Clinical Study Synopsis

Transcription

1 Clinical Study Synopsis This document is not intended to replace the advice of a healthcare professional and should not be considered as a recommendation. Patients should always seek medical advice before making any decisions on their treatment. Healthcare Professionals should always refer to the specific labeling information approved for the patient's country or region. Data in this document or on the related website should not be considered as prescribing advice. The study listed may include approved and non-approved formulations or treatment regimens. Data may differ from published or presented data and are a reflection of the limited information provided here. The results from a single trial need to be considered in the context of the totality of the available clinical research results for a drug. The results from a single study may not reflect the overall results for a drug. The following information is the property of Bayer HealthCare AG. Reproduction of all or part of this report is strictly prohibited without prior written permission from Bayer HealthCare AG. Commercial use of the information is only possible with the written permission of the proprietor and is subject to a license fee. Please note that the General Conditions of Use and the Privacy Statement of bayerhealthcare.com apply to the contents of this file.

2 Clinical Trial Results Synopsis Study Design Description Study Sponsor: Bayer Healthcare AG Study Number: 0575 Study Phase: Official Study Title: II Therapeutic Area: Anti-Infectives NCT A prospective, open, multi-centre study to determine the safety of IV and oral ciprofloxacin in the treatment of selected paediatric infections Test Product Name of Test Product: Name of Active Ingredient: Dose and Mode of Administration: Cipro (Ciprofloxacin, BAYQ3939) Ciprofloxacin Intravenous ciprofloxacin infusion (200 mg/100 ml): 5 mg/kg twice a day, 10 mg/kg twice a day or 10 mg/kg thrice a day, intravenously over 60 minutes. Ciprofloxacin suspension (5 g/100 ml): 7 mg/kg twice a day, 14 mg/kg twice a day, or 20 mg/kg twice a day, orally. Reference Therapy/Placebo Reference Therapy: Not applicable Dose and Mode of Administration: Not applicable Duration of Treatment: Minimum of 3 days and a maximum of 6 weeks at the investigator's discretion depending on the type and severity of infection. Studied period: Date of first subjects first visit: 20 Feb 1997 Date of last subjects last visit: 17 Aug 1999 Study Center(s): Five investigational sites treated 60 subjects in one country, South Africa. Methodology: This was a prospective, non-randomized, uncontrolled (single treatment arm), open, multi-centre study. A follow-up assessment was performed at days post-treatment and a long-term follow-up was to be performed at 6 months post-treatment in cases where pathological joint changes had occurred. Physical examinations were performed daily during treatment and laboratory tests at least once a week during treatment. Upon detection of any symptomatic joint, a detailed clinical examination, ultrasound examination and MRI scan was performed as soon as possible and repeated at 6 months. Blood samples (±1.5 ml each) from a subset of 40 subjects were to be collected for drug concentration measurements. The exact sampling times, times of drug intake as well as the exact times of the Page 1 of 4

3 Indication/ Main Inclusion Criteria: Study Objectives: Evaluation Criteria: Statistical Methods: precursor doses were to be recorded. The study was prematurely terminated due to the slow recruitment rate. Subjects between the ages of 3 months and 14 years with one of the following diagnoses were enrolled in the study: complicated urinary tract infection, osteomyelitis (acute or chronic) with documented Pseudomonas aeruginosa or other gram-negative organisms not readily treated with other oral agents, dysentery in immunocompromised or malnourished children or dysentery with confirmed multi-drug resistant organisms resistant to other non quinolone agents, otorrhoea due to complicated otitis media, bacteraemia and/or sepsis with a multi-resistant bacterium, pneumonia caused by confirmed or suspected gram-negative organisms. Primary: The primary objective of this study was to evaluate the safety of intravenous (IV) and oral ciprofloxacin in the treatment of selected paediatric infections in subjects younger than 14 years where ciprofloxacin offered a therapeutic benefit, i.e. in the presence of a multiresistant pathogen, life threatening infection, or in circumstances where there is no oral treatment. In addition, plasma samples were collected during the course of treatment from a subset of at least 40 subjects in order to determine descriptive population pharmacokinetics. Secondary: The secondary objective was the assessment of the efficacy of ciprofloxacin. Efficacy (Primary): Clinical response at the end of study treatment. Efficacy (Secondary): - The clinical assessment at the end of the entire study period, i.e., days after the end of the study drug treatment. - The bacteriological response at the end of study drug treatment. Safety: Adverse events, laboratory tests, serial examination of joints were done based on: clinical examination of joint function by the appearance of joints and range of motion, ultrasound examination of joints and nuclear magnetic resonance imaging examination of joints. Pharmacokinetics: Plasma samples were collected from a subset of at least 40 subjects during the course of treatment in order to determine descriptive population pharmacokinetics. Efficacy (Primary) The clinical responses were listed for all subjects and the cure rate was calculated. Efficacy (Secondary) The bacteriological responses were listed for all subjects and the cure rate was calculated. Page 2 of 4

4 Number of Subjects: Safety: The primary objective of the study was to assess the safety of ciprofloxacin. The statistical analysis was descriptive. Frequencies of adverse events were reported. Individual laboratory values were listed with summary statistics for each variable at each assessment time. The frequency of abnormal laboratory values was evaluated. Pharmacokinetics: A descriptive population pharmacokinetic analysis was performed. A total of 60 subjects were enrolled and were included in the safety analysis. Fifty nine subjects were valid for Intention-to-treat/per protocol (ITT/PP) analysis and 38 subjects were valid for intention-totreat/ per protocol microbiological evaluation (ITT/PP MBE) analysis. Fifty five subjects completed the study. Results Summary Subject Disposition and Baseline Study Results Overall 60 subjects were enrolled in the study of whom 55% were female and 45% were male. Most of the subjects were Black (76.7%). The mean age at enrolment was 2.2 years (male: 2.1 years, female: 2.3 years). Subjects were enrolled in the study for the following conditions: complicated urinary tract infection (15.3%), dysentery (28.8%), otorrhoea (11.9%), bacteraemia and/or sepsis (13.6%) and pneumonia (35.6%). Fifty-eight subjects (96.7%) valid for the safety analysis had at least one medical history finding or physical examination abnormality. The most frequently occurring findings were as follows: human immunodeficiency virus infection, unspecified (31.7%), other and unspecified noninfectious gastro-enteritis and colitis (20.0%), acute upper respiratory infections of unspecified site (18.3%), candidiasis of mouth (16.7%), pneumonia organism unspecified (15.0%) and diaper or napkin rash (11.7%). Results Summary Efficacy ITT/PP and ITT/PP MBE analyses were performed on the primary and secondary efficacy variables. The primary efficacy parameter was the clinical response at the end of study treatment. The clinical success rate was 79.7% for subjects valid for the ITT/PP analysis. Table 1: Clinical response: End of Treatment Population/Clinical assessment Treatment group Ciprofloxacin IV/oral n % ITT / PP population Clinical cure Clinical failure Indeterminate Total The secondary efficacy variables were clinical response days post-treatment and the bacteriological response at the end of study treatment. For the subjects valid for the ITT/PP analysis the success rate was 66.1 %. Page 3 of 4

5 Table 2: Clinical response: days Post-Treatment Population/Clinical assessment Treatment group Ciprofloxacin IV/oral n % ITT / PP population Missing Continued Clinical cure Clinical recurrence/relapse a Indeterminate Total a - Includes failures at End of Treatment Bacteriological success was evaluated as "eradication" and "presumed eradication". The bacteriological success rate was therefore 25/38 subjects or 65.8% of subjects valid for the IIT/PP MBE analysis. Results Summary Safety Table 3: Bacteriological response: End of Study Treatment Population/Bacteriological assessment Treatment group Ciprofloxacin IV/oral n % ITT / PP MBE population Missing Eradication Presumed eradication Persistence Superinfection Indeterminate Total Of the 60 subjects who were included in the safety analysis, 27 (45.0%) subjects had 54 treatment-emergent signs and symptoms (TESS) events. A drug-related TESS event was defined as any TESS event with a relationship to the study drug rated as "possible" or "probable". Four subjects (6.7%) had 6 drug-related TESS events namely, lack of drug effect, diarrhoea, abnormal liver function tests, oral moniliasis, thrombocythemia and arthrosis. One death occurred in the study. The subject died on Day 7 (relative to start of treatment [Day one]) due to lack of drug effect (treatment failure). Two subjects enrolled in the study died during follow-up due to underlying disease. Four subjects experienced the following serious adverse events: pneumothorax, convulsion, subdural haematoma and larynx oedema. The larynx oedema had improved at conclusion of the study, while the other adverse events had resolved. One subject was prematurely withdrawn from the study due to arthrosis, diarrhoea and pneumonia. The most frequently occurring TESS events were: diarrhoea (5.0%) oral moniliasis (5.0%) rash (5.0%) and pharyngitis (5.0%). Conclusion(s) As a result of the low incidence of drug-related adverse events, it can be concluded that ciprofloxacin was safe in the treatment of selected infections in the paediatric population evaluated during this study. At the end of treatment, a clinical success rate of 79.9% was observed, which can be considered high given the clinical profile of the subject population, namely subjects with complicated or resitant infections and multiple co-morbidities. Date Created or Date Last Updated: 25 Aug 2011 Page 4 of 4

6 Appendix to Clinical Study Synopsis Product Identification Information Product Type US Brand/Trade Name(s) Brand/Trade Name(s) ex-us Generic Name Main Product Company Code Drug Cipro IV [i.v. Formulation] Baycip Ciflox Ciprin Cipro Ciprofloxacin Ciprobay Ciproxan Ciproxin Ciproxine Ciproxina Ciprofloxacin BAYq3939 Other Company Code(s) Chemical Description Other Product Aliases Ciprofloxacin: 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1- piperazinyl)-3-quinolinecarboxylic acid Date of last Update/Change: 10 Nov 2010