue: No ]
    Aeur refers to the total amount of moxifloxacin excreted in urine.

  • Volume of Distribution at Steady State (Vss) of Moxifloxacin and its Metabolites [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Plasma Clearance (CL) of Moxifloxacin and its Metabolites [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Total body clearance of drug in plasma is expressed in litres per hour.

  • 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 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Maximum Observed Plasma Concentration Divided by Dose Per kilogram Body Weight (Cmax,Norm) of Moxifloxacin and its Metabolites [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 31
Study Start Date: May 2010
Study Completion Date: August 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Moxifloxacin (Avelox, BAY12-8039), Cohort 1 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.
Experimental: Moxifloxacin (Avelox, BAY12-8039), Cohort 2 Drug: 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.
Experimental: Moxifloxacin (Avelox, BAY12-8039), Cohort 3 Drug: 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.

  Eligibility

Ages Eligible for Study:   3 Months to 14 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01049022

Locations
United States, Arkansas
Little Rock, Arkansas, United States, 72202
United States, California
Orange, California, United States, 92868-3974
San Diego, California, United States, 92123-4282
United States, Kentucky
Louisville, Kentucky, United States, 40202
United States, Louisiana
New Orleans, Louisiana, United States, 70118-5799
United States, Massachusetts
Boston, Massachusetts, United States, 02115
United States, Missouri
Kansas City, Missouri, United States, 64108-9898
United States, Ohio
Cincinnati, Ohio, United States, 45229-3039
Cleveland, Ohio, United States, 44106
Toledo, Ohio, United States, 43606
United States, Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01049022     History of Changes
Other Study ID Numbers: 11826, 2012-000737-40
Study First Received: January 13, 2010
Last Updated: July 21, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Pharmacokinetics

Additional relevant MeSH terms:
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Combined
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on September 03, 2015