To demonstrate the superiority of indacaterol 150 µg o.d. in combination with tiotropium 18 µg o.d. versus tiotropium 18 µg o.d. with respect to standardized area under the curve (AUC) for forced expiratory volume in 1 second (FEV1) between 5 min *…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Standardized area under the curve (AUC) between 5 min and 8 h post-dose for
forced expiratory volume in 1 second (FEV1) after 12 weeks of treatment.
Secondary outcome
# Efficacy
Key: 24 hour post-dose trough FEV1 after 12 weeks of treatment. The 24 h
post-dose trough FEV1 is defined as the avarage of FEV1 measurements at 23 h 10
min and 23 h 45 min post-dose.
Other: Standardized AUC 5min-8h FEV1 on Day 1, Standardized AUC 5min-4h FEV1 on
Day 1 and after 12 weeks treatment,
Trough FEV1 on Day 2, FEV1 and FVC at individual time points, Peak FEV1 during
4 h post dose, Inspiratory Capacity, Symptom scores over 12 weeks, Daily Rescue
Medication use (number of puffs) over 12 weeks, Daily rescue medication use
(number of puffs) at 4 weekly intervals, Percentage of *days with no rescue
use* over 12 weeks.
# Safety
Adverse events, ECG and vital signs, laboratory data
Background summary
This study will provide 12 weeks of comparative efficacy and safety data on
indacaterol (150 µg o.d.) combined with tiotropium (18 µg o.d.) versus
tiotropium (18 µg o.d.) alone. This data will support GOLD guidelines
recommendations that suggest combining two bronchodilators with complementary
actions on airways may increase and sustain bronchodilation in patients with
chronic obstructive pulmonary disease (COPD).
Study objective
To demonstrate the superiority of indacaterol 150 µg o.d. in combination with
tiotropium 18 µg o.d. versus tiotropium 18 µg o.d. with respect to standardized
area under the curve (AUC) for forced expiratory volume in 1 second (FEV1)
between 5 min * 8 h post-dose after 12 weeks of treatment in patients with
moderate-to-severe COPD.
Study design
This is a 12 week, multicenter, randomized, double-blind, controlled, parallel
group study. At the pre-screening Visit 1 informed consent is obtained and
current COPD medications are reviewed and adjusted if necessary (washout period
of approximately one week). Then begins a screening/run-in period of 14 days.
Patients whose elegibility is confirmed after the screening/run-in period will
be randomized to one of two treatment groups using an allocation ratio of 1:1.
The randomization will be stratified by COPD severity (moderate or severe, as
classified by the GOLD Guidelines, 2007).
Intervention
Patients will be assigned to one of the following 2 treatment arms in a ratio
of 1:1
1. Indacaterol 150 µg o.d. + open label tiotropium 18µg o.d.
2. Placebo to indacaterol + open label tiotropium 18µg o.d.
At visit 1 all patients will be provided with salbutamol which they will be
instructed to use throughout the study as rescue medication.
Study burden and risks
Burden:
The patient will be asked to come to the clinic for a visit 9 times over about
15 weeks and take two capsules study medication once a day for 12 treatment
weeks. The study medication is inhaled by using a different inhaler for each
capsule. A serum pregnancy test will be done 2x (when applicable), 2x a
physical exam, at 3 visits ECGs will be made (in total 11x), at 7 visits
bloodpressure and pulse rate are measured (in total 9x), at 3 visits urine is
tested, at 3 visits blood samples are taken (in total at 5 timepoints), at 8
visits long function tests are done including 2x a reversibility test and at 2
days measurements up to 8 hours postdose (in total 28x). Furthermore, the
patient will be asked to complete an electronic diary twice daily.
Risks:
Possible side effects of the study medicine indacaterol (QAB149) can include:
tremor, headache, cough, post-inhalation cough, palpitations, muscle cramps,
nausea, chest pain, trouble sleeping, nervousness, dry mouth, dizziness,
tiredness, feeling generally unwell and possible changes in blood pressue or
potassium or blood sugar.
Side effects of the other study medicine, tiotropium (Spiriva®), include: dry
mouth, constipation, tremor, headache, palpitations, blurred vision, glaucoma,
urinary difficulty, urinary retention, muscle cramps and nausea.
Unexpected problems or side effects that are not known could also occur.
Taking blood and measuring blood pressure could be unpleasant. The risks of
taking blood may include fainting, pain and/or bruising. Rarely, these may be a
small blood clot or infection at the site of the needle puncture. In rare
instances where a nurse, a doctor, or laboratory technician, sustains an
exposure to a patients blood, it may be necessary to test the blood for
Hepatitis-B, Hepatitis-C and HIV.
Raapopseweg 1
6824 DP
Nederland
Raapopseweg 1
6824 DP
Nederland
Listed location countries
Age
Inclusion criteria
1. Male and female adults aged 40 years and over
2. Co-operative outpatients with a diagnosis of COPD (moderate to severe as classified by the GOLD Guidelines, 2007) and including:
a) Smoking history of at least 10 pack years, both current and ex-smokers are eligible
b) Post-bronchodilator FEV1 * 65% and * 30% of the predicted normal value
c) Post-bronchodilator FEV1/FVC < 70%
Exclusion criteria
For a complete list please see protocol section 5.2.
#. Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid treatment or antibiotics and/or hospitalization in the 6 weeks prior to screening (Visit 2).
#. Patients requiring oxygen therapy for chronic hypoxemia.
#. Patients who have had a respiratory tract infection within 6 weeks prior to Visit 2.
#. Patients with a history (up to and including Visit 2) of asthma indicated by (but not limited to):
a) onset of respiratory symptoms suggestive of asthma prior to age 40 years
b) history of a diagnosis of asthma
#. Patients with diabetes Type I or uncontrolled diabetes Type II including patients with a history of blood glucose levels consistently outside the normal range or HbA1c > 8.0 % of total hemoglobin measured at Visit 2.
#. Patients with a history (or family history) of long QT syndrome or whose QTc interval (Fridericia) measured at Visit 2 is prolonged.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-008447-26-NL |
| CCMO | NL26334.096.09 |