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

NCT00640484 | Completed Phase 2

• 1 other identifier: CCD-0706-PR-0026
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 15

Brief 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.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• FEV1 AUC0-24 standardized by time

  on Day 15 (after 14 days of dosing)

Secondary Outcomes (4)

• FEV1(L)

  30 min, 1, 2 ,3, 4, 6, 10, 12, 14, 16, 22, 23, and 24 hrs post dose at Visit 2 at all treatment periods

• blood pressure

  at the beginning and end of each of the four 14-day treatment periods

• heart rate

  at the beginning and end of each of the four 14-day treatment periods

• FEV1 percent change

  30 min, 1, 2 ,3, 4, 6, 10, 12, 14, 16, 22, 23, and 24 hrs post dose at Visit 2 at all treatment periods

Study Arms (4)

A

EXPERIMENTAL

CHF 4226 (carmoterol) 2 μg once a day, in the morning

Drug: carmoterol (CHF 4226)

B

EXPERIMENTAL

CHF 4226 (carmoterol) 4 μg once a day, in the morning

Drug: carmoterol (CHF 4226)

C

PLACEBO COMPARATOR

placebo once a day, in the morning

Drug: placebo

D

ACTIVE COMPARATOR

salmeterol 50 μg twice daily, in the morning and in the evening

Drug: salmeterol

Interventions

carmoterol (CHF 4226) DRUG

carmoterol (CHF 4226) 2 μg once a day, in the morning (1 puff of carmoterol 2 μg + 1 puff of placebo pMDI)

Also known as: CHF 4226, TA2005

A

placebo DRUG

placebo once a day, in the morning (1 puff of placebo pMDI + 1 puff of placebo pMDI)

C

salmeterol DRUG

Salmeterol 50 μg twice daily, in the morning and in the evening (1 blister of Serevent Diskus BID)

Also known as: Serevent Diskus/Accuhaler

D

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (15)

Horizon Clinical Research Associates, PLLC

Gilbert, Arizona, 85295, United States

Location

Pulmonary Associates, PA

Phoenix, Arizona, 85006, United States

Location

UCLA David Geffen School of Medicine

Los Angeles, California, 90095, United States

Location

University Clinical Research - DeLand, LLC

DeLand, Florida, 32720, United States

Location

Pulmonary Medicine and Critical Care

Austell, Georgia, 30106, United States

Location

Sneeze, Wheeze & Itch Associates, LLC

Normal, Illinois, 61761, United States

Location

Commonwealth BioMedical Research

Madisonville, Kentucky, 42431, United States

Location

North Carolina Clinical Research

Raleigh, North Carolina, 27607, United States

Location

New Horizons Clinical Research

Cincinnati, Ohio, 45242, United States

Location

Lynn Health Science Institute

Oklahoma City, Oklahoma, 73112, United States

Location

Clinical Research Institute of Southern Oregon, PC

Medford, Oregon, 97504, United States

Location

Asthma Allergy Associates

Portland, Oregon, 97213, United States

Location

Spartanburg Medical Research

Spartanburg, South Carolina, 29303, United States

Location

Reichman Associates

Sugar Land, Texas, 77074, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Related Publications (11)

• 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.

  PMID: 17352511 BACKGROUND

• 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.

  PMID: 16022567 BACKGROUND

• 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.

  PMID: 9443940 BACKGROUND

• 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.

  PMID: 15655502 BACKGROUND

• 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.

  PMID: 16533614 BACKGROUND

• 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.

  PMID: 7965739 BACKGROUND

• 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.

  PMID: 7820105 BACKGROUND

• 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.

  PMID: 1359974 BACKGROUND

• 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.

  PMID: 1687479 BACKGROUND

• 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.

  PMID: 10537229 BACKGROUND

• 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.

  PMID: 9638577 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

carmoterol; Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Study Officials

• Donald P. Tashkin, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Steven E. Linberg, PhD

  Chiesi Farmaceutici S.p.A.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 18, 2008
• First Posted: March 21, 2008
• Study Start: April 1, 2008
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: August 27, 2010

Record last verified: 2010-08

Locations

US (15)