Dose Finding Study of CHF 4226 for Treating Patients With COPD

NCT00605891 | Completed Phase 2

• 2 other identifiers: US/PR/033009/001/05EudraCT Number: 2006-000531-10
• Study Type: interventional
• Target: 278
• Locations: 6 countries
• Sites: 50

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.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• Change in FEV1

  Day 1 to Day 14 (+3 days)

Secondary Outcomes (5)

• FEV1

  10 and 30 min, 1, 2, and 3 hrs post dose on Day 1, Day 2 and Day 14 (+3)

• ECG/QTc

  pre dose and post dose at 30' on Days 1, 2 and 14 (+3)

• Fasting serum potassium

  pre dose and post dose at 30' on Days 1, 2 and 14 (+3)

• Fasting glucose

  pre dose and post dose at 30' on Days 1, 2 and 14 (+3)

• Change in FEV1

  10 and 30 min, 1, 2, and 3 hrs post dose on Day 1, Day 2 and Day 14 (+3)

Study Arms (5)

A

EXPERIMENTAL

carmoterol (CHF 4226) 1.0 μg once a day, in the morning

Drug: carmoterol (CHF 4226)

B

EXPERIMENTAL

carmoterol (CHF 4226) 2.0 μg once a day, in the morning

Drug: carmoterol (CHF 4226)

C

EXPERIMENTAL

carmoterol (CHF 4226) 4.0 μg once a day, in the morning

Drug: carmoterol (CHF 4226)

D

PLACEBO COMPARATOR

Placebo once a day, in the morning

Drug: placebo

E

ACTIVE COMPARATOR

Salmeterol 50 μg BID, in the morning and in the evening

Drug: salmeterol

Interventions

carmoterol (CHF 4226) DRUG

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)

Also known as: CHF 4226

B

salmeterol DRUG

Salmeterol 50 μg DPI, in the morning and in the evening (1 blister BID)

Also known as: Serevent® Diskus®/Accuhaler®

E

placebo DRUG

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

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:

• 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%

You may not qualify if:

• 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)

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead
• Chiesi USA, Inc.: collaborator

Study Sites (50)

Clopton Clinic

Jonesboro, Arkansas, 72401, United States

Location

ABM Research Center

Fresno, California, 93720, United States

Location

UCSD - Clinical Trials Center

San Diego, California, 92103, United States

Location

Institute of Healthcare Assessment Inc.

San Diego, California, 92120, United States

Location

National Jewish Medical and Research Center

Denver, Colorado, 80206, United States

Location

Clinical Research of West Florida

Clearwater, Florida, 33765, United States

Location

University Clinical Research - DeLand, LLC

DeLand, Florida, 32720, United States

Location

Clinical Research of West Florida, Inc.

Tampa, Florida, 33603, United States

Location

Palm Beach Research Center

West Palm Beach, Florida, 33409, United States

Location

Edward Hospital and Helath Services, Center for Clinical Trials

Naperville, Illinois, 60540, United States

Location

Community Clinical Research Center

Anderson, Indiana, 46011, United States

Location

ClinSite, LLC

Ann Arbor, Michigan, 48106, United States

Location

ClinSite

Canton, Michigan, 48187, United States

Location

Delaware Valley Clinical Research

Cherry Hill, New Jersey, 08003, United States

Location

Carolina Pharmaceutical Research

Statesville, North Carolina, 28625, United States

Location

New Horizons Clinical Research

Cincinnati, Ohio, 45242, United States

Location

Toledo Center for Clinical Research

Sylvania, Ohio, 43560, United States

Location

Clinical Research Institute of Southern Oregon PC

Medford, Oregon, 97504, United States

Location

Pulmonary Consultants - Research Department

Medford, Oregon, 97504, United States

Location

Lowcountry Lung and Critical Care, PA

North Charleston, South Carolina, 29406, United States

Location

Amarillo Center for Clinical Research, Ltd.

Amarillo, Texas, 79124, United States

Location

Breath of Life Research Institute

Katy, Texas, 77450, United States

Location

The University of Texas Health Center at Tyler

Tyler, Texas, 75708, United States

Location

University of Wisconsin-Allergy/Asthma

Madison, Wisconsin, 53792, United States

Location

Ordinace pro nemoci dychaciho ustroji

Beroun, 266 01, Czechia

Location

OTRAN

Kutná Hora, 284 01, Czechia

Location

Plicni a alergologicka ambulance

Kutná Hora, 284 01, Czechia

Location

Pneumolog, internista

Lovosice, 310 02, Czechia

Location

Nemocnice Na Homolce Plicni ambulance

Prague, 15030, Czechia

Location

Plicni ambulance

Praha 3 - Zizkov, 130 00, Czechia

Location

Plicni ambulance Rokycany

Rokycany, 337 01, Czechia

Location

Medars GmbH

Berlin, 14057, Germany

Location

Lungenzentrum Geesthacht

Geesthacht, 21502, Germany

Location

Pneumologisches Forschungsinstitut GmbH

Großhansdorf, 22927, Germany

Location

Pneumologisches Forschungsinstitut Niederlassung Hamburg

Hamburg, 20535, Germany

Location

Robert-Koch-Klinik

Leipzig, 04207, Germany

Location

SMO, MD GmbH

Magdeburg, 39112, Germany

Location

IFG GmbH

Rüdersdorf, 15565, Germany

Location

Medcare Specjalistyczna Opieka Medyczna NZOZ

Gdansk, 80-433, Poland

Location

NZOZ Non-nocere

Gdansk, 80-847, Poland

Location

Klinika Pulmonologii i Alergologii

Lodz, 90-153, Poland

Location

SPZOZ w Proszowicach Oddzial Chorob Pluc

Proszowice, 32-100, Poland

Location

Spitalul Clinic Judetean de Urgenta Brasov

Brasov, 500326, Romania

Location

Spitalul de Urgenta "Prof. Dr. Dimitrie Gerota"

Bucharest, 010457, Romania

Location

Spitalul Clinic de Urgenta Militar Central "Davila"

Bucharest, 010825, Romania

Location

Spitalul Clinic "Sf. Maria"

Bucharest, 011172, Romania

Location

Institutul National de Pneumoftisiologie "M. Nasta"

Bucharest, 050159, Romania

Location

Spitalul de Pneumoftiziologie Constanta

Constanța, 900002, Romania

Location

UCT Lung Institute

Mowbray, Cape Town, 7700, South Africa

Location

Tiervlei Trial Center, Karl Bremer Hospital

Bellville, 7530, South Africa

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

• 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

• 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

Related Links

• Study Record on EU Clinical Trials Register including results

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

• Barry Make, MD

  National Jewish Medical & Research Center

  PRINCIPAL INVESTIGATOR

• Steven E Linberg, Ph.D.

  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: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 18, 2008
• First Posted: January 31, 2008
• Study Start: October 1, 2006
• Primary Completion: June 1, 2007
• Study Completion: June 1, 2007
• Last Updated: April 11, 2017

Record last verified: 2017-04

Locations

CZ (7); US (24); DE (7); RO (6); ZA (2); PL (4)