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 Study Sponsor: Study Number: 1114 Study Phase: Official Study Title: Test Product Clinical Trial Results Synopsis Bayer Healthcare AG III Study Design Description NCT A comparision of Iopromide and Iopamidol in computer tomography (CT) scanning of pediatric patients Therapeutic Area: Diagnostic Imaging Name of Test Product: Name of Active Ingredient: Dose and Mode of Administration: Reference Therapy/Placebo Ultravist (Iopromide, BAY ) Iopromide 300 The standard dosage was 2 ml/kg in subjects up to 10 kg weight, with a fixed dose of 20 ml in subjects from 10 to 20 kg and 40 ml in subjects from 20 to 40 kg. All other subjects were to receive 50 ml injection. Reference Therapy: Iopamidol 300 (Niopam) Dose and Mode of Administration: The standard dosage was 2 ml/kg in subjects up to 10 kg weight, with a fixed dose of 20 ml in subjects from 10 to 20 kg and 40 ml in subjects from 20 to 40 kg. All other subjects were to receive 50 ml injection. Duration of Treatment: Single investigational procedure Studied period: Date of first subjects first visit: 08 May 1989 Date of last subjects last visit: 10 Oct 1990 Study Center: One investigational site treated 122 subjects in the United Kingdom Methodology: The study was a randomized (2:1 in favor of Iopromide), single blind and group comparative study. The subjects were weighed to ensure an accurate body weight and a related dosage of the investigational preparation was given. Subject's details, including the reason for the investigation were recorded together with full details of any known concurrent medication. The indication for the CT (computed tomography) examination was documented prior to the procedure. Younger children and any particularly anxious children were sedated with quinal barbitone, 5 to 10 mg/kg (maximum 200 mg), or Diazemuls 0.1 to 0.2 mg/kg during the examination, and an anesthetic cream (EMLA cream) was used at the puncture site in all other cases. The contrast to be used was determined from the randomization list and injected by hand. Pulse and blood pressures were recorded prior to, during and immediately following the injection of contrast. Subjects were observed carefully during the injection of the contrast medium and the incidence of flushing, urticaria or if the Page 1 of 4

3 Indication/ Main Inclusion Criteria: Study Objectives: Evaluation Criteria: Statistical Methods: Number of Subjects: child starting to cry or scream, which in the radiologist's opinion was definitely related to the contrast medium, were recorded. This was not possible in sedated children. In all cases, any reactions occurring in the 24 hours following the procedure were recorded wherever possible. The images produced during the examination were rated as to the diagnostic quality (diagnostic, not diagnostic) and to the quality of the enhancement shown (excellent, good, fair, poor). Children aged 6 months to 16 years who required routine, contrast-enhanced CT scans of the head or body. Primary: The primary objective of the study was to compare the diagnostic quality of the images produced using Iopromide and Iopamidol. Secondary: The secondary objective was to compare the side-effects associated with the use of the 2 non-ionic iodinated contrast media in children undergoing CT examination. Efficacy (Primary): Quality of the images (graded on a 4-point scale). Efficacy (Secondary): Not applicable Safety: - Absolute changes from baseline (pre-injection) for pulse, systolic and diastolic blood pressure data. - Adverse events (AEs) that were directly related to the contrast medium. Efficacy (Primary): Ordered categorical data (CT diagnosis) was analyzed using the Mantel-Haenszel chi-squared test and all other categorical data using the likelihood ratio chi-squared test to indicate statistically significant differences between the two treatment groups. Efficacy (Secondary): Not applicable Safety: Absolute changes from baseline (pre-injection) were calculated for pulse, systolic and diastolic blood pressure data. These data were then analyzed using split-plot over time ANOVA (F-test). Any differences found were subsequently investigated using Duncan's multiple range test. The target recruitment was 150 subjects, but the study was terminated after 122 subjects due to slow recruitment and the length of time the study had run. Results Summary Subject Disposition and Baseline Study Results One hundred and twenty two subjects were enrolled, of which 40 subjects (22 males Page 2 of 4

4 and 18 females) belonged to the Iopamidol group and 82 subjects (41 males and 41 females) belonged to the Iopromide group. The mean age in the Iopamidol group was 9.74 years and the mean age in the Iopromide group was 9.54 years. There were no protocol violations and no subjects were withdrawn from the study. The study was terminated early due to the recruitment slowing and the length of time the study had run. There were no statistically significant differences between the Iopromide and Iopamidol groups for any of the demographic parameters except the area of the body to be examined and previous CT examination. There was a statistically significant difference between the 2 groups as to whether the subject had undergone a previous CT examination (p = 0.04); 23% (9 subjects) had a previous CT examination in the Iopamidol group, and 9% (7 subjects) in the Iopromide group. Iopromide was used to examine the body in 4% of cases (3 subjects) and the head and body in none, whereas Iopamidol was used to examine the head and body in 5% of cases (2 subjects) and the body alone in none. This resulted in a statistically signficant difference between the two groups (p = 0.03), but it was unlikely that this was clinically relevant as in the majority of cases only the head was examined (96% Iopromide, 95% Iopamidol). In the 16 cases where the subject had CT previously, 12 cases had received Iopamidol for that examination, 2 cases had no contrast medium and in one case the investigator did not known if the subject had been given contrast medium or not. Six subjects had a history of allergy to one of the following; hay fever, penicillin, house dust (rhinorrhea), and certain colored dyes. One subject had a history of asthma, although 4 subjects were receiving anti-asthma therapy. A total of 38 subjects were receiving concomitant medication divided here into 8 categories: antiepileptics (28 subjects), anti-asthma (4 subjects), and anti-epileptics/hypnotics, betablocker, thyroxin/asthma, anti-histamine, chemotherapy, or anti-hypertensive (1 subject each). Results Summary Efficacy The images produced during the examination were rated as to the quality of enhancement according to a 4 point scale (poor, fair, good, excellent) and to the diagnostic quality (diagnostic, not diagnostic). All the images were rated as either good or excellent in both contrast groups. There were no statistically significant differences in the quality of enhancement between Iopromide and Iopamidol. All the images were considered to have been diagnostic in the Iopromide and Iopamidol groups. The quality of CT scan was excellent in 51% of subjects in Iopromide group and in 40% subjects in Iopamide group. There were no statistical differences between the 2 groups with the majority of subjects having a normal CT scan (90% [74 subjects] in the Iopromide group and 73% [29 subjects] in the Iopamidol group). Table 1: Quality of computed tomography scans Iopromide Iopamidol Test N = 82 N = 40 n % n % Mantel-Haenzelchi-squared Excellent 42 51% 16 40% Good 40 49% 24 60% Fair 0 0 Poor 0 0 Probability test statistics Page 3 of 4

5 Results Summary Safety The incidence of individual side effects was low and similar for both groups. Two percent of subjects reported side effects spontaneously in the iopromide and 3% in the iopamidol groups, with 1% in the iopromide group having a side effect observed by the radiologist. Three subjects in the Iopromide group experienced mild taste in the mouth, severe taste in the mouth and moderate sneezing lasting 15 minutes. One subject of Iopamidol group experienced mild nausea. Three subjects (2 in Iopromide group and 1 in Iopamidol group) had no indication as to whether a spontaneously reported side effect or an observed side effect occurred. There was no statistically significant treatment effect and therefore no difference in pulse and systolic blood pressure measurements between the Iopromide and Iopamidol groups. There was no statistically significant treatment effect, but there was a statistically significant time effect (p = ) for diastolic blood pressure, with the during, and the post-injection measurements different from each other. In addition, a statistically significant difference between pre- and post-injection was also detected. These statistically signficant changes were not likely to be clinically relevant as they represented a maximum change of only 5 mm Hg which was very close to the accuracy of the blood pressure monitor (±3.5 mm Hg). Conclusions In this study, no difference was demonstrated between Iopromide and Iopamidol both in terms of diagnostic quality or the incidence of side effects. Iopromide and iopamidol were both well tolerated with only 4 patients having reported or observed adverse effects. Date Created or Date Last Updated: 23 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 ULTRAVIST injection Ultravist, Claritrast, Clarograf, Proscope, Ultragraf, Ultrakon Iopromide BAY Other Company Code(s) ZK Chemical Description Other Product Aliases N,N'-Bis(2,3-dihydroxypropyl)-2,4,6-triiodo-5- methoxyacetylamino-n-methylisophthalamide Date of last Update/Change: 5 July 2011 Date disclosed via Websynopsis