Which methodologies were tested?

PrOACT-URL Framework BRAT Framework MCDA (Deterministic) SMAA PSM using BRR SBRAM Appendix-Data tables

Appendix-Data tables

Table 5: Efficacy AECB

Drug Treatment N n Comparator Treatment N n Efficacy parameter
A3003 Phase III-randomised , double-blind, comparative Telithromycin 800mg sid for 5 days 115 99 Amoxicillin-clavulanic acid 112 92 Cure/failure - PPc
A3007 Phase III-randomised , double-blind, comparative Telithromycin 800mg sid for 5 days 140 121 Cefuroxime 142 118 Cure/failure - PPc
A3013 Phase III-randomised , double-blind, comparative Telithromycin 800mg sid for 5 days 225 193 Clarithromycin 231 206 Cure/failure - PPc
Phase IV Telithromycin 800mg sid for 5 days 177 23 Azithromycin 106 30 PERSp at TOC-mITT population
Cefuroxime 130 17

PPc-per protocol analysis fo post-therapy/toc (test of cure) of clinical outcome

sid-once daily, bid-twice daily, tid-tree times daily

*Study terminated early

Table 6: Safety AECB

N TEAEs SAEs Hepatic adverse events Cardiac adverse event Visual adverse events Syncope
Drug Comp Drug Comp Drug Comp Drug Comp Drug Comp Drug Comp Drug Comp
Polled data from phase III trials 609 626 248 301 13 16 9 12 1 3 1 2 1 0
Polled data from phase IV trials 2132 2802 323 321 32 28 1 0 - - 9 4 4 1

In addition four controlled Phase IV (on mentioned I table above) studies confirmed the clinical efficacy of telithromycin for the treatment of AECB in Adults.

Table 7: Efficacy TP

Drug Treatment N n Comparator Treatment N n Efficacy parameter
A3004 Phase III-randomised , double-blind, comparative Telithromycin 800mg sid for 5 days 115 97 Penicillin 500mg tid, 10 days 119 106 Cure/failure - PP
A3008 Phase III-randomised , double-blind, comparative Telithromycin 800mg sid for 5 days 150 137 Clarithromycin 250mg tid, 10 days 135 119 Cure/failure - PP

PP-per protocol analysis of post-therapy/toc (test of cure) of bacteriological outcome

sid-once daily, bid-twice daily, tid-tree times daily

*Study terminated early

Table 8: Safety TP

N TEAEs SAEs Hepatic adverse events Cardiac adverse event Visual adverse events Syncope
Drug Comp Drug Comp Drug Comp Drug Comp Drug Comp Drug Comp Drug Comp
Polled data from phase III trials 427 424 224 200 5 5 7 12 0 0 9 0 0 0

Table 9: Efficacy ABS

Drug Treatment N n Comparator Treatment N n Efficacy parameter
A3002 Phase III-randomised , double-blind, comparative Telithromycin 800mg sid for 5 days 123 112 telithromycin 800mg sid, 10 days 133 102 Cure/failure - PPc
A3005 Phase III-randomised , double-blind, comparative Telithromycin 800mg sid for 5 days 146 110 Amoxicillin/clavulanic acid 500mg/125 mg tid, 10 days 137 102 Cure/failure - PPc
A3011 Phase III-randomised , double-blind, comparative Telithromycin 800mg sid for 5 days 189 161 Cefuroxime axetil 89 73 Cure/failure - PPc

PPc-per protocol analysis of post-therapy/toc (test of cure) of clinical outcome

sid-once daily, bid-twice daily, tid-tree times daily

*Study terminated early

Table 8: Safety TP

N TEAEs SAEs Hepatic adverse events Cardiac adverse event Visual adverse events Syncope
Drug Comp Drug Comp Drug Comp Drug Comp Drug Comp Drug Comp Drug Comp
Pooled data from phase III trials 750 366 392 182 7 2 13 2 0 1 9 3 0 1
Pooled data from phase III open -label 333 - 114 - 4 - 14 - 2 - 1 - - -
Pooled data from phase IV trials 565 579 149 145 2 2 04 1 - - 7 1 0 0

Additional 3 phase IV randomized controlled studies performed in the ABS indication in adults showed that telithromycin was non-inferior to moxifloxacin, high dosage amoxicillin/clavulanic acid (875/125 mg bid) and amoxicillin/clavulanic acid (500/125mg tid). Time to symptom resolution was shown to be similar between telithromycin and moxifloxacin, and shorter with telithromycin than high dose amoxicillin/clavulanic acid (median time 4.0 vs. 5.0 days)

Table 11: Efficacy CAP

Study Drug Treatment N n Comparator Treatment N n Efficacy parameter
A3001 Phase III, randomised, double-blinde, comparative Telithromycin 800mg sid, 10 days 149 141 Amoxicillin 1000mg tid, 10 day 152 137 Cure/failure-PPc
A3006 Phase III, randomised, double-blinde, comparative Telithromycin 800mg sid, 10 days 162 143 Clarithromycin 500mg bid, 10 days 156 138
A3009* Phase III, randomised, double-blinde, comparative Telithromycin 800mg sid, 7-10 days 80 72 Trovafloxacin 200mg sid, 7-10 days 86 81
A4003 Phase III, randomised, double-blinde, comparative Telithromycin 800mg sid, 7 days 159 142 Clarithromycin 146 134
A3000 Phase III, open-lable uncontroled Telithromycin 800mg sid, 5-7 days 197 183 - - - -
A3009OL Phase III, open-lable uncontroled Telithromycin 187 175 - - - -
A3010 Phase III, open-lable uncontroled Telithromycin 357 332 - - - -
A3012 Phase III, open-lable uncontroled Telithromycin 723 646 - - - -
A4015 Phase IV Telithromycin 242 208 Locally prescribed regimen 240 189

PPc-per protocol analysis fo post-therapy/toc (test of cure) of clinical outcome

sid-once daily, bid-twice daily, tid-tree times daily

*Study terminated early

Table 12: Safety Cap

N TEAEs SAEs Hepatic adverse events Cardiac adverse event Visual adverse events Syncope
Drug Comp Drug Comp Drug Comp Drug Comp Drug Comp Drug Comp Drug Comp
Pooled data from phase III trials 916 723 484 352 34 38 45 33 4 3 11 4 2 2
Polled data from phase III open -lable 1745 - 65 - 4 - 50 - 1 - 9 - - -
Polled data from phase IV trials 404 398 168 179 27 333 12 13 - - 3 1 0 1

Additional 3 phase IV studies confirmed the high clinical efficacy of telithromycin in CAP with trend for superior efficacy in on study (A4015)