Study to compare umeclidinium with tiotropium in COPD subjects

• Register: EUCTR
• Last refreshed on: 18 January 2016
• Main ID: EUCTR2014-000884-42-IT
• Date of registration: 17/06/2014
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Ltd
• Public title: Study to compare umeclidinium with tiotropium in COPD subjects
• Scientific title: A Randomized, Blinded, Double-dummy, Parallel-group Study to Evaluate the Efficacy and Safety of Umeclidinium (UMEC) 62.5 mcg compared with Tiotropium 18 mcg in Subjects with Chronic Obstructive Pulmonary Disease (COPD). - A Phase 3b, 12 week, study to evaluate the efficacy and safety of UMEC versus tiotropium
• Date of first enrolment: 03/07/2014
• Target sample size: 1006
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000884-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Double-dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Canada, Chile, Denmark, Germany, Italy, Korea, Republic of, Russian Federation, South Africa, Ukraine, United States

Contacts

• Name: Clinical Trials Helpdesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

• Name: Clinical Trials Helpdesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for enrolment in the study must meet all of the
following criteria:

1. Type of subject: outpatient.

2. Informed Consent: A signed and dated written informed consent prior to study participation.

3. Age: Subjects 40 years of age or older at Visit 1.

4. Gender: Male and female subjects are eligible to participate in the study.

A female is eligible to enter and participate in the study if she is of:

Non-child bearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age appropriate, > 45 years, in the absence of hormone replacement therapy.

OR

Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly (i.e., in accordance with the approved product label and the instructions of the physician for the duration of the study – screening to follow-up contact):

- Abstinence
- Oral Contraceptive, either combined or progestogen alone
- Injectable progestogen
- Implants of levonorgestrel
- Estrogenic vaginal ring
- Percutaneous contraceptive patches
- Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label
- Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject.
- Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent(foam/gel/film/cream/suppository)

5. Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004].

6. Smoking History: Current or former cigarette smokers with a history of cigarette smoking of = 10 pack-years [number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g. 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack-years)]. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Pipe and/or cigar use cannot be used to calculate pack-year history.

7. Severity of Disease: A pre and post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and a post-albuterol/salbutamol FEV1 of =30% and =70% of predicted normal values at Visit 1. Predicted values will be based upon the ERS Global Lung Function Initiative [Quanjer, 2012].

8. Dyspnea: A score of =2 on the Modified Medical Research Council Dyspnea Scale (mMRC) at Visit 1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 573
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 433

Exclusion criteria:
Subjects meeting any of the following criteria must not be enrolled in the study:

1. Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.

2. Asthma: A current diagnosis of asthma.

3. Other Respiratory Disorders: Known a-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer are absolute exclusionary conditions. A subject who, in the opinion of the investigator, has any other significant respiratory conditions in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease.

4. Other Diseases/Abnormalities: Any subject who is considered unlikely to survive the duration of the study period or has any rapidly progressing disease or immediate life-threatening illness (e.g. cancer). In addition, any subject who has any condition (e.g. neurological condition) that is likely to affect respiratory function should not be included in the study.

5. Severe Hepatic Impairment: Patients with severe hepatic impairment (Child-Pugh class C) should be excluded unless, in the opinion of the investigator, the benefit is likely to outweigh the risk.

6. Moderate to severe Renal Impairment: Patients with moderate to severe renal impairment (e.g., end-stage renal disease requiring dialysis) should be excluded, unless in the opinion of the investigator, the benefit is likely to outweigh the risk.

7. Unstable or life threatening cardiac disease: LAMAs should be used with caution in subjects with severe cardiovascular disease. In the opinion of the investigator, use should only be considered if the benefit is likely to outweigh the risk in conditions such as:

- Myocardial infarction or unstable angina in the last 6 months
- Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months
- NYHA Class IV heart failure

8. Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, sympathomimetic, lactose/milk protein or magnesium stearate.

9. Antimuscarinic effects: Subjects with medical conditions such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy, or bladder neck obstruction should only be included if, in the opinion of the study physician, the benefit outweighs the risk.

10. Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.

11. Lung Resection: Lung volume reduction surgery within the 12 months prior to Visit 1.

12. 12-Lead ECG: Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility. The Investigator will determine the clinical significance of each abnormal ECG finding in relation to the subject's medical history and exclude subjects who would be at undue risk by participating in the trial. Subjects with the following abnormalities are excluded from participation in the study:

- Atrial fibrillation with rapid ventricular rate >120 bpm
- Sustained or nonsustained ventricular tachycardia
- Second degree heart block Mobitz type II or third degree heart block (unless pacemaker or defibrillator had been inserted)

13. Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.

14. Medications Prior to Screening: U

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 17.0 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Name: Umeclidinium
Product Code: GSK573719
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: UMECLIDINIUM BROMIDE
CAS Number: 869113-09-7
Current Sponsor code: GSK573719A
Other descriptive name: GSK573719A, 1-(2-(Benzyloxy)ethyl)-4-(hydroxydiphenylmethyl)-1-azoniabicyclo(2.2.2) octane bromide
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 62.5-
Pharmaceutical form of the placebo: Inhalation powder, pre-dispensed
Route of administration of the placebo: Inhalation use

Trade Name: SPIRIVA 18 microgram, inhalation powder, hard capsule
Product Name: Tiotropium
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: TIOTROPIUM BROMIDE
CAS Number: 139404-48-1
Current Sponsor code: GSK573719A
Other descriptive name: (1a,2ß,4ß,7ß)-7-[(hydroxidi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane bromide
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 18-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Trade Name: VENTOLIN SOSP INAL 200D 100MCG
Product Name: salbutamol
Pharmaceutical Form: Inhalation solution
INN or Proposed INN: SALBUTAMOL SULFATE
CAS Number: 51022-70-9
Current Sponsor code: SB-240563
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: The primary objective of this study is to compare the efficacy and safety of UMEC 62.5 mcg with tiotropium 18 mcg in subjects with COPD over 12 weeks of treatment.

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: Day 85 (Week 12 + 1 day)

Primary end point(s): The primary efficacy endpoint is the clinic visit trough FEV1 on Treatment Day 85.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Not applicable

Secondary end point(s): None

Secondary ID(s)

2014-000884-42-DE

201316

Source(s) of Monetary Support

GlaxoSmithKline