Pneumologie 2018; 72(S 01): S83
DOI: 10.1055/s-0037-1619340
Sektion 7 – Klinische Pneumologie
Posterbegehung – Titel: COPD I
Georg Thieme Verlag KG Stuttgart · New York

Long-Term Safety of Tiotropium/Olodaterol Respimat in Patients with Moderate-to-Very Severe COPD and Renal Impairment in the TONADO Studies

S Stieglitz
1   Pneumologie, Allergologie, Schlaf- und Intensivmedizin, Petrus-Krankenhaus Wuppertal
,
C LaForce
2   Nc Clinical Research, Raleigh, USA
,
E Derom
3   Ghent University Hospital, Belgium
,
U Bothner
4   Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein
,
L Loaiza
4   Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein
,
M Trampisch
4   Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein
,
R Buhl
5   Johannes Gutenberg University Mainz
› Author Affiliations
Further Information

Publication History

Publication Date:
21 February 2018 (online)

Also available at
 

Rationale:

Lung function, symptom benefits, and safety of combined tiotropium (T) and olodaterol (O) in the treatment of COPD were established in TONADO studies (NCT01431274; NCT01431287). As T is predominantly excreted by the kidneys, we investigated the long-term safety profile of T/O in patients with renal impairment (RI) in the TONADO studies.

Methods:

Two replicate, randomized, double-blind, parallel-group, 52-week, Phase III trials assessed T/O 2.5/5 µg and 5/5 µg compared to the monocomponents T 2.5 and 5 µg, and O 5 µg (all via Respimat®) in patients with moderate to very severe COPD. Patients with mild (creatinine clearance [CLcr] 60 – 89 mL/min), moderate (CLcr 30 – 59 mL/min), or severe RI (CLcr 15 – 29 mL/min) were included. In a pre-specified safety analysis, investigator-reported treatment-emergent adverse events (AEs) were pooled from both studies. Results for the marketed doses (T/O 5/5 µg, T 5 µg, and O 5 µg) are presented.

Results:

Of 3031 patients included, 1333 (44.0%) had mild (T/O, n = 450; T, n = 434; O, n = 449), 404 (13.3%) had moderate (T/O, n = 138; T, n = 132; O, n = 134), and five (0.2%) had severe RI (T/O, n = 3; T, n = 0; O, n = 2). 46.7% of patients with RI had pre-existing cardiac disease, 45.6% had hypertension, and 13.3% had glucose metabolism disorders, including diabetes. In patients with no, mild, and moderate RI, AEs occurred in 72%, 71%, and 75% of patients, 73%, 74%, and 76% of patients, and 80%, 80%, and 84% of patients in the T/O, T, and O groups, respectively. The majority of AEs were respiratory. RI did not affect the incidence rate of any AE and there was no difference in AE incidence in patients treated with T/O versus T or O alone. In particular, there was no difference in the incidence of major adverse cardiac events, renal and urinary tract AEs, or potential anticholinergic effects (Figure).

Zoom Image
Fig. 1: *Treatment exposure time adjusted.
CI, confidence interval; MACE, major adverse cardiac event; n/a, not applicable; Olo, olodaterol;
RI, renal impairment; Tio, tiotropium.

Conclusions:

Over half the patients had RI, which was associated with higher pre-existing cardiovascular and general co-morbidity. There was no increase in AE incidence with T/O versus T or O, and the presence of RI did not affect AE incidence in any of the treatment groups. There was a low incidence of potential anticholinergic effects and no increase in potential anticholinergic effects with T/O versus O. T/O was safe and well tolerated in patients with RI.

Sponsored by Boehringer Ingelheim

Previously presented at ATS 2017