Dose Finding Study of CHF 4226 for Treating Patients With COPD

Study Identifier:
US/PR/033009/001/05
ClinicalTrials.gov Identifier:
NCT00605891
EudraCT Identifier:
N/A
EU CT ID:
N/A
Study Contact Information:
N/A
See Study Publication Below
Study Complete

Study Details

Medical Condition
  • Chronic Obstructive Pulmonary Disease
Study Drug
  • Drug: carmoterol (CHF 4226)
  • Drug: salmeterol
  • Drug: placebo
Date
Oct 2006 - Jun 2007
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 40 - 75 Years
Requirements Information
Inclusion and Exclusion 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
Healthy Volunteers
No

Protocol 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.

Study Locations

Location
Status
Location
Clopton Clinic
Jonesboro, Arkansas, United States, 72401
Status
N/A
Location
ABM Research Center
Fresno, California, United States, 93720
Status
N/A
Location
UCSD - Clinical Trials Center
San Diego, California, United States, 92103
Status
N/A
Location
Institute of Healthcare Assessment Inc.
San Diego, California, United States, 92120
Status
N/A
Location
National Jewish Medical and Research Center
Denver, Colorado, United States, 80206
Status
N/A
Location
Clinical Research of West Florida
Clearwater, Florida, United States, 33765
Status
N/A
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Study Publications

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.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.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. doi: 10.1016/s0731-7085(97)00186-6.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.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.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.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.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.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.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.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.