Primary objectiveTo evaluate the relationship of incremental doses of NVA237 q.d. and b.i.d. and their effect on trough FEV1 after 28 days of treatment, as defined by the percentage of the maximal effect that each dose achieves in relation to the…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Relationship of incremental doses of NVA237 q.d. and b.i.d. and their effect on
trough FEV1 after 28 days of treatment, as defined by the percentage of the
maximal effect that each dose achieves in relation to the maximal effect of
NVA237. (Trough is defined as the mean of FEV1
measurements at 23 h 15 min and 23 h 45 min post morning dose).
Secondary outcome
Use of rescue medication, FEV1 (AUC 0-24 h and shorter intervals, peak and 12
h), FVC, safety.
Background summary
NVA237 is a synthetic quaternary ammonium compound that acts as a competitive
antagonist at muscarinic
acetylcholine receptors and is being developed as a once-daily inhalation
treatment to be delivered by the Novartis
Single Dose Dry Powder Inhaler (SDDPI) for patients with COPD. Inhaled
anticholinergic drugs such as ipratrompium
bromide (Atrovent®) and Tiotropium bromide (Spiriva®) have been approved in the
US and European Union for the
treatment of COPD.
This study is designed to support the registration of NVA237 worldwide,
including the US and the EU.
Study objective
Primary objective
To evaluate the relationship of incremental doses of NVA237 q.d. and b.i.d. and
their effect on trough FEV1 after 28 days of treatment, as defined by the
percentage of the maximal effect that each dose achieves in relation to the
maximal effect of NVA237. (Trough is defined as the mean of FEV1 measurements
at 23 h 15 min and 23 h 45 min post morning dose).
Key secondary objective
To evaluate the magnitude of any difference of effect on trough FEV1 after 28
days of treatment between the same total daily doses of NVA237 by comparing
once daily and twice daily dosing regimens.
Study design
Randomized, double blind, placebo controlled cross over phase II study . 8
treatments, balanced incomplete block design. qd or bid dosing. Pre-screening,
s.n. adjustment current COPD treatment, followed by 2nd screening and 1 week
run-in period. Thereafter randomization to 16 independent treatment sequences.
All patients will be given 2 treatments, separated by a washout period of 1
week.
Treatments:
1. Qd NVA237 12,5 mcg
2. Qd NVA237 25 mcg
3. Qd NVA237 50 mcg
4. Qd daags NVA237 100 mcg
5. Bid NVA237 12,5 mcg
6. BidNVA237 25 mcg
7. Bid NVA237 50 mcg
8. Placebo.
via single dose powder inhaler.
Salbutamol rescue medication.
Total study duration approx. 11 weeks.
Approx. 360 randomized patients (>500 screened).
Intervention
NVA237 or placebo.
Study burden and risks
Risks: Adverse events of study medication. Changes in current COPD medication.
Burden: 11-12 visits in 11 weeks, thereoff 6 days of 24 h measurements (incl.
hotel overnight stay) and 2 days of 9h measurements. Daily diary. Safety blood
3x.Approx. 10 ml blood per visit, total volume ca. 30 ml. Pregnancy test 2x.
Normal visits: 3x. Vital signs (plus or minus physical exam) 1 visit. Pulmonary
function tests 2x per visit (1 visit with reversibility). EKG 1 visit.
9h visits: 2x. Duration 9h. 6x pulmonary function tests. 1x vital signs.
24h visits: 6x. Duration 24h. 6x overnight stay in hotel with nightly
measurements. 14-17 pulm. function tests. 0-1 EKG and 1-3x vital signs per
visit.
Raapopseweg 1
6824 DP Arnhem
NL
Raapopseweg 1
6824 DP Arnhem
NL
Listed location countries
Age
Inclusion criteria
1. Male or female adults aged 40 years and above.
2. Moderate to severe stable COPD (Stage II or Stage III) according to the (GOLD Guidelines 2008).
3. Smoking history of at least 10 pack years.
4. Post-bronchodilator FEV1 >30% and < 80% of the predicted normal.
5. FEV1/FVC ratio <70% (post bronchodilation).
Exclusion criteria
• Lower airway infection in the past 4 weeks.
• Bronchial asthma.
• Type I and uncontrolled type II diabetes.
• α1-antitrypsin deficiency.
• Other relevant pulmonary diseases.
• Contra-indications for anticholinergics.
• Use of ceratin COPD and other medications (see protocol for details).
• Vaccination with live or inactivated vaccines in the past 30 and 2 days resp.
• Longterm oxygen therapy.
• Pregnancy and breast feeding. Inadequate contraception, if relevant.
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 |
|---|---|
| Other | clinicaltrials.gov, registratienummer nog niet bekend |
| EudraCT | EUCTR2009-014038-11-NL |
| CCMO | NL31828.060.10 |