Tags

Type your tag names separated by a space and hit enter

Dose-response to inhaled glycopyrrolate delivered with a novel Co-Suspension™ Delivery Technology metered dose inhaler (MDI) in patients with moderate-to-severe COPD.
Respir Res. 2016 09 02; 17(1):109.RR

Abstract

BACKGROUND

This study forms part of the first complete characterization of the dose-response curve for glycopyrrolate (GP) delivered using Co-Suspension™ Delivery Technology via a metered dose inhaler (MDI). We examined the lower GP MDI dose range to determine an optimal dose for patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).

METHODS

This randomized, double-blind, chronic-dosing, balanced incomplete-block, placebo-controlled, crossover study compared six doses of GP MDI (18, 9, 4.6, 2.4, 1.2, and 0.6 μg, twice daily [BID]) with placebo MDI BID and open-label tiotropium dry powder inhaler (18 μg, once daily [QD]) in patients with moderate-to-severe COPD. Patients were randomized into 1 of 120 treatment sequences. Each sequence included 4 of 8 treatments administered for 14-day periods separated by 7- to 21-day washout periods. The primary efficacy endpoint was change from baseline in forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV1 AUC0-12) on Day 14. Secondary efficacy endpoints included peak change from baseline (post-dose) in FEV1 and inspiratory capacity (IC) on Days 1, 7, and 14; change from baseline in morning pre-dose trough FEV1 on Days 7 and 14; change from baseline in 12-h post-dose trough FEV1 on Day 14; time to onset of action (≥10 % improvement in mean FEV1) and the proportion of patients achieving ≥12 % improvement in FEV1 on Day 1; and pre-dose trough IC on Days 7 and 14. Safety and tolerability were also assessed.

RESULTS

GP MDI 18, 9, 4.6, and 2.4 μg demonstrated statistically significant and clinically relevant increases in FEV1 AUC0-12 compared with placebo MDI following 14 days of treatment (modified intent-to-treat population = 120). GP MDI 18 μg was non-inferior to open-label tiotropium for peak change in FEV1 on Day 1 and morning pre-dose trough FEV1 on Day 14. All doses of GP MDI were well tolerated with no unexpected safety findings.

CONCLUSIONS

These efficacy and safety results support GP MDI 18 μg BID as the most appropriate dose for evaluation in Phase III trials in patients with moderate-to-severe COPD.

TRIAL REGISTRATION

ClinicalTrials.gov NCT01566773 . Registered 27 March 2012.

Authors+Show Affiliations

Department of Medicine, University of Modena and Reggio Emilia, NOCSAE, AUSL di Modena, Via Giardini 1355, 41126, Modena, MO, Italy. leonardo.fabbri@unimore.it.Clinical Research Institute of Southern Oregon, Medford, OR, USA.American Health Research, Charlotte, NC, USA.Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA.Servei de Pneumologia, Institut Clinic Respiratori, Hospital Clínic, Barcelona, Spain; University of Barcelona, Barcelona, Spain.California Research Medical Group, Fullerton, CA, USA.University at Buffalo, State University of New York, Buffalo, NY, USA.Pearl Therapeutics Inc., Morristown, NJ, USA.Pearl Therapeutics Inc., Morristown, NJ, USA.Pearl Therapeutics Inc., Morristown, NJ, USA.Pearl Therapeutics Inc., Durham, NC, USA.Pearl Therapeutics Inc., Durham, NC, USA.Pearl Therapeutics Inc., Redwood City, CA, USA.Pearl Therapeutics Inc., Morristown, NJ, USA.

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27586537

Citation

Fabbri, Leonardo M., et al. "Dose-response to Inhaled Glycopyrrolate Delivered With a Novel Co-Suspension™ Delivery Technology Metered Dose Inhaler (MDI) in Patients With Moderate-to-severe COPD." Respiratory Research, vol. 17, no. 1, 2016, p. 109.
Fabbri LM, Kerwin EM, Spangenthal S, et al. Dose-response to inhaled glycopyrrolate delivered with a novel Co-Suspension™ Delivery Technology metered dose inhaler (MDI) in patients with moderate-to-severe COPD. Respir Res. 2016;17(1):109.
Fabbri, L. M., Kerwin, E. M., Spangenthal, S., Ferguson, G. T., Rodriguez-Roisin, R., Pearle, J., Sethi, S., Orevillo, C., Darken, P., St Rose, E., Fischer, T., Golden, M., Dwivedi, S., & Reisner, C. (2016). Dose-response to inhaled glycopyrrolate delivered with a novel Co-Suspension™ Delivery Technology metered dose inhaler (MDI) in patients with moderate-to-severe COPD. Respiratory Research, 17(1), 109. https://doi.org/10.1186/s12931-016-0426-4
Fabbri LM, et al. Dose-response to Inhaled Glycopyrrolate Delivered With a Novel Co-Suspension™ Delivery Technology Metered Dose Inhaler (MDI) in Patients With Moderate-to-severe COPD. Respir Res. 2016 09 2;17(1):109. PubMed PMID: 27586537.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dose-response to inhaled glycopyrrolate delivered with a novel Co-Suspension™ Delivery Technology metered dose inhaler (MDI) in patients with moderate-to-severe COPD. AU - Fabbri,Leonardo M, AU - Kerwin,Edward M, AU - Spangenthal,Selwyn, AU - Ferguson,Gary T, AU - Rodriguez-Roisin,Roberto, AU - Pearle,James, AU - Sethi,Sanjay, AU - Orevillo,Chad, AU - Darken,Patrick, AU - St Rose,Earl, AU - Fischer,Tracy, AU - Golden,Michael, AU - Dwivedi,Sarvajna, AU - Reisner,Colin, Y1 - 2016/09/02/ PY - 2016/07/27/received PY - 2016/08/23/accepted PY - 2016/9/3/entrez PY - 2016/9/3/pubmed PY - 2017/12/5/medline KW - Bronchodilators KW - COPD maintenance KW - Co-Suspension™ Delivery Technology KW - LAMA KW - Metered dose inhaler SP - 109 EP - 109 JF - Respiratory research JO - Respir. Res. VL - 17 IS - 1 N2 - BACKGROUND: This study forms part of the first complete characterization of the dose-response curve for glycopyrrolate (GP) delivered using Co-Suspension™ Delivery Technology via a metered dose inhaler (MDI). We examined the lower GP MDI dose range to determine an optimal dose for patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). METHODS: This randomized, double-blind, chronic-dosing, balanced incomplete-block, placebo-controlled, crossover study compared six doses of GP MDI (18, 9, 4.6, 2.4, 1.2, and 0.6 μg, twice daily [BID]) with placebo MDI BID and open-label tiotropium dry powder inhaler (18 μg, once daily [QD]) in patients with moderate-to-severe COPD. Patients were randomized into 1 of 120 treatment sequences. Each sequence included 4 of 8 treatments administered for 14-day periods separated by 7- to 21-day washout periods. The primary efficacy endpoint was change from baseline in forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV1 AUC0-12) on Day 14. Secondary efficacy endpoints included peak change from baseline (post-dose) in FEV1 and inspiratory capacity (IC) on Days 1, 7, and 14; change from baseline in morning pre-dose trough FEV1 on Days 7 and 14; change from baseline in 12-h post-dose trough FEV1 on Day 14; time to onset of action (≥10 % improvement in mean FEV1) and the proportion of patients achieving ≥12 % improvement in FEV1 on Day 1; and pre-dose trough IC on Days 7 and 14. Safety and tolerability were also assessed. RESULTS: GP MDI 18, 9, 4.6, and 2.4 μg demonstrated statistically significant and clinically relevant increases in FEV1 AUC0-12 compared with placebo MDI following 14 days of treatment (modified intent-to-treat population = 120). GP MDI 18 μg was non-inferior to open-label tiotropium for peak change in FEV1 on Day 1 and morning pre-dose trough FEV1 on Day 14. All doses of GP MDI were well tolerated with no unexpected safety findings. CONCLUSIONS: These efficacy and safety results support GP MDI 18 μg BID as the most appropriate dose for evaluation in Phase III trials in patients with moderate-to-severe COPD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01566773 . Registered 27 March 2012. SN - 1465-993X UR - https://www.unboundmedicine.com/medline/citation/27586537/Dose_response_to_inhaled_glycopyrrolate_delivered_with_a_novel_Co_Suspension™_Delivery_Technology_metered_dose_inhaler__MDI__in_patients_with_moderate_to_severe_COPD_ L2 - https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-016-0426-4 DB - PRIME DP - Unbound Medicine ER -