Dose Finding Study of CHF 4226 for Treating Patients With COPD

Sponsor

Chiesi Farmaceutici S.p.A. (Industry)

Overall Status

Completed

CT.gov ID

NCT00605891

Collaborator

Chiesi USA, Inc. (Industry)

278

Enrollment

Locations

Arms

Duration (Months)

5.6

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: carmoterol (CHF 4226) Drug: carmoterol (CHF 4226) Drug: carmoterol (CHF 4226) Drug: salmeterol Drug: placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

278 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Study Start Date :

Oct 1, 2006

Actual Primary Completion Date :

Jun 1, 2007

Actual Study Completion Date :

Jun 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A carmoterol (CHF 4226) 1.0 μg once a day, in the morning	Drug: 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)) Other Names: CHF 4226
Experimental: B carmoterol (CHF 4226) 2.0 μg once a day, in the morning	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) Other Names: CHF 4226
Experimental: C carmoterol (CHF 4226) 4.0 μg once a day, in the morning	Drug: 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) Other Names: CHF 4226
Placebo Comparator: D Placebo once a day, in the morning	Drug: placebo Placebo pMDI once a day, in the morning (1 puff of placebo pMDI + 1 puff of placebo pMDI)
Active Comparator: E Salmeterol 50 μg BID, in the morning and in the evening	Drug: salmeterol Salmeterol 50 μg DPI, in the morning and in the evening (1 blister BID) Other Names: Serevent® Diskus®/Accuhaler®

Outcome Measures

Primary Outcome Measures

Change in FEV1 [Day 1 to Day 14 (+3 days)]

Secondary Outcome Measures

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clopton Clinic	Jonesboro	Arkansas	United States	72401
2	ABM Research Center	Fresno	California	United States	93720
3	UCSD - Clinical Trials Center	San Diego	California	United States	92103
4	Institute of Healthcare Assessment Inc.	San Diego	California	United States	92120
5	National Jewish Medical and Research Center	Denver	Colorado	United States	80206
6	Clinical Research of West Florida	Clearwater	Florida	United States	33765
7	University Clinical Research - DeLand, LLC	DeLand	Florida	United States	32720
8	Clinical Research of West Florida, Inc.	Tampa	Florida	United States	33603
9	Palm Beach Research Center	West Palm Beach	Florida	United States	33409
10	Edward Hospital and Helath Services, Center for Clinical Trials	Naperville	Illinois	United States	60540
11	Community Clinical Research Center	Anderson	Indiana	United States	46011
12	ClinSite, LLC	Ann Arbor	Michigan	United States	48106
13	ClinSite	Canton	Michigan	United States	48187
14	Delaware Valley Clinical Research	Cherry Hill	New Jersey	United States	08003
15	Carolina Pharmaceutical Research	Statesville	North Carolina	United States	28625
16	New Horizons Clinical Research	Cincinnati	Ohio	United States	45242
17	Toledo Center for Clinical Research	Sylvania	Ohio	United States	43560
18	Clinical Research Institute of Southern Oregon PC	Medford	Oregon	United States	97504
19	Pulmonary Consultants - Research Department	Medford	Oregon	United States	97504
20	Lowcountry Lung and Critical Care, PA	North Charleston	South Carolina	United States	29406
21	Amarillo Center for Clinical Research, Ltd.	Amarillo	Texas	United States	79124
22	Breath of Life Research Institute	Katy	Texas	United States	77450
23	The University of Texas Health Center at Tyler	Tyler	Texas	United States	75708
24	University of Wisconsin-Allergy/Asthma	Madison	Wisconsin	United States	53792
25	Ordinace pro nemoci dychaciho ustroji	Beroun		Czech Republic	266 01
26	OTRAN	Kutna Hora		Czech Republic	284 01
27	Plicni a alergologicka ambulance	Kutna Hora		Czech Republic	284 01
28	Pneumolog, internista	Lovosice		Czech Republic	310 02
29	Plicni ambulance	Praha 3 - Zizkov		Czech Republic	130 00
30	Nemocnice Na Homolce Plicni ambulance	Praha 5		Czech Republic	15030
31	Plicni ambulance Rokycany	Rokycany		Czech Republic	337 01
32	Medars GmbH	Berlin		Germany	14057
33	Lungenzentrum Geesthacht	Geesthacht		Germany	21502
34	Pneumologisches Forschungsinstitut GmbH	Grosshansdorf		Germany	22927
35	Pneumologisches Forschungsinstitut Niederlassung Hamburg	Hamburg		Germany	20535
36	Robert-Koch-Klinik	Leipzig		Germany	04207
37	SMO, MD GmbH	Magdeburg		Germany	39112
38	IFG GmbH	Ruedersdorf		Germany	15565
39	Medcare Specjalistyczna Opieka Medyczna NZOZ	Gdansk		Poland	80-433
40	NZOZ Non-nocere	Gdansk		Poland	80-847
41	Klinika Pulmonologii i Alergologii	Lodz		Poland	90-153
42	SPZOZ w Proszowicach Oddzial Chorob Pluc	Proszowice		Poland	32-100
43	Spitalul Clinic Judetean de Urgenta Brasov	Brasov		Romania	500326
44	Spitalul de Urgenta "Prof. Dr. Dimitrie Gerota"	Bucharest		Romania	010457
45	Spitalul Clinic de Urgenta Militar Central "Davila"	Bucharest		Romania	010825
46	Spitalul Clinic "Sf. Maria"	Bucharest		Romania	011172
47	Institutul National de Pneumoftisiologie "M. Nasta"	Bucharest		Romania	050159
48	Spitalul de Pneumoftiziologie Constanta	Constanta		Romania	900002
49	UCT Lung Institute	Mowbray	Cape Town	South Africa	7700
50	Tiervlei Trial Center, Karl Bremer Hospital	Bellville		South Africa	7530