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 Test Product Study Sponsor: Study Number: 1310 Study Phase: Official Study Title: Clinical Trial Results Synopsis Study Design Description Bayer Healthcare Pharmaceuticals Inc. III Therapeutic Area: Anti-Infectives Name of Test Product: Name of Active Ingredient: Dose and Mode of Administration: Reference Therapy/Placebo NCT Multi-Center, Prospective, Randomized, Third Party Blind Comparison of Oral Ciprofloxacin versus Continued Parenteral Ceftazidime in Neutropenic Pediatric Cancer Patients who have Responded to Initial Parenteral Therapy Ciprofloxacin (BAYO9867) Ciprofloxacin Reference Therapy: Ceftazidime Dose and Mode of Administration: Duration of Treatment: Up to 14 days. Maintenance phase: Ciprofloxacin 15 mg/kg (not to exceed 750 mg) orally every 12 hours and an infusion of saline placebo every 8 hours. Ciprofloxacin was provided as 50 mg, 100 mg and 250 mg capsules. Initial parenteral therapy: 3-7 days of ceftazidime 90 mg/kg/day. Maintenance phase: Ceftazidime 30 mg/kg (not to exceed 2 g) intravenously every 8 hours and placebo capsule(s) orally every 12 hours. Initial parenteral therapy: 3-7 days of ceftazidime 90 mg/kg/day. Studied period: Date of first subjects first visit: 20 Jun 1990 Date of last subjects last visit: 20 Aug 1991 Study Center(s): Eight investigational sites in the USA treated 14 subjects: 8 centers in USA. Methodology: This was a multi-center, prospective, randomized, third party blind study designed for 192 analyzable subjects. Neutropenic oncology subjects presenting with fever were treated initially with ceftazidime. Subjects with no infection documented and who had defervesced after 3-7 days of ceftazidime, were randomized to continue parenteral therapy with ceftazidime or were switched to oral ciprofloxacin. Prior to randomization, subjects were stratified into 2 groups based on their type of underlying malignancy. Treatment was continued until their absolute neutrophil count was >500/mm 3 on two consecutive days or development of fever requiring treatment with another anti-bacterial regimen or they adverse events requiring discontinuation of study drug or completion of 14 days of total antimicrobial therapy (initial ceftazidime therapy plus post-randomization study drug). Clinical Page 1 of 4

3 Indication/ Main Inclusion Criteria: Study Objectives: Evaluation Criteria: Statistical Methods: responses defined as success, success with modification or failure were recorded. Hospitalized pediatric neutropenic oncology subjects between 5 to 18 years of age with no documented infection and clinical response to initial parenteral therapy with ceftazidime on 3 rd, 4 th, 5 th,6 th or 7 th day of therapy were included in the study. Overall: The objective of this study was to compare the safety and efficacy of oral ciprofloxacin (30 mg/kg/day), with that of continued parenteral therapy with ceftazidime (90 mg/kg/day), in neutropenic pediatric oncology subjects who have responded to initial parenteral therapy with ceftazidime. Efficacy (Primary): Comparison of the incidence of treatment failure in each study arm. Efficacy (Secondary): Comparison of the duration of (intervention-free) double-blind therapy between the two treatment groups, duration of neutropenia, survival through period of neutropenia. Safety: Incidence, severity, relationship to treatment, outcome and duration of adverse events was tabulated and laboratory tests and joint evaluations were performed. Pharmacokinetics: Peak and trough serum samples were obtained following the first and sixth doses of oral study medication to document the absorption and elimination of ciprofloxacin. Drug assays, the times drawn, hours postdose and time at end of dose were recorded. Efficacy (Primary): It was planned to assess equivalence of the treatment failure rates with adjustment for center by stratum effects employing a Mantel- Haenszel procedure. Statistical significance (p-value) were to be reported for testing the null hypothesis that the ciprofloxacin failure rate exceeds that of ceftazidime by more than 20%. Due to a small sample size, this comparison of efficacy was not possible. Safety: Incidence rates for adverse events were compared across the two groups using the Fisher Exact Test or chi-square tests. Changes in laboratory measurements and bone and joint exams were investigated. Number of Subjects: It was planned to enroll one hundred ninety two valid subjects, however study was terminated after 14 months during which only 14 subjects were randomized. Five subjects were randomized to receive ciprofloxacin and 9 were randomized to continue receiving ceftazidime. Page 2 of 4

4 Results Summary Subject Disposition and Baseline Study Results Fourteen subjects were enrolled in this study of which 5 received ciprofloxacin and 9 continued to receive ceftazidime. There were 13 subjects valid for efficacy and safety analysis. One subject in the ciprofloxacin group was discontinued prematurely (Day 1) and invalid for analysis of efficacy due to an absolute neutrophil count (ANC) >500/mm 3. Of the 13 subjects evaluable for efficacy, 4 subjects were randomized to the ciprofloxacin group and 9 were randomized to the ceftazidime group. There were 3 males and one female in ciprofloxacin group. Mean weight in ciprofloxacin group was 29.5 pounds (range =18-40 pounds) and mean age was 7.8 years (range = 6-9 years). For ceftazidime group, there were 6 males and 3 females. Mean weight in this group was 37.3 pounds (range = pounds) and mean age was 9.6 years (range = 5-15 years). Seventy-five percent of the ciprofloxacin group were in good health and 25% were in fair health. In the ceftazidime group, 22.2% were in excellent health, 55.6% in good health and 22.2% were in fair health. The only other systemic antimicrobial agent that could be administered during the study period was trimethoprim/sulfamethoxazole (TMP/SMZ) for prophylaxis. One subject out of 4 in the ciprofloxacin group and 4 subjects out of 9 in the ceftazidime group received TMP/SMZ. Results Summary Efficacy For the clinical response of the subjects to the antibacterial therapies, all subjects in this study fell under the category of "Success" defined as: the subject remained afebrile on the study antibacterial regimen and recovered from the episode of neutropenia without any modification of the initial regimen. Four subjects in this study did not have a documented resolution of neutropenia during therapy but all had neutrophil counts >100 mm 3. In the ceftazidime group, one subject had a neutrophil count of 261/mm 3 on day 11 and one subject had a count of 384 mm 3, 75 days after therapy. In the ciprofloxacin treatment group, one subject had a count of 132/mm 3 on day 11 and one subject was discontinued on day 1 for an ANC of 306/mm 3. Following table shows that all subjects in both treatment groups remained afebrile during therapy, and 314 (75%) in the ciprofloxacin group and 719 (78%) in the ceftazidime group had resolved neutropenia. Table 1: Temperature and Neutrophil Count (Subjects Valid for Analysis of Efficacy) Ciprofloxacin (N=4) Ceftazidime (N=9) Number of subjects. N % N % AfebrileSubjects Resolved Neutropenia Table 2: Efficacy Analysis Population: Subjects Valid for Analysis of Efficacy Ciprofloxacin (N=4) Ceftazidime (N=9) N % N % Success A Success with modification B Failure C A Afebrile subjects recovered from episode of neutropenia without any modifications of the initial regimen. B Subject develops new fever after having defervesced that requires an antimicrobial agent. C The addition of any antibacterial agent because of persistent fever due to bacterial infection or death secondary to infection. Page 3 of 4

5 To ensure compliance, all missed doses were charted and reported. There was no problem in this study with the subject's ability to swallow capsules. Subjects receiving ciprofloxacin had a mean of 6.0 days duration of treatment (range 2-11 days). Subjects receiving ceftazidime had 6.2 days of treatment (range 3-11 days). Results Summary Safety One of 9 subjects in the ceftazidime group reported vomiting and epistaxis, both of which were considered to be intercurrent conditions/illnesses/injuries. These events were reported as mild to moderate in intensity, required no action and resolved. One of 9 subjects in the ceftazidime group reported diarrhea of mild intensity assessed as possibly related to the study drug. No action was required and the event resolved. No adverse events or intercurrent conditions/illnesses/injuries were reported in the ciprofloxacin group. There were no deaths reported in this study. No subjects discontinued therapy prematurely due to adverse reactions, nor were there any serious adverse events. Results Summary Pharmacokinetics Drug assays were drawn between Days 1 and Days 5 of the study. Only one subject had drug assays analyzed and the results were as follows: Table 3: Results on the Analysis of Drug Assays Drawn from a Single Subject. Day Hours Post-Dose Ciprofloxacin Conc. (µg/ml) Conclusion(s) In the 14 subjects studied, oral ciprofloxacin 15 mg/kg every 12 hours and ceftazidime 30 mg/kg IV every 8 hours were effective in neutropenic pediatric cancer subjects. All subjects remained afebrile during treatment. Ciprofloxacin showed no adverse effects on musculoskeletal exams during treatment. Ciprofloxacin was well tolerated with few adverse events reported. Oral ciprofloxacin provided an option to parenteral therapy in neutropenic cancer subjects. Date Created or Date Last Updated: 25 Aug 2011 Page 4 of 4