Malcolm R. Sears1*, Anders Ottosson2, Finn Radner2 and Samy Suissa3
Affiliations:
1Firestone Institute for Respiratory Health, St Joseph’s Healthcare and McMasterUniversity, Hamilton, ON, Canada
2AstraZeneca R&D, Lund, Sweden
3Dept of Epidemiology and Biostatistics, McGillUniversity, Montreal, QC, Canada
*Corresponding author:
Malcolm R. Sears
Firestone Institute for Respiratory Health
St Joseph’s Healthcare and McMasterUniversity
Hamilton, Ontario, Canada
Email address:
Tel: +1-905-522-1155 ext 33286
Fax: + 1-905-521-6132
Short title: / Safety of formoterol in asthma trials
Word count: / 5369 (excl. abstract, refs, fig/tables and legends)
ONLINE SUPPLEMENT
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TABLE E-1. DETAILS OF CLINICAL TRIALS INCLUDED IN THE MAIN AND THE SUPPLEMENTARY ANALYSISStudy code / Included in the main analysis? / Reason for omission from primary analysis / Duration / Comparators / Baseline ICS use, % / Age range, years / Number of patients evaluable for safety / Blinded or open label / Design / Maintenance or as-needed use or adjustable dosing / Comments
Formoterol Turbuhaler trials
37-3002 / N / Duration / 1 month / PLAC / 88 / 18–81 / 221 / DB / P / M
37-3006 / Y / 3 months / PLAC; TERB / 89 / 18–82 / 343 / DB / P / M
37-3026 / Y / 3 months / PLAC; TERB / 86 / 18–79 / 396 / DB / P / M
SD-037-0003 / Y / 3 months / PLAC / 83 / 6–17 / 248 / DB / P / M
DC-037-0002 / Y / 3 months / PLAC / 100 / 6–11 / 301 / DB / P / M
37-3008 / Y / 6months / PLAC / 100 / 18–75 / 239 / DB / P / M
37-3018 / Y / 12 months / BUD / Na / 17–70 / 853 / DB / P / M
37-3041 / Y / 12 months / BUD / Na / 19–69 / 60 / DB / P / M
SD-037-0345 / Y / 12 months / PLAC; BUD / Na / 11–82 / 1,970 / DB / P / M
37-3010 / N / Duration / >24 months / None / 94 / 21–82 / 187 / O / P / M / 18 g vs. 36 g
37-3015 / N / Duration / >24 months / None / 100 / 18–71 / 13 / O / O / M / No ref treatment
SD-037-0175 / Y / 3 months / TERB / 100 / 18–75 / 357 / DB / P / M and AN
SD-037-0123 / Y / 3 months / TERB / 100 / 18–75 / 362 / DB / P / AN
SD-037-0695 / Y / 6 months / TERB / 93 / 5–17 / 552 / DB / P / AN
SD-037-0714 / Y / 12 months / TERB / 95 / 6–75 / 455 / DB / P / AN
SD-037-0716 / Y / 12 months / TERB / 0 / 6–87 / 674 / DB / P / AN
SD-037-0699 / Y / 6 months / SALB / 67 / 4–91 / 17,862 / O / P / AN
SD-037-0739 / Y / 6 months / FORM / 100 / 12–78 / 320 / O / P / AN vs. M + AN
BU-543-0681 part A / N / Duration / 1 month / BUD / 100 / 12–83 / 663 / DB / P / M
BU-543-0681 part B / N / Follow-up / 5 months / BUD / 100 / 12–83 / Follow-up / DB / P / M
MA-037-0001 / N / Not suitable / 3 months / BUD / 100 / 18–66 / 225 / DB/O / P / M
BU-037-0004 / Y / 3 months / SALM / 100 / 6–17 / 156 / O / P / M
DC-037-0001 / Y* / 3 months / SALM; SALB / 100 / 18–81 / 372 / O / P / M
BU-543-0677 / N / Duration / 1 month / BUD + FORM / 100 / 19–76 / 236 / O / P / M and AN
37-3005 / N / Design / 1 day / FORM; PLAC / Na / 26–65 / 31 / DB / C / na
37-3007 / N / Design / 14 days / FORM / Na / 18–73 / 66 / DB / C / na
37-3011 / N / Design / 14 days / FORM / Na / 15–76 / 66 / DB / C / na
37-3019 / N / Design / 1 day / SALB; PLAC / Na / 20–56 / 13 / DB / C / na
37-3025 / N / Design / 1 day / FORM; PLAC / Na / 23–61 / 28 / DB / C / na
37-3027 / N / Duration / 7 days / FORM; PLAC / Na / 18–59 / 165 / DB / P / na
37-3028 / N / Design / 1 day / SALM; PLAC / Na / 20–69 / 28 / DB / C / na
37-3040 / N / Design / 21 days / SALM / Na / 21–66 / 39 / DB / C / na
SD-037-0002 / N / Design / 1 day / SALM; PLAC / Na / 7–17 / 65 / DB / O / na
SD-037-0010 / N / Duration / 1 day / TERB / Na / 20–64 / 48 / DB / P / na / Acute bronchoconstriction
SD-037-0011 / N / Duration / 14 days / TERB; PLAC / Na / 18–65 / 72 / DB / P / na
SD-037-0012 / N / Design / 1 day / TERB; PLAC / Na / 19–53 / 33 / DB / C / na
SD-037-0013 / N / Design / 3 days / TERB / Na / 38–73 / 28 / DB / C / na / High-dose tolerability
SD-037-0068 / N / Design / 1 day / SALB; PLAC / Na / 20–64 / 29 / DB / C / na / High-dose tolerability
SD-037-0149 / N / Design / 1 day / TERB; PLAC / Na / 8–17 / 27 / DB / C / na
SD-037-0287 / N / Design / 1 day / FORM; PLAC / Na / 20–70 / 60 / DB / C / na
SD-037-0361 / N / Design / 1 day / SALB; PLAC / Na / 18–64 / 36 / DB / C / na
SD-037-0657 / N / Design / 1 day / FORM; PLAC / Na / 18–67 / 23 / DB / C / na
SD-037-0684 / N / Design / 1 day / FORM; PLAC / Na / 20–81 / 46 / DB / C / na
SD-037-0718 / N / Duration / 1 day / SALB / Na / 18–67 / 88 / DB / P / na / Acute bronchoconstriction
SD-037-0724 / N / Duration / 1 day / SALB / Na / 18–69 / 78 / DB / P / na / Acute bronchoconstriction
SD-037-0738 / N / Design / 1 day / TERB; PLAC / Na / 6–11 / 20 / DB / C / na / High-dose tolerability
SD-037-0744 / N / Design / 1 day / SALB; PLAC / Na / 21–66 / 26 / DB / C / na
SD-037-0745 / N / Duration / 1 month / PLAC / 100 / 20–84 / 282 / DB / P / M
SD-004-0216 / N / Duration / 2 months / BUD; Zafirlukast / Na / 12–72 / 352 / DB / P / na
Formoterol pMDI trials
SD-037-0288 / N / Incomplete / 1 year / FORM / Na / 435 / DB / P / M / Abbreviated CSR
SD-037-0344 / N / Incomplete / 3 months / FORM; PLAC / Na / 639 / DB / P / M / Abbreviated CSR
SD-037-0737 / N / Design / 1 day / SALB; PLAC / Na / 18–69 / 30 / DB / C / na
D5126C00017 / N / Design / 1 day / SALB / Na / 1–6 / 34 / SB / P / na
Formoterol/budesonide Turbuhaler trials
SD-039-0348 / Y / 3 months / BUD / Na / 18–78 / 467 / DB / P / M
SD-039-0349 / Y / 3 months / BUD; BUD + FORM / Na / 18–78 / 362 / DB / P / M
SD-039-0353 / Y / 3 months / BUD / Na / 4–17 / 286 / DB / P / M
SD-039-0618 / Y / 3 months / FLUT / Na / 17–75 / 344 / DB / P / M
SD-039-0665 / Y / 3 months / BUD / Na / 18–80 / 616 / DB / P / M
SD-039-0666 / Y / 3 months / BUD / Na / 18–78 / 523 / DB / P / M
SD-039-0688 / Y / 3 months / BUD; BUD + FORM / Na / 4–11 / 630 / DB / P / M
SD-039-0671 / N / Duration / 2 weeks / FLUT / Na / 17–75 / 438 / DB / P / M
SD-039-0714 / Y / 3 months / BUD / Na / 11–17 / 270 / DB / P / M
SD-039-0689 / Y / 3/6 months / BUD; BUD + FORM / Na / 12–79 / 456 / DB / P / M / 3 months for BUD treatment
SD-039-0664 / Y / 6/12 months / BUD + FORM / Na / 18–81 / 585/289 / O / P / M
SD-039-0667 / Y / 6 months / BUD + TERB prn / Na / 11–79 / 696 / DB / P / M + AN
SD-039-0668 / Y / 12 months / BUD + TERB prn / Na / 11–80 / 1,890 / DB / P / M + AN
SD-039-0673 / Y / 12 months / BUD/FORM + TERB prn; BUD + TERB prn / Na / 4–79 / 2,753 / DB / P / M + AN
SD-039-0734 / Y / 12 months / BUD/FORM + FORM prn; BUD/FORM + TERB prn / Na / 12–89 / 3,382 / DB / P / M + AN
SD-039-0735 / Y* / 6 months / BUD/FORM + TERB prn; SALM/FLUT + TERB prn / Na / 11–83 / 3,321 / DB / P / M + AN
SD-039-0691 / Y* / 12 months / SALM/FLUT + SALB prn / Na / 12–84 / 2,135 / O / P / M + AN
SD-039-0686 / Y* / 6 months / BUD/FORM (fixed maintenance dose); SALM/FLUT / Na / 12–85 / 658 / DB/O / P / M; AMD
D5890C00002 / Y* / 6 months / SALM/FLUT + SALB prn / Na / 12–80 / 2,304 / DB / P / M + AN
DC-039-0002 / N / Duration / 1 month / BUD + FORM / Na / 18–75 / 237 / DB / P / M
CN-039-0001 / Y / 3 months / BUD + FORM / Na / 14–79 / 320 / O / P / M
BA-039-0001 / Y / 4 months / BUD / Na / 19–81 / 133 / DB / P / AMD
BE-039-0001 / Y / 4 months / BUD/FORM bid / Na / 12–81 / 980 / O / P / AMD
DC-039-0001 / Y / 5 months / BUD/FORM bid / Na / 12–96 / 995 / O / P / AMD
AD-039-0001 / Y / 6 months / BUD/FORM bid / Na / 18–80 / 796 / O / P / AMD
MA-SYM-0001 / Y / 3 months / BUD/FORM bid / Na / 11–82 / 537 / O / P / AMD
IE-SYM-0001 / Y / 3 months / BUD/FORM bid / Na / 17–82 / 203 / O / P / AMD
CI-SYM-0001 / Y / 3 months / BUD/FORM bid / Na / 6–87 / 2,358 / O / P / AMD
BU-039-0004 / Y / 3 months / BUD/FORM bid / Na / 18–87 / 1,553 / O / P / AMD
CF-039-0001 / Y / 3 months / BUD/FORM bid / Na / 12–100 / 873 / O / P / AMD
CF-039-0002 / Y / 3 months / BUD/FORM bid / Na / 12–93 / 2,068 / O / P / AMD
BG-SYM-0003 / Y / 3 months / BUD/FORM bid / Na / 16–87 / 3,297 / O / P / AMD
PL-039-0001 / Y / 3 months / BUD/FORM bid / Na / 10–53 / 1,606 / O / P / AMD
LD-039-0001 / Y / 6 months / BUD/FORM bid / Na / 12–83 / 1,034 / O / P / AMD
BS-039-0002 / Y / 3 months / BUD/FORM bid / Na / 12–78 / 142 / O / P / AMD
LD-039-0003 / Y / 6 months / BUD/FORM bid + FORM prn / Na / 6–82 / 491 / O / P / M + AN
AF-039-0001 / Y / 6 months / FORM prn / Na / 15–63 / 92 / DB / P / AN
39-3002 / N / Design / 28 days / FORM; BUD / Na / 22–57 / 20 / DB / C / na
D5890C00007 / N / Design / 1 day / SALB; PLAC / Na / 18–50 / 32 / DB / C / na
SD-039-0367 / N / Design / 1 day / FORM; PLAC / Na / 21–59 / 15 / DB / C / na / High-dose tolerability
SD-039-0617 / N / Design / 1 day / FLUT/SALM; PLAC / Na / 28–73 / 30 / DB / C / na
SD-039-0678 / N / Design / 1 day / FLUT/SALM; PLAC / Na / 22–48 / 27 / DB / C / na
SD-039-0685 / N / Design / 3 days / FLUT/SALM; PLAC / Na / 18–65 / 43 / DB / C / na
SD-039-0693 / N / Duration / 1 day / FORM / Na / 12–78 / 115 / DB / P / na / Acute bronchoconstriction
SD-039-0702 / N / Duration / 1 day / SALB / Na / 13–80 / 103 / DB / P / na / Acute bronchoconstriction
Formoterol/budesonide pMDI trials
D5896C00001 / Y / 3 months / BUD / Na / 12–79 / 618 / DB / P / M
SD-039-0681 / Y / 3 months / BUD; BUD/FORM / Na / 11–79 / 679 / DB / P / M
SD-039-0682 / Y / 3 months / BUD; BUD/FORM / Na / 6–11 / 622 / DB / P / M
SD-039-0716 / Y / 3 months / BUD; PLAC; FORM / Na / 6–78 / 511 / DB / P / M / ICS-free patients
SD-039-0717 / Y / 3 months / BUD; PLAC; FORM; BUD + FORM / Na / 12–87 / 596 / DB / P / M / ICS-free patients
SD-039-0718 / Y / 3 months / BUD; FORM / Na / 6–15 / 411 / DB / P / M / ICS-free patients
SD-039-0725 / Y / 3 months / BUD / Na / 6–15 / 521 / DB / P / M
SD-039-0726 / Y / 3 months / BUD; PLAC / Na / 16–79 / 751 / DB / P / M
SD-039-0728 / Y / 12 months / BUD / Na / 12–81 / 708 / DB / P / M
SD-039-0715 / Y / 12 months / BUD/FORM / Na / 12–85 / 673 / O / P / M
SD-039-0719 / Y / 6 months / BUD / Na / 6–11 / 186 / O / P / M
D5896C00005 / Y* / 7 months / FLUT/SALM / Na / 12-87 / 1,221 / O / P / M
D5896C00010 / N / Design / 1 day / FORM; BUD / Na / 22–63 / 29 / O / C / na / High-dose tolerability
D5896C00011 / N / Design / 7 days / BUD + FORM / Na / 21–64 / 26 / O / P / na
D5896C00013 / N / Design / 1 day / BUD + FORM / Na / 6–11 / 24 / O / C / na
SD-039-0729 / N / Design / 1 day / BUD; FORM / Na / 18–80 / 201 / O / C / na
SD-039-0732 / N / Design / 1 day / SALB; FLUT/SALM; PLAC / Na / 18–69 / 55 / SB / C / na
SD-039-0733 / N / Design / 1 day / SALB; FLUT/SALM; PLAC / Na / 18–68 / 54 / SB / C / na
SD-039-0738 / N / Design / 1 day / BUD + FORM / Na / 43–67 / 30 / O / C / na
SD-039-0743 / N / Duration / 6 weeks / BUD + FORM / Na / 6–84 / 283 / O / M / na
SUM / 117 trials / 78,338
* In this trial, patients exposed to salmeterol were removed from the main analysis but included in the supplementary analysis.
AMD = adjustable maintenance dosing; AN = as-needed use; bid = twice daily; BUD = budesonide; C = cross-over; CSR = clinical study report; DB = double blind; FLUT = fluticasone; FORM = formoterol; ICS = inhaled corticosteroid; M = maintenance treatment; N = not included; na = not applicable; O = open label; P = parallel; PLAC = placebo; pMDI = pressurized metered-dose inhaler; prn = as needed; SALB = salbutamol; SALM = salmeterol; SB = single blind; TERB = terbutaline; Y = included.
TABLE E-2. STUDY TITLE AND PUBLICATION STATUS FOR CLINICAL TRIALS INCLUDED IN THE MAIN AND THE SUPPLEMENTARY ANALYSISStudy code / Included in the main analysis? / Study title / Publication status
Formoterol Turbuhaler trials, double-blind, parallel-group with twice-daily treatment
37-3002 / N / A COMPARISON OF THE EFFICACY OF THREE DIFFERENT DOSES OF A LONG ACTING B-AGONIST, D2522, AND PLACEBO INHALED VIA TURBUHALER IN ASTHMATIC PATIENTS / Schreurs AJ, Sinninghe Damste HE, de Graaff CS, Greefhorst AP. A dose–response study with formoterol Turbuhaler as maintenance therapy in asthmatic patients. Eur Respir J 1996; 9: 1678-1683.
37-3006 / Y / A COMPARISON OF THE EFFICACY OF INHALED D 2522 VERSUS TERBUTALINE AND PLACEBO ADMINISTERED VIA TURBUHALER IN PATIENTS WITH ASTHMA / Ekström T, Ringdal N, Tukiainen P, Runnerström E, Soliman S. A 3-month comparison of formoterol with terbutaline via Turbuhaler. A placebo-controlled study. Ann Allergy Asthma Immunol 1998; 81: 225-230.
37-3026 / Y / FORMOTEROL 6 µG B.I.D VIA TURBUHALER FOR 3 MONTHS COMPARED WITH TERBUTALINE AND PLACEBO IN PATIENTS WITH ASTHMA / Ekström T, Ringdal N, Sobradillo V, Runnerström E, Soliman S. Low-dose formoterol Turbuhaler (Oxis) bid, a 3-month placebo-controlled comparison with terbutaline (q.i.d.). Respir Med 1998b; 92: 1040-1045.
SD-037-0003 / Y / A 3-MONTH, PLACEBO-CONTROLLED EFFICACY STUDY OF FORMOTEROL TURBUHALER 4.5 µG AND 9 µG B.I.D. (CORRESPONDING TO THE METERED DOSES 6 µG AND 12 µG, RESPECTIVELY) IN ASTHMATIC CHILDREN AGED 6 TO 17 YEARS / von Berg A, Papageorgiou Saxoni F, Wille S, Carrillo T, Kattamis C, Helms PJ. Efficacy and tolerability of formoterol Turbuhaler® in children. Int J Clin Pract 2003; 57: 852-856.
DC-037-0002 / Y / A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE EFFICACY, TOLERABILITY, AND COST-EFFECTIVENESS OF FORMOTEROL TURBUHALER 6 µG AND 12 µG B.I.D. IN SIX TO ELEVEN YEAR OLD CHILDREN WITH SYMPTOMATIC ASTHMA / Zimmerman B, D’Urzo A, Bérubé D. Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid treatment in children with asthma. Pediatr Pulmonol 2004; 37: 122-127.
37-3008 / Y / THE EFFICACY OF INHALED D2522, 24 µG BID, VIA TURBUHALER. A PLACEBO-CONTROLLED, RANDOMIZED, PARALLEL GROUP, LONG-TERM STUDY IN PATIENTS WITH ASTHMA USING TERBUTALINE 0.25 MG AS RESCUE MEDICATION / van der Molen T, Postma DS, Turner MO, Meyboom-de Jong B, Malo JL, Chapman K, Grossman R, de Graaff CS, Riemersma RA, Sears MR. Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. Thorax 1997; 52: 535-539.
37-3018 / Y / FORMOTEROL AND CORTICOSTEROIDS (BUDESONIDE) ESTABLISHING THERAPY. A LONG TERM PLACEBO CONTROLLED STUDY OF INHALED FORMOTEROL WITH LOW OR HIGH DOSE BUDESONIDE IN ASTHMA THERAPY / Pauwels RA, Löfdahl CG, Postma DS, Tattersfield AE, O’Byrne P, Barnes PJ, Ullman A. Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med 1997; 337: 1405-1411.
37-3041 / Y / A LONG TERM STUDY OF THE ANTI-INFLAMMATORY EFFECTS OF LOW DOSE BUDESONIDE PLUS FORMOTEROL VS. HIGH DOSE BUDESONIDE IN ASTHMA THERAPY / Kips JC, O’Connor BJ, Inman MD, Svensson K, Pauwels RA, O’Byrne PM. A long-term study of the antiinflammatory effect of low-dose budesonide plus formoterol versus high-dose budesonide in asthma Am J Respir Crit Care Med 2000; 161: 996-1001.
SD-037-0345 / Y / OXIS AND PULMICORT TURBUHALER IN THE MANAGEMENT OF ASTHMA / O’Byrne PM, Barnes PJ, Rodriguez-Roisin R, Runnerstrom E, Sandstrom T, Svensson K, Tattersfield A. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med 2001; 164: 1392-1397.
Formoterol Turbuhaler trials, open-label, uncontrolled with twice-daily treatment
37-3010 / N / A LONG-TERM OPEN SAFETY STUDY OF INHALED D2522 VIA TURBUHALER IN PATIENTS WITH ASTHMA / Data on file
37-3015 / N / A LONG-TERM OPEN SAFETY STUDY OF INHALED D2522 VIA TURBUHALER IN PATIENTS WITH ASTHMA, PREVIOUSLY INCLUDED IN STUDY 37-3011 / Data on file
Formoterol Turbuhaler trials, double-blind, parallel-group with twice-daily plus as-needed treatment
SD-037-0175 / Y / A 12-WEEK COMPARISON OF OXIS TURBUHALER (FORMOTEROL) B.I.D. AND OXIS TURBUHALER P.R.N. VERSUS OXIS TURBUHALER B.I.D. AND BRICANYL TURBUHALER (TERBUTALINE) P.R.N. IN PATIENTS WITH ASTHMA ON THERAPY WITH INHALED CORTICOSTEROIDS / Ind PW, Villasante C, Shiner RJ, Pietinalho A, Boszormenyi NG, Soliman S, Selroos O. Safety of formoterol by Turbuhaler® as reliever medication compared with terbutaline in moderate asthma. Eur Respir J 2002; 20: 859-866.
Formoterol Turbuhaler trials, double-blind, parallel-group with as-needed treatment
SD-037-0123 / Y / A 12-WEEK COMPARISON OF 4.5 µG OXIS TURBUHALER (FORMOTEROL) P.R.N. VERSUS 0.5 MG BRICANYL TURBUHALER (TERBUTALINE) P.R.N. IN ASTHMATICS ON THERAPY WITH INHALED STEROIDS / Tattersfield AE, Löfdahl C-G, Postma DS, Eivindson A, Schreurs AGM, Rasidakis A, Ekström T. Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised trial. Lancet 2001; 357: 257-261.
SD-037-0695 / Y / A 6 MONTHS COMPARISON OF THE SAFETY AND EFFICACY PROFILES OF OXIS (FORMOTEROL) TURBUHALER AS NEEDED AND BRICANYL (TERBUTALINE) TURBUHALER AS NEEDED IN CHILDREN WITH ASTHMA ON ANTI-INFLAMMATORY TREATMENT / Villa J, Kuna P, Egner J, Brander R. Safety of formoterol reliever therapy compared with terbutaline in asthmatic children taking anti-inflammatory therapy [abstract]. Eur Respir J 2002; 20 (Suppl 38): 431.
SD-037-0714 / Y / A 12-MONTH COMPARISON OF FORMOTEROL TURBUHALER AND TERBUTALINE TURBUHALER BOTH USED AS NEEDED IN PATIENTS WITH ASTHMA ON ANTI-INFLAMMATORY TREATMENT / Chuchalin A, Kasl M, Bengtsson T, Nihlen U, Rosenborg J. Formoterol used as needed in patients with intermittent or mild persistent asthma. Respir Med 2005; 99: 461-470.
SD-037-0716 / Y / A 12-MONTH COMPARISON OF FORMOTEROL TURBUHALER AND TERBUTALINE TURBUHALER BOTH USED AS NEEDED IN PATIENTS WITH ASTHMA NOT USING ANTI-INFLAMMATORY TREATMENT / Chuchalin A, Kasl M, Bengtsson T, Nihlen U, Rosenborg J. Formoterol used as needed in patients with intermittent or mild persistent asthma. Respir Med 2005; 99: 461-470.
Formoterol Turbuhaler trials, open-label, parallel-group with as-needed treatment
SD-037-0699 / Y / REAL LIFE EFFECTIVENESS OF OXIS TURBUHALER AS NEEDED IN ASTHMATIC PATIENTS DURING SIX MONTHS (RELIEF) / Pauwels RA, Sears MR, Campbell M, Villasante C, Huang S, Lindh A, Petermann W, Aubier M, Schwabe G, Bengtsson T. Formoterol as relief medication in asthma: a worldwide safety and effectiveness trial. Eur Respir J 2003; 22: 787-794.
SD-037-0739 / Y / A 6 MONTHS, RANDOMISED, OPEN, PARALLEL GROUP, MULTICETNRE STUDY TO EXAMINE EFFICACY AND SAFETY OF AS NEEDED VERSUS MAINTENANCE USE OF OXIS 9 MCG IN SUBJECTS WELL CONTROLLED ON MAINTENANCE TREATMENT WITH INHALED GCS AND LONG ACTING B2-AGONISTS / Data on file
Formoterol Turbuhaler trials, performed by local marketing companies
BU-543-0681 part A & B / N / EFORMOTEROL IN THE MANAGEMENT OF MILD ASTHMA - EFORMOTEROL TURBUHALER WITH BUDESONIDE TURBUHALER: FLOW / Price D, Dutchman D, Mawson A, Bodalia B, Duggan S, Todd P. Early asthma control and maintenance with eformoterol following reduction of inhaled corticosteroid dose. Thorax 2002; 57: 791-798.
MA-037-0001 / N / THE EFFICACY OF PULMICORT® TURBUHALER WITH AND WITHOUT OXIS® TURBUHALERCOMPARED TO CURRENT NON-STEROID THERAPY IN PATIENTS WITH MILD TO MODERATE ASTHMA IN RUSSIA (EPOCH) / Chuchalin AG, Ovcharenko SI, Goriachkina LA, Sidorenko IV, Tsoi AN. The safety and efficacy of formoterol (Oxis®) Turbuhaler® plus budesonide (Pulmicort®) Turbuhaler in mild to moderate asthma: a comparison with budesonide Turbuhaler alone and current non-corticosteroid therapy in Russia. Int J Clin Pract 2002; 56: 15-20.
BU-037-0004 / Y / EFORMOTEROL VS. SALMETEROL: REDUCTION IN SHORT-ACTING BRONCHODILATOR USAGE IN ASTHMATIC CHILDREN TREATED WITH INHALED STEROIDS: FACT / Everden P, Campbell M, Harnden C, McGoldrick H, Bodalia B, Manion V, Reynia S. Eformoterol Turbohaler® compared with salmeterol by dry powder inhaler in asthmatic children not controlled on inhaled corticosteroids. Pediatr Allergy Immunol 2004; 15: 40-47.
DC-037-0001 / Y* / A CLINICAL AND ECONOMIC COMPARISON OF FORMOTEROL TURBUHALER® VERSUS SALMETEROL AND SALBUTAMOL PMDI IN ASTHMATIC PATIENTS NOT WELL-CONTROLLED ON INHALED STEROID THERAPY / Mintz S, Orcheson L, Wang E. Clinical and economic evaluation of formoterol Turbuhaler (FORM) compared with salmeterol (SALM) and salbutamol (SALB) in moderate to severe asthma. J Allergy Clin Immunol 1999; 103: S74-75.
BU-543-0677 / N / DOES EFORMOTEROL TURBOHALER ALLOW A REDUCTION IN THE NUMBER OF DRUGS USED IN ASTHMA MANAGEMENT? A STUDY COMPARING BUDESONIDE AND EFORMOTEROL TURBUHALER BID WITH TERBUTALINE TURBUHALER PRN VERSUS BUDESONIDE AND EFORMOTEROL TURBUHALER BID WITH EFORMOTEROL TURBUHALER PRN / O’Connor BJ, McSorley LC, Turbitt ML. Does treatment with eformoterol Turbohaler prn allow a reduction in the number of inhalers used to treat moderate to severe asthma? Am J Respir Crit Care Med 2000; 161: A191.
Formoterol Turbuhaler trials, other
37-3005 / N / AN EVALUATION OF EFFICACY, TOLERABILITY AND DURATION OF ACTION OF INHALED D2522 AFTER SINGLE DOSE ADMINISTRATIONS TO ASTHMATICS / Data on file
37-3007 / N / A COMPARISON OF THE EFFICACY OF INHALED D2522, 24 µG B.I.D.,VIA TURBUHALER, AND FORMOTEROL, 24 µG B.I.D., CFC INHALER IN PATIENTS WITH ASTHMA / Data on file
37-3011 / N / A COMPARISON OF EFFICACY OF INHALED D-2522, 12 µG B.I.D., VIA TURBUHALER AND FORMOTEROL, 12 µG B.I.D., CFC INHALER IN PATIENTS WITH ASTHMA / Data on file
37-3019 / N / TOLERABILITY OF HIGH DOSE FORMOTEROL TURBUHALER VS. HIGH DOSE SALBUTAMOL PMDI IN ASTHMATIC PATIENTS DURING REGULAR TWICE DAILY TREATMENT WITH FORMOTEROL TURBUHALER 12 µG / Data on file
37-3025 / N / AN EVALUATION OF THE EFFICACY AND DURATION OF ACTION OF D 2522 TURBUHALER (3, 6, 12 AND 24 µG) AND FORMOTEROL PRESSURIZED METERED DOSE INHALER (12 µG) AFTER SINGLE DOSE ADMINISTRATIONS TO ASTHMATICS / Data on file
37-3027 / N / A DOUBLE-BLIND, RANDOMIZED, PARALLEL GROUP, PLACEBO-CONTROLLED, DOSE-RESPONSE STUDY OF FORMOTEROL TURBUHALER, 6, 12 AND 24 µG, ADMINISTRATED TWICE DAILY IN PATIENTS WITH ASTHMA / Data on file
37-3028 / N / AN EVALUATION OF THE EFFICACY AND DURATION OF ACTION OF FORMOTEROL TURBUHALER (6,12 AND 24 µG) AS COMPARED WITH SALMETEROL (SERVENT) DISKHALER (50 µG) AFTER SINGLE DOSE ADMINISTRATIONS TO ASTHMATICS / Data on file
37-3040 / N / PROTECTIVE EFFECT OF SALBUTAMOL AGAINST METHACHOLINE BROMIDE IN ASTHMATIC PATIENTS PRE-TREATED WITH FORMOTEROL TURBUHALER OR SALMETEROL DISKHALER / Data on file
SD-037-0002 / N / EFFICACY AND TOLERABILITY OF SINGLE DOSES OF FORMOTEROL TURBUHALER 6, 12, 24, 48 µG COMPARED TO SALMETEROL DISKHALER 50 µG AND PLACEBO IN CHILDREN WITH BRONCHIAL ASTHMA / Pohunek P, Matulka M, Rybnícek O, Kopriva F, Honomichlová H, Svobodová T. Dose-related efficacy and safety of formoterol (Oxis®) Turbuhaler®compared with salmeterol Diskhaler® in children with asthma. Pediatr Allergy Immunol 2004; 15: 32-39.
SD-037-0010 / N / SAFETY AND EFFICACY OF FORMOTEROL TURBUHALER ADMINISTERED TO ASTHMA/COPD PATIENTS WITH ACUTE BRONCHIAL OBSTRUCTION. A COMPARISON WITH TERBUTALINE (BRICANYL) TURBUHALER TREATMENT / Malolepszy J, Böszörményi Nagy G, Selroos O, Larsson P, Brander R. Safety of formoterol Turbuhaler® at cumulative dose of 90 mcg in patients with acute bronchial obstruction. Eur Respir J 2001; 18: 928-934.
SD-037-0011 / N / PROTECTION AGAINST METHACHOLINE-INDUCED BRONCHOCONSTRICTION AFTER FIRST DOSE AND AFTER 14 DAYS' TREATMENT: A COMPARISON OF FORMOTEROL TURBUHALER 12 µG O.D., 6 µG B.I.D., 24 µG B.I.D., BRICANYL TURBUHALER 0.5 MG Q.I.D. AND PLACEBO IN PATIENTS WITH ASTHMA / Lipworth J, Tan S, Devlin M, Aiken T, Baker R, Hendrick D. Effects of treatment with formoterol on bronchoprotection against methacholine.Am J Med 1998; 104: 431-438.
SD-037-0012 / N / DURATION OF PROTECTION OF FORMOTEROL 12 µG AGAINST EXERCISE-INDUCED BRONCHOCONSTRICTION, COMPARED WITH TERBUTALINE 0.5 MG AND PLACEBO, DURING REGULAR TREATMENT WITH FORMOTEROL TURBUHALER 12 µG B.I.D. IN ADULT ASTHMATICS / Vilsvik J, Ankerst J, Palmqvist M, Persson G, Schaanning J, Schwabe G, Johansson Å. Protection against cold air and exercise-induced bronchoconstriction while on regular treatment with Oxis. Respir Med 2001; 95(6): 484-490.
SD-037-0013 / N / TOLERABITITY OF HIGH DOSES OF FORMOTEROL TURBUHALER DURING THREE DAYS COMPARED WITH 6 AND 10 MG TERBUTALINE TURBUHALER. A DOUBLE-BLIND, CROSS-OVER, RANDOMIZED STUDY IN PATIENTS WITH ASTHMA / Tötterman KJ, Huhti L, Sutinen E, Backman R, Pientinalho A, Falck M, Larsson P, Selroos O. Tolerability to high doses of formoterol and terbutaline via Turbuhaler for 3 days in stable asthmatic patients.Eur Respir J 1998; 12(3): 573-579.
SD-037-0068 / N / ON THE RELATIVE THERAPEUTIC INDEX BETWEEN FORMOTEROL TURBUHALER AND SALBUTAMOL PMDI IN ASTHMATIC PATIENTS / Rosenborg J, Larsson P, Rott Z, Böcskei C, Poczi M, Juhász G. Relative therapeutic index between inhaled formoterol and salbutamol in asthma patients. Respir Med 2002; 96(6): 412-417.
SD-037-0149 / N / PROTECTIVE EFFECT OF SINGLE DOSES OF FORMOTEROL TURBUHALER 4.5µG AND 9 µG (CORRESPONDING TO THE METERED DOSES 6 µG AND 12 µG, RESPECTIVELY) COMPARED WITH BRICANYL TURBUHALER 0.5 MG AND PLACEBO IN CHILDREN WITH EXERCISE INDUCED BRONCHOCONSTRICTION / Grönneröd TA, von Berg A, Schwabe G, Soliman S. Formoterol via Turbuhaler® gave better protection than terbutaline against repeated exercise challenge for up to 12 hours in children and adolescents.Respir Med 2000; 94(7): 661-667.
SD-037-0287 / N / A DOUBLE BLIND, RANDOMIZED, PLACEBO CONTROLLED CROSS-OVER STUDY TO COMPARE THE BRONCHODILATORY EFFECT OF FORMOTEROL INHALED VIA TWO DIFFERENT TURBUHALER DEVICES / Data on file
SD-037-0361 / N / THE BRONCHODILATING EFFECT DURING 30 MINUTES OF TWO DOSES OF FORMOTEROL TURBUHALER COMPARED TO TWO DOSES OF SALBUTAMOL PMDI AND PLACEBO / Seberova E, Andersson A. Oxis (formoterol given by Turbuhaler) showed as rapid an onset of action as salbutamol given by a pMDI.Respir Med 2000; 94(6): 607-611.
SD-037-0657 / N / A PLACEBO CONTROLLED SINGLE-DOSE COMPARISON BETWEEN TWO DOSES OF INHALED FORMOTEROL VIA TURBUHALER (OXIS) AND ORAL FORMOTEROL (ATOCK TABLETS) / Data on file
SD-037-0684 / N / ON THE BRONCHODILATING EFFECT OF INHALED (R;R)- AND (S;S)- FORMOTEROL COMPARED WITH THE BRONCHODILATING EFFECT OF INHALED RAC-FORMOTEROL IN ASTHMATIC PATIENTS / Lötvall J, Palmqvist M, Ankerst J, Persson G, Rosenborg J, Bengtsson T, Rott Z, Poczi M, Devai A, Waldeck B. The effect of formoterol over 24 h in patients with asthma: The role of enantiomers.Pul Pharmacol Ther 2005; 18(2): 109-113.
SD-037-0718 / N / A COMPARISON OF EFFICACY BETWEEN FORMOTEROL TURBUHALER AND SALBUTAMOL PRESSURISED METERED DOSE INHALER AND SPACER, IN SUBJECTS WITH ACUTE SEVERE BRONCHIAL OBSTRUCTION / Boonsawat W, Charoenratanakul S, Pothirat C, Sawanyawisuth K, Seearamroongruang T, Bengtsson T, Brander R, Selroos O. Formoterol (OXIS®) Turbuhaler® as a rescue therapy compared with salbutamol pMDI plus spacer in patients with acute severe asthma.Respir Med 2003; 97(9): 1067-1074.
SD-037-0724 / N / COMPARISON OF FORMOTEROL (OXIS) VIA TURBUHALER WITH SALBUTAMOL VIA PRESSURIZED METERED DOSE INHALER AND SPACER IN PATIENTS WITH ACUTE SEVERE BRONCHOCONSTRICTION / RubinfeldAR, Scicchitano R, Hunt A, Thompson PJ, Van Nooten A, Selroos O. Formoterol Turbuhaler® as reliever medication in patients with acute asthma.Eur Respir J 2006; 27(4): 735-741.
SD-037-0738 / N / TOLERABILITY OF HIGH DOSE FORMOTEROL VS. HIGH DOSE TERBUTALINE IN ASTHMATIC CHILDREN AFTER INHALATION VIA TURBUHALER / Kaae R, Agertoft L, Pedersen S, Nordvall SL, Pedroletti C, Bengtsson T, Johannes-Hellberg I, Rosenborg J. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline. Br J Clin Pharmacol 2004; 58(4): 411-418.