|- candidate number||15044|
|- NTR Number||NTR4047|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||26-jun-2013|
|- Secondary IDs||2013-002744-89 |
|- Public Title||Bioavailability of oral ciprofloxacin tablets versus suspension in pediatric cancer patients|
|- Scientific Title||Bioavailability of oral ciprofloxacin tablets versus suspension in pediatric cancer patients|
|- hypothesis||Whether the bioavailability of ciprofloxacin oral suspension and tablets are equivalent and can therefore be used interchangeably. |
|- Healt Condition(s) or Problem(s) studied||Cancer, Antimicrobial prophylaxis, Ciprofloxacin, Bioequivalence|
|- Inclusion criteria||- Age ≥1 years and < 19 years;|
- Patients treated with chemotherapy for pediatric cancer
- Patients who will receive ciprofloxacin treatment as antimicrobial prophylaxis according to standard supportive care guidelines
- Creatinine within normal limits according to age
- Possible to withhold antacids, sucralfate, iron, or other di/trivalent cations (e.g. zinc) for 6 h prior and 2 h after administration of ciprofloxacin on days of sampling (only one administration per day)
- Possible to withhold enteral feeding 4 h prior and 2 h after administration of ciprofloxacin on days of sampling (only one administration per day).
|- Exclusion criteria||- Patients unable/unwilling to take one of the ciprofloxacin formulations|
- Patients with cystic fibrosis
- Patients with celiac disease
- Patients with abnormalities in the gastrointestinal tract, including severe chemotherapy induced mucositis/diarrhea
- Known or suspected malabsorption state
- Previous allergic reactions to fluorchinolones
- Hepatic insufficiency.
|- mec approval received||no|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-aug-2013|
|- planned closingdate||1-aug-2015|
|- Target number of participants||15|
|- Interventions||Patients are treated with ciprofloxacin as standard treatment. However for this study, ciprofloxacin will be relabeled as study medication for the duration of the study. The total treatment study period is 14 days; subjects will start with 7 days of oral solution and thereafter switched to 7 days of tablets or vice versa. Patients will be randomized to determine the starting formulation. During the treatment with each formulation 6 blood samples will be taken at least 48 hours after start of treatment (samples at steady state). In total 18 samples will be taken (6 per formulation). |
|- Primary outcome||The parameters to determine the bioequivalence are Area Under the Curve (AUC), maximum concentration (Cmax), time of maximum concentration (Tmax) and bioavailability (F). 6 blood samples (>= 0,5 ml each) for the different formulations will be drawn from the available central line; one trough level and five additional samples after administration of ciprofloxacin. These will used to calculate the pharmacokinetic parameters utilizing NONMEM (non-linear mixed effects modeling). These parameters of the formulations of ciprofloxacin will be compared to each other within the same patient. All samples and therefore pk parameters will be determined during steady state.|
|- Secondary outcome||None|
|- Timepoints||Three sampling days (one for each formulation).|
Sampling day: trough level, ciprofloxacin intake, 0,5h, 1h, 1,5h, 2h, and 6h.
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES|| S.D.T. Sassen|
|- CONTACT for SCIENTIFIC QUERIES|| C.M. Zwaan|
|- Sponsor/Initiator ||Erasmus Medical Center, Rotterdam|
(Source(s) of Monetary or Material Support)
|Kinderen Kankervrij (KiKa)|
|- Brief summary||Rationale: Ciprofloxacin is an antibiotic drug which is routinely used as anti-microbial prophylaxis during the treatment of pediatric cancer patients. Both tablets and oral suspension are used interchangeably without altering the dose. However bioavailability and therefore exposure might differ between these formulations.
Objective: To determine the relative bioavailability of ciprofloxacin oral suspension versus oral tablets in pediatric cancer patients, and to determine the absolute bioavailability of tablets and suspension utilizing the 100% bioavailability of intravenous administration. This will enable correct dose adjustments when switching between the different formulations.
Study design: This is an open label randomized cross-over pharmacokinetic study in children using ciprofloxacin according to standard treatment guidelines.
Study population: 15 pediatric cancer patients in the range of 1-19 years, who are treated with ciprofloxacin prophylaxis as part of standard treatment.
Intervention: Patients receiving ciprofloxacin for antibiotic prophylaxis during chemotherapy treatment according to standard supportive care guidelines will be randomized to receive either ciprofloxacin tablets or oral suspension (50 mg/ml) for 7 consecutive days, and subsequently switch to the other formulation for the following 7 days, without a washout period in between. One random oral dose will be replaced by an intravenous dose of ciprofloxacin to determine the absolute bioavailability. During this period, blood samples will be drawn from the available Portacath catheter.
Main study parameters/endpoints: Determination of bioavailability (F), and related parameters: Tmax,ss, Cmax,ss, AUC.
|- Main changes (audit trail)|
|- RECORD||26-jun-2013 - 10-jul-2013|