Clinical trial NCT00605891: Dose Finding Study of CHF 4226 for Treating Patients With COPD
Official title: A Randomized, Controlled,14-Treatment Day, Multicenter Study to Determine the Optimal Efficacious and Safe Dose of CHF 4226 in a Metered Dose Inhaler in Treating Patients With Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
Collaborators: name: Chiesi USA, Inc.
First posted: 2008-01-31
Enrollment: 278
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to identify the optimal once-daily dose of CHF 4226 to be further developed for the treatment of patients with COPD.


Eligibility criteria: Inclusion Criteria:

* Patient has signed an IRB-/Ethics Committee-approved Informed Consent form
* Patient is a male or non-pregnant female between the ages of 40 - 75 years, inclusive
* Patient has a current or past smoking history of at least 15 pack-years
* Patient has a clinical diagnosis of COPD in accordance with the recommendations of the National Heart Lung and Blood Institute/World Health Organization (NHLBI/WHO) Global Initiative for Chronic Obstructive Lung Disease (GOLD)
* Patient meets the following requirements after an FEV1 albuterol reversibility test (i.e., 30 minutes following 200 mcg (metered dose) albuterol/salbutamol pMDI):
* FEV1 is at least 0.9L
* FEV1 of 40% - 70%, inclusive, of patient's predicted normal value
* Change in FEV1 \> 4% of patient's predicted normal value

  * If change in FEV1 \< 4% of patient's predicted normal value, then this requirement must be met after retesting during the run-in period, at least 24 hours prior to Day -1
* FEV1/FVC \< 70%

Exclusion Criteria:

* Patient has a history of asthma, allergic rhinitis, or atopy
* Patient has a blood eosinophil count \> 500/microliter
* Patient had a COPD exacerbation or a lower respiratory tract infection within 8 weeks prior to screening, or during the run-in period, that resulted in the use of an antibiotic, or oral or parenteral corticosteroids
* Patient is on an inhaled corticosteroid that has been initiated, or the effective dose has been changed, within 4 weeks prior to screening or during the run-in period
* Patient has an uncontrolled cardiovascular (e.g., uncontrolled hypertension), respiratory, hematologic, immunologic, renal, neurologic, hepatic, endocrine (e.g., uncontrolled diabetes mellitus) or other disease, or any condition that might, in the judgment of the Investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study
* Patient has a history of coronary artery disease, cerebrovascular disease, cardiac arrhythmias
* Patient has a concomitant disease of poor prognosis (e.g., cancer)
* Patient has a serum potassium value ≤ 3.5 mEq/L or \>5.5mEq/L and/or a fasting serum glucose value ≥ 140 mg/dL
* Patient has an abnormal QTc Fridericia interval value in the Screening visit ECG test (i.e., \> 450 msec in males or \> 470 msec in females)
* Patient has developed Cor Pulmonale
* Patient is receiving long term oxygen therapy, i.e., ≥ 16 hours/24-hour period, every day
* Patient has a known intolerance/hypersensitivity to Beta2-adrenergic agonists, propellant gases/excipients
* Patient is receiving treatment with a tricyclic antidepressant or a monoamine oxidase inhibitor (MAOI)
* Patient has received a live-attenuated virus vaccination within two weeks prior to screening or during the run-in
* Patient is pregnant or lactating female, or female at risk of pregnancy (i.e., not using an adequate contraceptive method)
* Patient is mentally or legally incapacitated
* Patient has participated in another investigational study within 30 days prior to screening
* Patient abuses alcohol or other substances
* Patient is potentially non-compliant or unable to perform required outcome measurements of the protocol

Primary outcomes:
measure: Change in FEV1
timeFrame: Day 1 to Day 14 (+3 days)
Secondary outcomes:
measure: FEV1
timeFrame: 10 and 30 min, 1, 2, and 3 hrs post dose on Day 1, Day 2 and Day 14 (+3)
measure: ECG/QTc
timeFrame: pre dose and post dose at 30' on Days 1, 2 and 14 (+3)
measure: Fasting serum potassium
timeFrame: pre dose and post dose at 30' on Days 1, 2 and 14 (+3)
measure: Fasting glucose
timeFrame: pre dose and post dose at 30' on Days 1, 2 and 14 (+3)
measure: Change in FEV1
timeFrame: 10 and 30 min, 1, 2, and 3 hrs post dose on Day 1, Day 2 and Day 14 (+3)
Other outcomes:
Locations:
city: Jonesboro
country: United States
facility: Clopton Clinic
state: Arkansas
city: Fresno
country: United States
facility: ABM Research Center
state: California
city: San Diego
country: United States
facility: UCSD - Clinical Trials Center
state: California
city: San Diego
country: United States
facility: Institute of Healthcare Assessment Inc.
state: California
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Clearwater
country: United States
facility: Clinical Research of West Florida
state: Florida
city: DeLand
country: United States
facility: University Clinical Research - DeLand, LLC
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Naperville
country: United States
facility: Edward Hospital and Helath Services, Center for Clinical Trials
state: Illinois
city: Anderson
country: United States
facility: Community Clinical Research Center
state: Indiana
city: Ann Arbor
country: United States
facility: ClinSite, LLC
state: Michigan
city: Canton
country: United States
facility: ClinSite
state: Michigan
city: Cherry Hill
country: United States
facility: Delaware Valley Clinical Research
state: New Jersey
city: Statesville
country: United States
facility: Carolina Pharmaceutical Research
state: North Carolina
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Sylvania
country: United States
facility: Toledo Center for Clinical Research
state: Ohio
city: Medford
country: United States
facility: Clinical Research Institute of Southern Oregon PC
state: Oregon
city: Medford
country: United States
facility: Pulmonary Consultants - Research Department
state: Oregon
city: North Charleston
country: United States
facility: Lowcountry Lung and Critical Care, PA
state: South Carolina
city: Amarillo
country: United States
facility: Amarillo Center for Clinical Research, Ltd.
state: Texas
city: Katy
country: United States
facility: Breath of Life Research Institute
state: Texas
city: Tyler
country: United States
facility: The University of Texas Health Center at Tyler
state: Texas
city: Madison
country: United States
facility: University of Wisconsin-Allergy/Asthma
state: Wisconsin
city: Beroun
country: Czech Republic
facility: Ordinace pro nemoci dychaciho ustroji
city: Kutna Hora
country: Czech Republic
facility: OTRAN
city: Kutna Hora
country: Czech Republic
facility: Plicni a alergologicka ambulance
city: Lovosice
country: Czech Republic
facility: Pneumolog, internista
city: Praha 3 - Zizkov
country: Czech Republic
facility: Plicni ambulance
city: Praha 5
country: Czech Republic
facility: Nemocnice Na Homolce Plicni ambulance
city: Rokycany
country: Czech Republic
facility: Plicni ambulance Rokycany
city: Berlin
country: Germany
facility: Medars GmbH
city: Geesthacht
country: Germany
facility: Lungenzentrum Geesthacht
city: Grosshansdorf
country: Germany
facility: Pneumologisches Forschungsinstitut GmbH
city: Hamburg
country: Germany
facility: Pneumologisches Forschungsinstitut Niederlassung Hamburg
city: Leipzig
country: Germany
facility: Robert-Koch-Klinik
city: Magdeburg
country: Germany
facility: SMO, MD GmbH
city: Ruedersdorf
country: Germany
facility: IFG GmbH
city: Gdansk
country: Poland
facility: Medcare Specjalistyczna Opieka Medyczna NZOZ
city: Gdansk
country: Poland
facility: NZOZ Non-nocere
city: Lodz
country: Poland
facility: Klinika Pulmonologii i Alergologii
city: Proszowice
country: Poland
facility: SPZOZ w Proszowicach Oddzial Chorob Pluc
city: Brasov
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Brasov
city: Bucharest
country: Romania
facility: Spitalul de Urgenta "Prof. Dr. Dimitrie Gerota"
city: Bucharest
country: Romania
facility: Spitalul Clinic de Urgenta Militar Central "Davila"
city: Bucharest
country: Romania
facility: Spitalul Clinic "Sf. Maria"
city: Bucharest
country: Romania
facility: Institutul National de Pneumoftisiologie "M. Nasta"
city: Constanta
country: Romania
facility: Spitalul de Pneumoftiziologie Constanta
city: Mowbray
country: South Africa
facility: UCT Lung Institute
state: Cape Town
city: Bellville
country: South Africa
facility: Tiervlei Trial Center, Karl Bremer Hospital
Study officials:
affiliation: National Jewish Medical & Research Center
name: Barry Make, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chiesi Farmaceutici S.p.A.
name: Steven E Linberg, Ph.D.
role: STUDY_DIRECTOR
References:
citation: Matera MG, Cazzola M. ultra-long-acting beta2-adrenoceptor agonists: an emerging therapeutic option for asthma and COPD? Drugs. 2007;67(4):503-15. doi: 10.2165/00003495-200767040-00002.
citation: Cazzola M, Matera MG, Lotvall J. Ultra long-acting beta 2-agonists in development for asthma and chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2005 Jul;14(7):775-83. doi: 10.1517/13543784.14.7.775.
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citation: Kikkawa H, Isogaya M, Nagao T, Kurose H. The role of the seventh transmembrane region in high affinity binding of a beta 2-selective agonist TA-2005. Mol Pharmacol. 1998 Jan;53(1):128-34. doi: 10.1124/mol.53.1.128.
citation: Rossoni G, Manfredi B, Razzetti R, Civelli M, Bongrani S, Berti F. Positive interaction of the beta2-agonist CHF 4226.01 with budesonide in the control of bronchoconstriction induced by acetaldehyde in the guinea-pigs. Br J Pharmacol. 2005 Feb;144(3):422-9. doi: 10.1038/sj.bjp.0706096.
citation: Rossoni G, Manfredi B, Razzetti R, Civelli M, Berti F. Positive interaction of the novel beta2-agonist carmoterol and tiotropium bromide in the control of airway changes induced by different challenges in guinea-pigs. Pulm Pharmacol Ther. 2007;20(3):250-7. doi: 10.1016/j.pupt.2006.01.004. Epub 2006 Mar 14.
citation: Voss HP, Shukrula S, Wu TS, Donnell D, Bast A. A functional beta-2 adrenoceptor-mediated chronotropic response in isolated guinea pig heart tissue: selectivity of the potent beta-2 adrenoceptor agonist TA 2005. J Pharmacol Exp Ther. 1994 Oct;271(1):386-9.
citation: Kikkawa H, Kanno K, Ikezawa K. TA-2005, a novel, long-acting, and selective beta 2-adrenoceptor agonist: characterization of its in vivo bronchodilating action in guinea pigs and cats in comparison with other beta 2-agonists. Biol Pharm Bull. 1994 Aug;17(8):1047-52. doi: 10.1248/bpb.17.1047.
citation: Voss HP, Donnell D, Bast A. Atypical molecular pharmacology of a new long-acting beta 2-adrenoceptor agonist, TA 2005. Eur J Pharmacol. 1992 Dec 1;227(4):403-9. doi: 10.1016/0922-4106(92)90158-r.
citation: Kikkawa H, Naito K, Ikezawa K. Tracheal relaxing effects and beta 2-selectivity of TA-2005, a newly developed bronchodilating agent, in isolated guinea pig tissues. Jpn J Pharmacol. 1991 Oct;57(2):175-85. doi: 10.1254/jjp.57.175.
citation: Spadari-Bartfisch RC, Santos IN, Vanderlei LC, Marcondes FK. Pharmacological evidence for beta2-adrenoceptor in right atria from stressed female rats. Can J Physiol Pharmacol. 1999 Jun;77(6):432-40.