abcd Clinical Study Synpsis fr Public Disclsure This clinical study synpsis is prvided in line with Behringer Ingelheim s Plicy n Transparency and Publicatin f Clinical Study Data. The synpsis which is part f the clinical study reprt had been prepared in accrdance with best practice and applicable legal and regulatry requirements at the time f study cmpletin. The synpsis may include apprved and nn apprved uses, dses, frmulatins, treatment regimens and/r age grups; it has nt necessarily been submitted t regulatry authrities. A synpsis is nt intended t prvide a cmprehensive analysis f all data currently available regarding a particular drug. Mre current infrmatin regarding a drug is available in the apprved labeling infrmatin which may vary frm cuntry t cuntry.. Additinal infrmatin n this study and the drug cncerned may be prvided upn request based n Behringer Ingelheim s Plicy n Transparency and Publicatin f Clinical Study Data. The synpsis is supplied fr infrmatinal purpses nly in the interests f scientific disclsure. It must nt be used fr any cmmercial purpses and must nt be distributed, published, mdified, reused, psted in any way, r used fr any ther purpse withut the express written permissin.
Behringer Ingelheim Page: 1 f 6 Internatinal GmbH This is the Internatinal GmbH 16 Dec 2002-15 May 2003 Title f study: Investigatr: A Phase IV Safety Trial in Pediatric Patients (Ages 2-5) with Rhinrrhea Assciated with a Cmmn Cld r Allergy Multi-center study withut fficial designatin f a Principal f Crdinating Investigatr (See Sectin 16.1.4 fr a cmplete list f investigatrs) Study center(s): 19 Publicatin (reference): Clinical phase: Objectives: Methdlgy: IIIb/IV T determine the safety f Nasal Spray 0.06% in pediatric patients (ages 2-5 years) with symptms f rhinrrhea assciated with a naturally ccuring cmmn cld, r frm symptms f rhinrrhea assciated with allergies. Multi-center, pen-label safety trial cnducted at 19 sites N. f patients enrlled: 268 Enrllment by trial grup: 45 in Cmmn Cld Grup; 223 in Allergy Grup ITT ppulatin: 230 N. f patient cmpleted: 214
Page: 2 f 6 This is the Diagnsis and main criteria fr inclusin: Cmmn Cld Ppulatin: Male r female at least 2 but nt lder than 5 years at screening; Diagnsis f a cmmn cld within 48 hurs f screening, with presence f swllen nasal membranes and/r presence f a fever; Capability f parent/legal guardian t administer trial drug and understand trial assessment questinnaire. Allergy Ppulatin: Male r female at least 2 but nt lder than 5 years at screening; Diagnsis f seasnal r perennial allergic rhinitis with a psitive skin r RAST test, psitive prir histry fr atpy and nasal symptms assciated with expsure t allergens; Capability f parent/legal guardian t administer trial drug and understand trial assessment questinnaire. Symptms assciated with rhinrrhea fr at least 48 hurs prir t the screening visit. Test prduct: Nasal Spray 0.06% dse: Thse with cmmn cld: tw sprays (84 mcg) per nstril t.i.d. mde f admin.: batch n.: Duratin f treatment: Thse with allergies: ne spray (42 mcg) per nstril t.i.d. Intranasal Spray Lt Numbers 256644A (363 bttles expired May 2004) and 256830A (10 bttles, expired June 2004) Thse with cmmn cld: 4 days Thse with allergies: 14 days Reference therapy: dse: mde f admin.: batch n.:
Page: 3 f 6 This is the Criteria fr evaluatin: Efficacy: Safety: Statistical methds: SUMMARY CONCLUSIONS: Primary efficacy variable: Patient s parent/legal guardian glbal assessment Secndary efficacy variable: Patient s parent/legal guardian daily assessment f symptms f rhinrrhea, nasal cngestin, and sneezing using a diary. Primary efficacy variable: adverse events Secndary efficacy variables: physican s nasal and tscpic examinatins and vital signs, physical examinatin and vital signs The primary endpint, the parent/legal guardian glbal assessment which determines the degree f symptm relief prvided by Nasal Spray 0.06%, was summarized and n statistical test was perfrmed. The secndary bjective f the trial was addressed by paired t-tests fr each f the rhinrrhea symptms (runny nse, nasal cngestin and sneezing). Fr each f the trial grups, cmparisns between the average f the daily Symptm Scres and baseline Symptm Scre were t be tested at the α=0.05 level fr the three rhinrrhea symptms. Fr this analysis, data frm all centers was cmbined. A ttal f 200 children, between the ages f 2 and 5, were t be enrlled in the trial. There were tw ppulatins: thse with rhinrrhea frm a cmmn cld (50 patients was the planned sample size, which was mdified t at least 30 patients in Amendment 2), and thse with rhinrrhea frm allergies (150 patients was the planned sample size, which was mdified t up t 170 patients in Amendment 2). This was a safety trial, and n frmal sample size calculatin was perfrmed.
Page: 4 f 6 This is the Efficacy results: This trial demnstrated that Nasal Spray 0.06% was useful, easy t use, and prvided relief fr runny nse in children 2.5 years f age with a cmmn cld r allergies. Sme imprvement was als seen in nasal cngestin and sneezing. Thirty-nine (39) f 43 parents/legal guardians f patients with a cmmn cld (91%) and 165 f 183 parents/legal guardians f patients with allergies (90%) fund Nasal Spray 0.06% either very useful r smewhat useful in treating yung children with a cmmn cld r allergies. Mrever 91% and 67% f parents/legal guardians, in the Allergy and Cmmn Cld Grups respectively, fund administratin f the nasal spray either extremely easy r very easy. Nasal Spray 0.06% shwed statistically significant imprvement in the symptm f runny nse in bth allergy and cmmn cld patients cnsistent with the knwn mechanism f an antichlinergic used in the treatment f rhinrrhea. Imprvement was als seen in nasal cngestin in bth trial grups. The change frm baseline in mean symptms scres, as assessed by the parents/legal guardians, was greatest fr runny nse in the Allergy and Cmmn Cld Grups (-1.0 and -1.6, respectively), fllwed by nasal cngestin (-0.7 and -0.8, respectively), and then sneezing (-0.2 and -0.6, respectively).
Safety results: Page: 5 f 6 This is the Overall, the use f Nasal Spray 0.06% was well tlerated in bth thse with a cmmn cld and thse with allergies. There were n deaths r serius adverse events in this trial and nly ne (0.5%) patient in the Cmmn Cld Grup and five (2.7%) patients in the Allergy Grup discntinued the trial because f an AE. Of these nly ne patient had an AE (epistaxis) that was cnsidered related t trial drug. There were 78 (33.9%) patients reprting a ttal f 142 AEs. Of these, 12 (27.9%) patients were in the Cmmn Cld Grup and 66 (35.3%) were in the Allergy Grup. The mst cmmn AEs reprted by the patients in the Cmmn Cld Grup were epistaxis, titis media, upper respiratry tract infectin, and fever. The mst cmmn AEs reprted by the patients in the Allergy Grup were fever, cughing, epistaxis, and titis media. There were n ptentially systemic antichlinergic adverse events reprted in either treatment grup. Nne f the AEs listed in these patients were cnsidered t represent previusly unsuspected r imprtant AEs if Nasal Spray 0.06%. Results f the nasal examinatins, perfrmed by the investigatrs, demnstrated that intranasal use f Nasal Spray 0.06% had n detrimental effect n the nasal mucsa. Indeed, imprvement was seen in mucsal clr, mucsal edema and rhinrrhea in bth trial grups. There was als n evidence that treatment with Nasal Spray 0.06% resulted in any apparent changes in vital sign evaluatins. Overall, Nasal Spray 0.06%, 84 mcg/nstril t.i.d. in children 2-5 years f age with cmmn clds, and 42 mcg/nstril t.i.d. in children 2-5 years f age with allergies was shwn t be safe.
Page: 6 f 6 This is the Cnclusins: Nasal Spray 0.06% was useful, easy t use, and prvided relief fr symptms f runny nse, stuffy nse, and sneezing in children 2-5 years f age with a cmmn cld r allergies. Nasal Spray 0.06% had n detrimental effect n nasal mucsa. The incidence f nasal adverse events was lw with six patients in the Cmmn Cld Grup and 11 patients in the Allergy Grup (ttal f 17 patients r 7.4%) reprting nasal AEs. The incidence f AEs leading t trial withdrawal was very lw with ne patient in the Cmmn Cld Grup and five patients in the Allergy Grup (ttal f six r 2.6%) discntinuing because f AEs. Nne f these AEs were cnsidered t represent previus unsuspected r imprtant Nasal Spray 0.06%. Nasal Spray 0.06% did nt cause any changes in vital signs.