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A 6-week Dose Ranging Study of CHF 5259 pMDI in Subjects With Chronic Obstructive Pulmonary Disease (GLIMMER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03084796
Recruitment Status : Completed
First Posted : March 21, 2017
Last Update Posted : May 21, 2019
Information provided by (Responsible Party):
Chiesi Farmaceutici S.p.A.

Brief Summary:
The purpose of this study is to evaluate the dose-response of different doses of CHF 5259 pMDI on lung function and other clinical outcomes, to identify the optimal dose(s) in terms of benefit/ risk ratio for further development in the target subject population.

Condition or disease Intervention/treatment Phase
COPD Drug: CHF 5259 Drug: Placebo Drug: Tiotropium Bromide 18 MCG Inhalation Capsule Phase 2

Detailed Description:

This is a phase II, multicenter, randomized, double-blind, placebo and active controlled dose-ranging 6-arm parallel group study to identify the optimal dose of CHF 5259 pMDI with respect to lung function and other clinical efficacy and safety outcomes.

After a 2 week run-in period under rescue albuterol and background ICS as needed, patients will be randomized to one of the 6 study treatment groups. Following randomization, subjects will be assessed after 3 weeks and 6 weeks of study treatment at the center. A follow-up phone call will be performed a week after the last visit.

During the study, daily symptoms, rescue and background medication use and compliance with the study drug will be recorded via a subject diary. Treatment-Emergent Adverse Events (TEAEs) will be assessed and recorded throughout the study. At screening and subsequent visits, subjects will undergo physical and vital signs examinations, spirometry measurements, and 12-lead ECG. Symptoms and COPD health status will be assessed through validated questionnaires. Routine hematology, blood chemistry, and pregnancy testing will be performed before enrollment and at end of study. 24-hour digital recording of ECGs (Holter) will be performed before and after the first dose and just before the last dose of study treatment.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 735 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: A 6-week, Multicenter, Randomized, Double-blind, Placebo and Active-controlled, Parallel Group, Dose-ranging Study to Evaluate the Efficacy and Safety of 4 Doses of CHF 5259 pMDI (HFA Glycopyrronium Bromide Via Pressurized Metered Dose Inhaler) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Actual Study Start Date : July 28, 2017
Actual Primary Completion Date : May 23, 2018
Actual Study Completion Date : June 6, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Diseases

Arm Intervention/treatment
Experimental: Treatment A
CHF 5259 pMDI Dose 1
Drug: CHF 5259
Dose Response: Test one of four different doses of CHF 5259

Experimental: Treatment B
CHF 5259 pMDI Dose 2
Drug: CHF 5259
Dose Response: Test one of four different doses of CHF 5259

Experimental: Treatment C
CHF 5259 pMDI Dose 3
Drug: CHF 5259
Dose Response: Test one of four different doses of CHF 5259

Experimental: Treatment D
CHF 5259 pMDI Dose 4
Drug: CHF 5259
Dose Response: Test one of four different doses of CHF 5259

Placebo Comparator: Treatment E
Placebo Control
Drug: Placebo
Placebo Control

Active Comparator: Treatment F
Tiotropium Bromide inhalation powder, 18 µg
Drug: Tiotropium Bromide 18 MCG Inhalation Capsule
Active Control

Primary Outcome Measures :
  1. Change from baseline in FEV1 AUC(0-12h) normalized by time at Week 6. [ Time Frame: 6 Weeks ]

Secondary Outcome Measures :
  1. Change from baseline in FEV1 AUC0-12h normalized by time at Day 1 [ Time Frame: 6 Weeks ]
  2. Change from baseline in FEV1 AUC0-4h normalized by time at Day 1 and Week 6 [ Time Frame: 6 Weeks ]
  3. Change from baseline in pre-dose morning FEV1 at Week 3 and Week 6 [ Time Frame: 3 Weeks & 6 Weeks ]
  4. Time to onset of action (change from baseline in post-dose FEV1 ≥ 100 mL) at Day 1 [ Time Frame: 6 Weeks ]
  5. TDI focal score at Week 3 and Week 6 [ Time Frame: 6 Weeks ]
  6. Change from baseline in %rescue medication-free days [ Time Frame: 6 Weeks ]
  7. Change from baseline in average COPD symptom scores [ Time Frame: 6 Weeks ]
  8. Adverse Events (AEs) and Adverse Drug Reactions (ADRs) [ Time Frame: 6 Weeks ]
  9. Vital signs (systolic and diastolic blood pressure) [ Time Frame: 6 Weeks ]
  10. 24-hour digital Holter ECG parameters (HR, QTcF, QRS, PR) [ Time Frame: 6 Weeks ]
  11. 24-hour HR average, minimum and maximum [ Time Frame: 6 Weeks ]
  12. 24-hour digital Holter ECG abnormal findings [ Time Frame: 6 Weeks ]
  13. Standard blood chemistry and hematology [ Time Frame: 6 Weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male or female subjects aged ≥ 40 who have signed an Informed Consent Form prior to initiation of any study-related procedure.
  • Subjects with a diagnosis of COPD (according to GOLD 2017 Global Strategy for the Diagnosis, Management and Prevention of COPD Report) at least 12 months before the screening visit.
  • Current smokers or ex-smokers who quit smoking at least 6 months prior to screening visit, with a smoking history of at least 10 pack years
  • A post-bronchodilator FEV1 ≥50% and <80% of the predicted normal value and,
  • a post-bronchodilator FEV1/FVC < 0.7 at screening and
  • a demonstrated reversibility to ipratropium defined as ΔFEV1 ≥ 5% over baseline 30-45 minutes after inhaling 4 puffs of ipratropium
  • Subjects under regular COPD therapy for at least 2 months prior to screening with either inhaled LAMA, inhaled ICS/LABA, inhaled ICS + LAMA
  • Symptomatic subjects at screening with a CAT score ≥10. This criterion must be confirmed at randomization
  • Symptomatic subjects with a BDI focal score ≤ 10. This criterion must be confirmed at randomization
  • A cooperative attitude and ability to demonstrate correct use of the inhalers and e-diary.

Exclusion Criteria:

  • Pregnant or lactating women and all women physiologically capable of becoming pregnant UNLESS they are willing to use highly effective birth control methods
  • Diagnosis of asthma or Asthma-COPD Overlap Syndrome (ACOS) as described in GINA Report 2016, history of allergic rhinitis or atopy (atopy which may raise contra-indications or impact the efficacy of the study treatment according to Investigator's judgment)
  • COPD Exacerbations: a moderate or severe COPD exacerbation that has not resolved ≤14 days prior to screening and ≤30 days following the last dose of any oral/systemic corticosteroid or antibiotic (whichever comes last). A Moderate or Severe COPD exacerbation during the run-in period
  • Use of antibiotics for a lower respiratory tract infection in the 4 weeks prior to screening or during run-in
  • Subjects treated with non-cardio-selective β-blockers in the month preceding screening or during the run-in period
  • Subjects treated with long-acting anti-histamines unless taken at stable regimen at least 2 months prior to screening and to be maintained constant during the study, or if taken as needed
  • Subjects requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia
  • Known respiratory disorders other than COPD which may impact the efficacy of the study treatment according the Investigator's judgment.
  • Subjects who have clinically significant cardiovascular condition
  • Subjects who have a clinically significant abnormal 12-lead ECG that results in active medical problem which may impact the safety of the subject according to Investigator's judgement
  • Subjects whose 12-lead ECG shows Fridericia corrected QT interval (QTcF) >450 ms for males or QTcF >470 ms for females at screening visit
  • Medical diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction that in the opinion of the Investigator would prevent use of anticholinergic agents
  • History of hypersensitivity to M3 receptor antagonists, β2-adrenergic receptor agonist, corticosteroids or any of the excipients contained in any of the formulations used in the study which may raise contra-indications or impact the efficacy of the study treatment according to the Investigator's judgement
  • Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study treatment according to Investigator's judgement
  • Subjects with serum potassium levels <3.5 mEq/L (or 3.5 mmol/L) at screening
  • Use of potent cytochrome P450 2D6 and 3A4 inhibitors within 4 weeks prior to screening
  • Unstable or uncontrolled concurrent disease; fever, endocrine disease, gastrointestinal disease; neurological disease; hematological disease; autoimmune disorders, or other which may impact the feasibility of the results of the study according to Investigator's judgment
  • History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening
  • Subjects who have received an investigational drug within 1 month or 5 half-lives (whichever is greater) prior to screening visit, or have been previously randomized in this trial, or are currently participating in another clinical trial.
  • Subjects who are mentally or legally incapacitated, or subjects accommodated in an establishment as a result of an official or judicial order.
  • Subjects who have undergone major surgery in the 3 months prior to screening visit or have a planned surgery during the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03084796

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Sponsors and Collaborators
Chiesi Farmaceutici S.p.A.
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Principal Investigator: Edward Kerwin, MD Crisor LLC c/o Clinical Research Institute of Southern Oregon, Inc.
Additional Information:
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, Burney P, Carapetis J, Chen H, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin V, Flaxman AD, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez-Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, Johns N, Karthikeyan G, Kassebaum N, Keren A, Khoo JP, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGrath J, Mensah GA, Merriman TR, Michaud C, Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Moran A, Mulholland K, Nair MN, Naldi L, Narayan KM, Nasseri K, Norman P, O'Donnell M, Omer SB, Ortblad K, Osborne R, Ozgediz D, Pahari B, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce K, Pope CA 3rd, Porrini E, Pourmalek F, Raju M, Ranganathan D, Rehm JT, Rein DB, Remuzzi G, Rivara FP, Roberts T, De León FR, Rosenfeld LC, Rushton L, Sacco RL, Salomon JA, Sampson U, Sanman E, Schwebel DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T, Undurraga EA, Venketasubramanian N, Vijayakumar L, Vos T, Wagner GR, Wang M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson JD, Woolf AD, Wulf S, Yeh PH, Yip P, Zabetian A, Zheng ZJ, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15;380(9859):2095-128. doi: 10.1016/S0140-6736(12)61728-0. Erratum in: Lancet. 2013 Feb 23;381(9867):628. AlMazroa, Mohammad A [added]; Memish, Ziad A [added].
Chiesi Farmaceutici S.p.A. Randomised, double-blind, placebo-controlled, cross-over study to investigate the bronchodilator efficacy and safety after single and repeated administrations of different doses of glycopyrrolate via pMDI in moderate to severe COPD patients (GLYCO2). 2012 Jul 19; CCD-0916-CSR-0054.
Novartis Pharmaceuticals Corporation. SEEBRI™ NEOHALER® US Prescribing Information. East Hanover, New Jersey; 2016 Jan.
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Chiesi Farmaceutici S.p.A. A multinational, multicentre, randomised, double-blind, placebo-controlled, 2-way crossover study to evaluate the efficacy and safety of glycopyrrolate bromide administered via pMDI (CHF 5259), for the treatment of patients with chronic obstructive pulmonary disease. 2015 Nov 05; CCD-05993AA1-09.
Chiesi Farmaceutici S.p.A. A multicentre, randomised, double-blind, active-controlled, 4-way cross-over study to evaluate the efficacy and safety of a free combination of 3 doses of glycopyrrolate with fixed combination beclomethasone dipropionate plus formoterol (FOSTER®) in a metered dose inhaler for the treatment of patients with chronic obstructive pulmonary disease (COPD). 2013 May 16; CCD-1106-PR-0066.
Chiesi Farmaceutici S.p.A. Randomized, double-blind, active controlled, 3-arm parallel group, multi-national, multi-centre study to evaluate the cardiac safety of two doses of glycopyrrolate bromide (25µg and 50µg BID) delivered via HFA pMDI both combined with FOSTER® 100/6µg BID delivered via HFA pMDI versus FOSTER® 100/6µg BID delivered via HFA pMDI in patients with moderate to severe COPD. 2012 Jan 10; CCD-1107-PR-0067.
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Responsible Party: Chiesi Farmaceutici S.p.A. Identifier: NCT03084796    
Other Study ID Numbers: CCD-05993AA3-02
First Posted: March 21, 2017    Key Record Dates
Last Update Posted: May 21, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Lung Diseases
Respiratory Tract Diseases
Tiotropium Bromide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action