Confirmatory Dose Finding Study of 2 Dosages of CHF 4226 pMDI (Carmoterol) in Patients With COPD

Study Identifier:
CCD-0706-PR-0026
ClinicalTrials.gov Identifier:
NCT00640484
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: placebo
  • Drug: salmeterol
Date
Apr 2008 - Oct 2008
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
  • Signed IRB approved Informed Consent form
  • Male or non-pregnant female, 40 -75 years old, inclusive
  • Current or past cigarette smoking history of at least 15 pack-years
  • Clinical diagnosis of COPD in accordance with recommendations of the National Heart Lung and Blood Institute/World Health Organization (NHLBI/WHO) Global Initiative for Chronic Obstructive Lung Disease (GOLD)
  • Patient meets following requirements after FEV1 albuterol reversibility test (i.e., 30 minutes after 200μg (metered dose) albuterol MDI):
  • FEV1/FVC \< 70%
  • FEV1 is at least 0.9L
  • FEV1 30% - 80%, inclusive, of patient's predicted normal value; ∆FEV1 \> 5% of pre-albuterol value
  • If ∆FEV1 \< 5% of pre-albuterol value, requirement must be met after retesting during run-in period, at least 24 hours prior to Period 1/Visit 1.
Exclusion Criteria
  • History of asthma
  • Blood eosinophil count \> 500/microliters
  • History of allergic rhinitis or atopy
  • COPD exacerbation or lower respiratory tract infection within 8 weeks prior to screening, or during run-in period, that resulted in use of an antibiotic, or oral or parenteral corticosteroids
  • Inhaled corticosteroid that has been initiated, or effective dose has been changed, within 4 weeks prior to screening or during run-in period
  • 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 Investigator's judgment, place patient at undue risk or potentially compromise study results or interpretation
  • History of coronary artery disease, cerebrovascular disease, cardiac arrhythmias
  • Lung cancer or history of lung cancer
  • Active cancer or history of cancer with \< 5 years disease free survival time (with or without evidence of local recurrence or metastases). Localized basal cell carcinoma (without metastases) of skin is acceptable.
  • Serum potassium value ≤ 3.5 mEq/L or \> 5.5mEq/L and/or fasting serum glucose value ≥ 140 mg/dL
  • Abnormal QTcF interval value in Screening visit ECG test (i.e., \> 450 msec in males or \> 470 msec in females)
  • Cor Pulmonale
  • Long term oxygen therapy, i.e., \> 16 hours/24-hour period, every day, unless patient resides at elevation \> 4000ft
  • Use of any of the following medications prior to Screening, without meeting specified minimum washout period:
  • Long acting anti-cholinergic agent (i.e., tiotropium): 7 days
  • Short acting anti-cholinergics: 8 hours
  • Fixed combinations of β2-agonists and inhaled corticosteroids: 48 hours
  • Fixed combinations of an anti-cholinergic and short acting β2-agonist: 8 hours
  • Long-acting β2-agonists: 48 hours
  • Short acting β2-agonists (other than those prescribed in the study): 6 hours
  • Theophylline and other xanthines: 1 week
  • Parenteral or oral corticosteroids: 1 month
  • Patient has taken any non-permitted medication
  • Patient has received live-attenuated virus vaccination within two weeks prior to screening or during run-in (inactivated Influenza vaccination is acceptable if given \> 48 hours prior to Screening)
  • Known intolerance/hypersensitivity to β2-adrenergic agonists, propellant gases/excipients
  • Patient is pregnant or lactating female, or female at risk of pregnancy (i.e., not using adequate contraceptive method: surgical sterilization \[e.g., bilateral tubal ligation\], hormonal contraception \[implantable, patch, oral\], IUD, and double-barrier methods \[any double combination of: male or female condom with spermicidal gel, diaphragm, sponge, cervical cap\]).
  • Patient is mentally or legally incapacitated
  • Patient has participated in another investigational study within 30 days prior to screening
  • Abuse of alcohol or other substances
  • Patient does not maintain regular day/night, waking/sleeping cycles (e.g., night shift worker)
  • Patient is potentially non-compliant or unable to perform required protocol outcome measurements
Healthy Volunteers
No

Protocol Summary

The purpose of this study is to confirm the dose of CHF 4226 (carmoterol) that should be given once a day to patients with COPD in order for the effect to last for 24 hours.

Study Locations

Location
Status
Location
Horizon Clinical Research Associates, PLLC
Gilbert, Arizona, United States, 85295
Status
N/A
Location
Pulmonary Associates, PA
Phoenix, Arizona, United States, 85006
Status
N/A
Location
UCLA David Geffen School of Medicine
Los Angeles, California, United States, 90095
Status
N/A
Location
University Clinical Research - DeLand, LLC
DeLand, Florida, United States, 32720
Status
N/A
Location
Pulmonary Medicine and Critical Care
Austell, Georgia, United States, 30106
Status
N/A
Location
Sneeze, Wheeze & Itch Associates, LLC
Normal, Illinois, United States, 61761
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.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.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.