Official Title: “An Open-Label Randomized Multiple-Dose Study to Evaluate Levofloxacin Steady-State Pharmacokinetics and Safety in Subjects With Varying Degrees of Renal Function”

The primary objective was to evaluate the pharmacokinetics and safety of two dosing regimens of levofloxacin in patients with varying degrees of renal function.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Pharmacokinetics Study

In this multiple-dose study conducted at 4 centers, the pharmacokinetics of two dosing regimens of levofloxacin were assessed in medically stable men and women with varying degree of renal function. The study consisted of a 21 day pretreatment screening phase, a 7-day open label treatment phase, and a 7 day posttreatment phase (or a follow-up phase for subjects with early study withdrawal). Patients were randomized into 1 of 10 treatment groups, for a total of 6 patients per group, based on degree of renal function to ensure that creatinine clearance values within each group represented the full range of values defined in the Food and Drug Administration's (FDA) 1998 guideline for pharmacokinetic studies in patients with impaired renal function. Fifty-nine patients were enrolled in the study. All patients received a single 750-mg dose of levofloxacin on Day 1; subsequent doses of either 250, 500, or 750 mg of levofloxacin (q24h or q48h) were based on renal function. Blood samples were collected from each patient from Day 1 to Day 14 for pharmacokinetic evaluation. Urine was collected on Days 1 and 7 before dosing and over specific time intervals up to 24 or 48 hours postdosing depending on the patient's dosing regimen. Dialysate samples were collected on Day 7 from HD patients immediately before dosing (as dialysis began) and at the end of the dialysis treatment. Patients were confined overnight at the study unit on Days 0, 1, 6, and 7, and remained confined until the 24 hour blood samples were collected on Days 2 and 8.

Safety was based on the incidence, relationship to therapy, and severity of treatment-emergent adverse events and on changes in clinical laboratory values (hematology, chemistry, and urinalysis), vital sign measurements, electrocardiograms (ECGs), and physical examination findings.

Single 750-mg dose of levofloxacin on Day 1; subsequent doses of Levofloxacin 250 milligram (mg), 500 mg, and 750 mg tablets administered every 24 hours for 7 days or every 48 hours for 7 days

Intervention(s) in this Clinical Trial

• Drug: Levofloxacin

Primary Measures

• Evaluation of the pharmacokinetics of two dosing regimens of levofloxacin in renally impaired and dialysis patients.

Secondary Measures

• Safety of two dosing regimens of levofloxacin in renally impaired and dialysis patients.

Inclusion Criteria:

• BMI between 18 and 35 kg/m2
• No prescription or over-the-counter medications for previous 7 days
• Negative tests for drug and alcohol abuse, HIV, hepatitis B and hepatitis C
• Medically stable based on medical history, physical examination, 12-lead electrocardiograms, toxicology, antigen, and antibody screens, and clinical laboratory evaluations
• Stable renal function based on calculated creatine clearance for non-dialysis patients and the same dialysis treatment for at least 6 months prior to screening for dialysis patients
• Patients with creatinine clearance ≤80 mL/min who require treatment for renal impairment or other chronic disease (e.g., well-controlled diabetes, hypertension) must be on a stable treatment plan (medicines, doses, and regimens) for at least 2 months prior to Day 1 and during the entire study
• Hematocrit (hct) within the normal range based on patients' renal function at screening

Exclusion Criteria:

• Allergic reaction to quinolones
• Known or suspected allergy to heparin
• Clinically significant ECG or clinical laboratory abnormalities
• Creatinine clearance <80 mL/min whose medical condition was unstable
• Creatinine clearance >= 80 mL/min who required concomitant medication during the study
• Poorly controlled type 1 or type 2 diabetes
• Patients with creatinine clearance >= 50 mL/min with screening blood pressure outside the normal range (sitting systolic blood pressure <90 or >140 mm mercury [Hg] or diastolic blood pressure <60 or >90 mm Hg)
• Patients with CLCR <50 mL/min who had sitting systolic blood pressure <90 or >160 mm
• Hg, or diastolic blood pressure <60 or >90 mm Hg
• Required warfarin treatment
• Required immunosuppressive medications for treatment of immune-mediated renal disease or kidney transplant
• Pregnant or breastfeeding

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Overall Clinical Trial Officials and Contacts

Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Clinical Trial Study Director Johnson & Johnson Pharmaceutical Research & Development, L.L.C.  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00645437

Study ID Number: CR004174

ClinicalTrials.gov Identifier: NCT00645437

Health Authority: United States: Food and Drug Administration

An Open-Label Randomized Multiple-Dose Study to Evaluate Levofloxacin Steady-State Pharmacokinetics and Safety in Subjects With Varying Degrees of Renal Function