Efficacy and Safety of NVA237 in Patients With Chronic Obstructive Pulmonary Disease (COPD)

NCT01119950 | Completed Phase 2 Results

• 2 other identifiers: CNVA237A22082009-014038-11
• Study Type: interventional
• Target: 388
• Locations: 7 countries
• Sites: 29

Brief Summary

This study was designed to investigate the efficacy and safety of NVA237, a long-acting muscarinic antagonist, in patients with moderate to severe COPD.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD

Outcome Measures

Primary Outcomes (1)

• Maximal Response of Incremental Once Daily and Twice Daily Doses of NVA237 That Each Dose Achieves in Relation to the Maximal Effect of NVA237 on Trough Forced Expiratory Volume in One Second at Day 28

  Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. The maximal response of incremental once daily and twice daily doses of NVA237 that each dose achieves in relation to the maximal effect of NVA237 on Trough FEV1 was measured at Day 28. FEV1 was measured in response to all doses administered (see Outcome Measure #19). All trough FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All trough FEV1 data are reported as a percentage of the theoretical maximal response. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values.

  Day 28

Secondary Outcomes (17)

• Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237

  day 28

• Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment

  5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28

• Forced Expiratory Volume in One Second AUC 0-24 Hours for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237, After 28 Days of Treatment

  -25 min,-15 min (predose); 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28

• Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28

  5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28

• Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours at Day 28 of Treatment

  12 hours on day 28

Other Outcomes (15)

• Trough Forced Expiratory Volume in One Second by Treatment at Day 28

  Day 28

• Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment

  5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28

• Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours)

  5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28

Study Arms (8)

NVA237 12.5 µg q.d.

EXPERIMENTAL

NVA237 12.5 µg once daily

Drug: NVA237 12.5 µg once daily

NVA237 25.0 µg q.d.

EXPERIMENTAL

NVA237 25.0 µg once daily

Drug: NVA237 25.0 µg once daily

NVA237 12.5 µg b.i.d.

EXPERIMENTAL

NVA237 12.5 µg twice daily

Drug: NVA237 12.5 µg twice daily

NVA237 50.0 µg q.d.

EXPERIMENTAL

NVA237 50.0 µg once daily

Drug: NVA237 50.0 µg once daily

NVA237 25.0 µg b.i.d.

EXPERIMENTAL

NVA237 25.0 µg twice daily

Drug: NVA237 25.0 µg twice daily

NVA237 100.0 µg q.d.

EXPERIMENTAL

NVA237 100.0 µg once daily

Drug: NVA237 100.0 µg once daily

NVA237 50.0 µg b.i.d.

EXPERIMENTAL

NVA237 50.0 µg twice daily

Drug: NVA237 50.0 µg twice daily

Placebo

PLACEBO COMPARATOR

Placebo to NVA237 once daily

Drug: Placebo to NVA237 once daily

Interventions

NVA237 12.5 µg once daily DRUG

NVA237 12.5 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.

NVA237 12.5 µg q.d.

NVA237 25.0 µg once daily DRUG

NVA237 25.0 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.

NVA237 25.0 µg q.d.

NVA237 12.5 µg twice daily DRUG

NVA237 12.5 µg via dry powder inhaler twice daily for 28 days during either period 1 or during period 2.

NVA237 12.5 µg b.i.d.

NVA237 50.0 µg once daily DRUG

NVA237 50.0 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.

NVA237 50.0 µg q.d.

NVA237 25.0 µg twice daily DRUG

NVA237 25.0 µg via dry powder inhaler twice daily for 28 days during either period 1 or during period 2.

NVA237 25.0 µg b.i.d.

NVA237 100.0 µg once daily DRUG

NVA237 100.0 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.

NVA237 100.0 µg q.d.

NVA237 50.0 µg twice daily DRUG

NVA237 50.0 µg via dry powder inhaler twice daily for 28 days during either period 1 or during period 2.

NVA237 50.0 µg b.i.d.

Placebo to NVA237 once daily DRUG

Placebo to NVA237 via dry powder inhaler once daily for 28 days during either period 1 or during period 2.

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients age 40 years or more
• Diagnosis of Chronic Obstructive Lung Disease (COPD) (moderate to severe as classified by the Global Initiative for COPD (GOLD) Guidelines, 2008
• Smoking history of at least 10 pack-years
• Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) \<80% and ≥30% of the predicted normal value
• Post-bronchodilator FEV1/Forced Vital Capacity (FVC) \<0.7
• Symptomatic patients, according to daily electronic diary data between visit 2 (Day -8) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to visit 3

You may not qualify if:

• Patients who have had a COPD exacerbation requiring systemic corticosteroids and/or antibiotics and/or hospitalization in the 6 weeks prior to the first visit
• Patients who have had a respiratory tract infection within 4 weeks prior to the first visit
• Patients with concomitant pulmonary disease
• Patients with diabetes Type I or uncontrolled diabetes Type II
• Any patient with lung cancer or a history of lung cancer
• Patients with a history of certain cardiovascular co-morbid conditions
• Patients with a history of asthma or a blood eosinophil count \>600/mm3 or onset of symptoms prior to 40 years
• Patients with eczema, known high IgE levels or a known positive skin prick test
• Patients participating in the active phase of a pulmonary rehabilitation programme
• Patients contraindicated for the treatment with anticholinergics, long and short-acting beta-2 agonists or sympathomimetic amines
• Patients with a history of alpha-1 anti-trypsin deficiency
• Patients on long term oxygen therapy (\>15hr per day)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (29)

Novartis Investigative Site

Anniston, Alabama, 36201, United States

Location

Novartis Investigative Site

San Diego, California, 92101, United States

Location

Novartis Investigative Site

Torrance, California, 90501, United States

Location

Novartis Investigative Site

Denver, Colorado, 80012, United States

Location

Novartis Investigative Site

Omaha, Nebraska, 68104, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19102, United States

Location

Novartis Investigative Site

Antwerp, Belgium

Location

Novartis Investigative Site

Genk, Belgium

Location

Novartis Investigative site

Jambes, Belgium

Location

Novartis Investigative Site

München, Germany

Location

Novartis Investigative Site

Balassagyarmat, Hungary

Location

Novartis Investigative Site

Balatonfüred, Hungary

Location

Novartis Investigative Site

Budapest, Hungary

Location

Novartis Investigative Site

Debrecen, Hungary

Location

Novartis Investigative Site

Szolnok, Hungary

Location

Novartis Investigative Site

Törökbálint, Hungary

Location

Novartis Investigative Site

Almelo, Netherlands

Location

Novartis Investigative Site

Eindhoven, Netherlands

Location

Novartis Investigative Site

Harderwijk, Netherlands

Location

Novartis Investigative Site

Heerlen, Netherlands

Location

Novartis Investigative Site

Helmond, Netherlands

Location

Novartis Investigative Site

Veldhoven, Netherlands

Location

Novartis Investigative Site

Zutphen, Netherlands

Location

Novartis Investigative Site

Izabelin, Poland

Location

Novartis Investigative Site

Lodz, Poland

Location

Novartis Investigative Site

Warsaw, Poland

Location

Novartis Investigative Site

A Coruña, Spain

Location

Novartis Investigative Site

Alicante, Spain

Location

Novartis Investigative Site

Ponferrada, Spain

Location

Related Publications (1)

• Arievich H, Overend T, Renard D, Gibbs M, Alagappan V, Looby M, Banerji D. A novel model-based approach for dose determination of glycopyrronium bromide in COPD. BMC Pulm Med. 2012 Dec 8;12:74. doi: 10.1186/1471-2466-12-74.

  PMID: 23217058 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Glycopyrrolate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

41 61 324 1111

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2010
• First Posted: May 10, 2010
• Study Start: April 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: March 23, 2015
• Results First Posted: April 15, 2014

Record last verified: 2015-03

Locations

NL (7); PL (3); BE (3); DE (1); HU (6); ES (3); US (6)