Dose Finding Study of CHF 4226 for Treating Patients With COPD

Chronic Obstructive Pulmonary Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00605891
• Other study ID #: US/PR/033009/001/05
• Secondary ID: EudraCT Number:
• Status: Completed
• Phase: Phase 2
• First received: January 18, 2008
• Last updated: April 7, 2017
• Start date: October 2006
• Est. completion date: June 2007

Study information

• Verified date: April 2017
• Source: Chiesi Farmaceutici S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 278
• Est. completion date: June 2007
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• carmoterol (CHF 4226)
carmoterol pMDI 2.0 µg once a day, in the morning (1 puff of carmoterol 1.0 mcg + 1 puff of carmoterol 1.0 mcg)
• carmoterol (CHF 4226)
carmoterol pMDI 1.0 µg once a day, in the morning (1 puff of carmoterol 1.0 mcg + 1 puff of placebo pMDI))
• carmoterol (CHF 4226)
carmoterol pMDI 4.0 µg once a day, in the morning (1 puff of carmoterol 2.0 mcg + 1 puff of carmoterol 2.0 mcg)
• salmeterol
Salmeterol 50 µg DPI, in the morning and in the evening (1 blister BID)
• placebo
Placebo pMDI once a day, in the morning (1 puff of placebo pMDI + 1 puff of placebo pMDI)

Locations

Country	Name	City	State
Czech Republic	Ordinace pro nemoci dychaciho ustroji	Beroun
Czech Republic	OTRAN	Kutna Hora
Czech Republic	Plicni a alergologicka ambulance	Kutna Hora
Czech Republic	Pneumolog, internista	Lovosice
Czech Republic	Plicni ambulance	Praha 3 - Zizkov
Czech Republic	Nemocnice Na Homolce Plicni ambulance	Praha 5
Czech Republic	Plicni ambulance Rokycany	Rokycany
Germany	Medars GmbH	Berlin
Germany	Lungenzentrum Geesthacht	Geesthacht
Germany	Pneumologisches Forschungsinstitut GmbH	Grosshansdorf
Germany	Pneumologisches Forschungsinstitut Niederlassung Hamburg	Hamburg
Germany	Robert-Koch-Klinik	Leipzig
Germany	SMO, MD GmbH	Magdeburg
Germany	IFG GmbH	Ruedersdorf
Poland	Medcare Specjalistyczna Opieka Medyczna NZOZ	Gdansk
Poland	NZOZ Non-nocere	Gdansk
Poland	Klinika Pulmonologii i Alergologii	Lodz
Poland	SPZOZ w Proszowicach Oddzial Chorob Pluc	Proszowice
Romania	Spitalul Clinic Judetean de Urgenta Brasov	Brasov
Romania	Institutul National de Pneumoftisiologie "M. Nasta"	Bucharest
Romania	Spitalul Clinic "Sf. Maria"	Bucharest
Romania	Spitalul Clinic de Urgenta Militar Central "Davila"	Bucharest
Romania	Spitalul de Urgenta "Prof. Dr. Dimitrie Gerota"	Bucharest
Romania	Spitalul de Pneumoftiziologie Constanta	Constanta
South Africa	Tiervlei Trial Center, Karl Bremer Hospital	Bellville
South Africa	UCT Lung Institute	Mowbray	Cape Town
United States	Amarillo Center for Clinical Research, Ltd.	Amarillo	Texas
United States	Community Clinical Research Center	Anderson	Indiana
United States	ClinSite, LLC	Ann Arbor	Michigan
United States	ClinSite	Canton	Michigan
United States	Delaware Valley Clinical Research	Cherry Hill	New Jersey
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	Clinical Research of West Florida	Clearwater	Florida
United States	University Clinical Research - DeLand, LLC	DeLand	Florida
United States	National Jewish Medical and Research Center	Denver	Colorado
United States	ABM Research Center	Fresno	California
United States	Clopton Clinic	Jonesboro	Arkansas
United States	Breath of Life Research Institute	Katy	Texas
United States	University of Wisconsin-Allergy/Asthma	Madison	Wisconsin
United States	Clinical Research Institute of Southern Oregon PC	Medford	Oregon
United States	Pulmonary Consultants - Research Department	Medford	Oregon
United States	Edward Hospital and Helath Services, Center for Clinical Trials	Naperville	Illinois
United States	Lowcountry Lung and Critical Care, PA	North Charleston	South Carolina
United States	Institute of Healthcare Assessment Inc.	San Diego	California
United States	UCSD - Clinical Trials Center	San Diego	California
United States	Carolina Pharmaceutical Research	Statesville	North Carolina
United States	Toledo Center for Clinical Research	Sylvania	Ohio
United States	Clinical Research of West Florida, Inc.	Tampa	Florida
United States	The University of Texas Health Center at Tyler	Tyler	Texas
United States	Palm Beach Research Center	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Chiesi Farmaceutici S.p.A.	Chiesi USA

Countries where clinical trial is conducted

United States,  Czech Republic,  Germany,  Poland,  Romania,  South Africa, 

References & Publications (11)

Cazzola M, Matera MG, Lötvall 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. Review. — View 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. — View 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. — View 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. — View 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. Review. — View Citation

Matsukawa M, Takeda K, Shima H, Tagawa K, Banno K, Sato T. Enzyme-linked immunosorbent assay for TA-2005-glucuronide in human plasma. J Pharm Biomed Anal. 1998 Jun;17(2):245-54. — View 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. Epub 2006 Mar 14. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in FEV1		Day 1 to Day 14 (+3 days)
Secondary	FEV1		10 and 30 min, 1, 2, and 3 hrs post dose on Day 1, Day 2 and Day 14 (+3)
Secondary	ECG/QTc		pre dose and post dose at 30' on Days 1, 2 and 14 (+3)
Secondary	Fasting serum potassium		pre dose and post dose at 30' on Days 1, 2 and 14 (+3)
Secondary	Fasting glucose		pre dose and post dose at 30' on Days 1, 2 and 14 (+3)
Secondary	Change in FEV1		10 and 30 min, 1, 2, and 3 hrs post dose on Day 1, Day 2 and Day 14 (+3)

External Links

•   Study Record on EU Clinical Trials Register including results