A Study to Measure the Lung Response to Different Doses of a New Medicine for COPD

• Register: EUCTR
• Last refreshed on: 28 November 2016
• Main ID: EUCTR2014-000883-16-PL
• Date of registration: 10/06/2014
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Devlopment Ltd
• Public title: A Study to Measure the Lung Response to Different Doses of a New Medicine for COPD
• Scientific title: A Clinical Study to Evaluate Four Doses of Umeclidinium Bromide in Combination with Fluticasone Furoate in COPD Subjects with an Asthmatic Component
• Date of first enrolment: 19/07/2014
• Target sample size: 450
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000883-16
• 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: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: (Fluticasone Furoate/Vilanterol), Fluticasone Furoate Number of treatment arms in the trial: 12
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Germany, Poland, Romania, Russian Federation, 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:
1.Age: 18 years of age or older at Visit 0
2.Diagnosis: At the point of screening subjects, have sufficient medical
history (e.g., signs and symptoms) to diagnose the subject as having
COPD in accordance with the definition by the American Thoracic
Society/European Respiratory Society (Celli, 2004), AND evidence of an
asthmatic component as demonstrated by spirometry, reversibility and
current therapy at Visit 1 as follows:
A.Spirometry:
1.A best post-bronchodilator morning (AM) FEV1 =50% and =80% of
the predicted normal value at Visit 1 will be based upon the ERS Global
Lung Function Initiative.
AND
2. Pre- and post-bronchodilator FEV1/FVC ratio <0.7 at Visit 1.
B. Reversibility of Disease: defined as: =12% and =200 mL increase in FEV1 between 20 and 60 minutes following 4 inhalations of albuterol/salbutamol aerosol at Visit 1. If a subject fails to demonstrate an increase in FEV1 =12% and =200 mL at Visit 1, then the subject will not be allowed to repeat spirometry at a subsequent visit to determine eligibility.
C. Current Therapy: Subjects are eligible if they have received ICS-containing therapy for at least 12 weeks prior to Visit 1 and if their treatment during the 4 weeks immediately prior to Visit 1 consisted of either of the two regimens (1 or 2) below.
1. A stable ICS dose taken alone (e.g., FP =200-1000 mcg daily or equivalent dose)
OR
2. A stable dose of ICS (e.g., FP =500 mcg daily or equivalent dose) with adjunctive therapy (i.e., LABA, LAMA, leukotriene receptor antagonists [LTRA], theophylline, etc.). Subjects taking Symbicort as needed must switch to Symbicort maintenance dosing with as-needed use of a short acting
beta2 agonist (SABA) for symptom relief at least 4 weeks prior to Visit 1. Examples of acceptable doses of commonly prescribed ICS and ICS/LABA combination medication will be provided. Dosing regimen (once or twice daily to equal the total daily dose) should be restricted to the current local product labels.
3. Short-Acting ß2 Agonists (SABAs): All subjects must be able to replace their current SABA inhaler with albuterol/salbutamol aerosol inhaler at Visit 1 as needed for the duration of the study. Subjects may instead use their own nebulized albuterol/salbutamol as needed, if this method is preferred. Subjects must be judged capable of withholding albuterol/salbutamol for at least 4 hours prior to study visits.
4. Type of Subject: Outpatient subjects who are smokers or non-smokers
5. Gender: Male or Eligible Female, defined as having documentation of nonchildbearing potential or childbearing potential as follows:
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 use an acceptable contraceptive method 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).
The following is the GSK list of acceptable, highly effective methods for avoiding pregnancy wit
Exclusion criteria:
1. History of Life-threatening Respiratory Event: Defined for this protocol as an episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures within the last 5 years.
2. Respiratory Infection: Any infection of the upper or lower respiratory tract, sinus, or middle ear that is not resolved within 4 weeks of Visit 1 and led to a change in COPD/asthma management or, in the opinion of the investigator, is expected to affect the subject’s COPD/asthma status or the subject’s ability to participate in the study.
3. Severe Exacerbation: A subject must not have had an exacerbation
prior to Visit 1 meeting either of the following criteria:
- Deterioration of COPD or asthma requiring either the use of oral
corticosteroids for at least 3 days or parenteral corticosteroids in the
previous 3 months.
- An in-patient hospitalization or emergency department visit due to
COPD or asthma that required any oral or parenteral corticosteroids in the previous 6 months
For consistency, courses of corticosteroids separated by 1 week or more
should be treated as separate exacerbations.
4. Risk Factors for Pneumonia: Immune suppression (e.g., Human Immunodeficiency Virus [HIV], Lupus) or other risk factors for pneumonia (e.g.,neurological disorders affecting control of the upper airway, such as Parkinson’s Disease, Myasthenia Gravis). Please view protocol for further information.
5. Pneumonia: Hospitalization for pneumonia within 3 months prior to Visit 1.
6. Concurrent Respiratory Disease: A subject must not have current evidence of the following: pneumonia, pneumothorax, atelectasis (segmental or larger), pulmonary fibrotic disease, bronchopulmonary dysplasia, or other respiratory abnormalities other than chronic obstructive pulmonary disease (including chronic bronchitis and emphysema) or asthma. Please view protocol for further information.
7. Other Concurrent Diseases/Abnormalities: A subject must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation. Please view protocol for further information.
8. Viral Hepatitis and HIV: A positive Hepatitis B surface antigen or positive Hepatitis C antibody pre-study or at Visit 1. Subjects with HIV-positive history are not eligible.
9. Hepatic Impairment: Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones).
10. Allergies:
- Drug Allergy: Any immediate or delayed hypersensitivity reaction to a ß2 agonist, sympathomimetic drug, corticosteroid please view protocol for further information.
11. Concomitant Medication: Administration of prescription or over-the-counter medication that would significantly affect the course of COPD or asthma, or interact with study drug, please view protocol for further information.
12. Lung Resection: Subjects with lung volume reduction surgery within 12 months prior to Visit 1.
13. Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (i.e., =12 hours per day) is not exclusionary.
14. Nebulized Therapy: Regular use (prescribed for use every day) of short-acting bronchodilators (e.g., albuterol/salbutamol) via nebulized therapy. As-needed nebulized albuterol/salbutamol use is not exclusionary.
15. Pul

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

Health Condition(s) or Problem(s) studied

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

COPD Subjects with an Asthmatic Component
MedDRA version: 18.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
MedDRA version: 18.0 Level: LLT Classification code 10009028 Term: Chronic obstructive asthma (with obstructive pulmonary disease) System Organ Class: 100000004855

Intervention(s)

Product Name: Fluticasone Furoate / umeclidinium
Product Code: Fluticasone Furoate / umeclidinium
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: FLUTICASONE FUROATE
CAS Number: 397864-44-7
Current Sponsor code: GW685698
Other descriptive name: (6 alpha,11 beta,16 alpha,17alpha)-6,9-Difluoro-17-{[(fluoromethyl)thio]carbonyl}-11-hydroxy-16-methyl-3-oxoandrosta-1,4-dien-17-yl 2 furancarboxylate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: Umeclidinium Bromide
CAS Number: 869113-09-7
Current Sponsor code: GSK573719A
Other descriptive name: 1-[2-(Benzyloxy)ethyl]-4-(hydroxydiphenylmethyl)-1-azoniabicyclo[2.2.2]octane bromide
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 15.6-

Product Name: Fluticasone Furoate / umeclidinium
Product Code: Fluticasone Furoate / umeclidinium
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: FLUTICASONE FUROATE
CAS Number: 397864-44-7
Current Sponsor code: GW685698
Other descriptive name: (6alpha,11Beta,16alpha,17alpha)-6,9-Difluoro-17-{[(fluoromethyl)thio]carbonyl}-11-hydroxy-16-methyl-3-oxoandrosta-1,4-dien-17-yl 2 furancarboxylate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: Umeclidinium Bromide
CAS Number: 869113-09-7
Current Sponsor code: GSK573719A
Other descriptive name: 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-

Product Name: Fluticasone Furoate / umeclidinium
Product Code: Fluticasone Furoate / umeclidinium
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: FLUTICASONE FUROATE
CAS Number: 397864-44-7
Current Sponsor code: GW685698
Other descriptive name: (6alpha,11Beta,16alpha,17alpha)-6,9-Difluoro-17-{[(fluoromethyl)thio]carbonyl}-11-hydroxy-16-methyl-

Primary Outcome(s)

Secondary Objective: To evaluate the treatment effect of FF/UMEC compared to the combination of FF and VI over a 4-week treatment period in COPD subjects with an asthmatic
component.
Exploratory Objective(s)
- To evaluate the treatment effect of VI in COPD subjects with an asthmatic
component treated with FF/UMEC
- To evaluate the effect on lung function of discontinuing UMEC in COPD subjects with an asthmatic component
- To explore the relationship of patient reported outcomes (PROs) with patient
characteristics such as level of reversibility and obstruction, diagnosis and other measures of disease severity
- To explore the responsiveness of PRO measures to response on other outcomes and determine potential responder definitions
- To determine differential responses and their phenotypic characteristics by
exploratory and subgroup analyses
Other Objective(s)
- To evaluate the safety of FF/UMEC therapy

Primary end point(s): Change from baseline in clinic trough (pre-dose) FEV1 at the end of Treatment Phase A

Main Objective: The primary objective is to evaluate the dose-response of once-daily
UMEC in combination with FF (100/15.6, 100/62.5, 100/125,
and 100/250 mcg) compared to FF 100 mcg monotherapy
over a 4-week treatment period in COPD subjects with an
asthmatic component.

Timepoint(s) of evaluation of this end point: Visit 3 (baseline) and Visit 6 (Week 4, Day 29)

Secondary Outcome(s)

Secondary end point(s): Mean change from baseline in rescue medication use at the end of Treatment Phase A
Mean change from baseline in EXACT-RS score at the end of Treatment Phase A
Change from baseline in daily morning (AM) PEF (pre-dose and pre-rescue bronchodilator) measured at home and averaged over the last 21 days of Treatment Phase A
Change from trough in FEV1 at 3 hours post-study treatment at Visit 5
Change in clinic FEV1 following 2 puffs of albuterol/salbutamol given 3 hours post-study treatment dose at Visit 5

Timepoint(s) of evaluation of this end point: Day 28 and Day 29

Secondary ID(s)

200699

2014-000883-16-DE

Source(s) of Monetary Support

GSK