Efficacy, Tolerability and Safety of NVA237 in Patients With Chronic Obstructive Pulmonary Disease

NCT01513460 | Completed Phase 3 Results

• 1 other identifier: CNVA237AAU01
• Study Type: interventional
• Target: 773
• Locations: 2 countries
• Sites: 71

Brief Summary

This study will assess the efficacy, tolerability and safety of NVA237 compared to tiotropium when added on to fluticasone/salmeterol in patients with chronic obstructive pulmonary disease.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Chronic Obstructive Pulmonary Disease,; NVA 237,; glycopyrronium,; COPD

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Mean Trough Forced Expiratory Volume in 1 Second (FEV1) (NVA237 Versus Tiotropium)

  Spirometry was conducted according to internationally accepted standards. Trough FEV1 referred to the mean of FEV1 at 23:15 hours and 23:45 hours after the morning dose of study drug. The baseline was defined as the average of FEV1 values taken in the clinic 45 min and 15 min prior to the first dose of randomized treatment at Visit 3. A mixed model was used and contained treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilators, and FEV1 post-inhalation of bronchodilators and stratification factors as covariates. A positive change from baseline indicates improvement.

  baseline, 12 weeks

Secondary Outcomes (6)

• Change From Baseline in Mean Trough FEV1 (Flu/Sal Versus NVA237/Tiotropium+Flu/Sal)

  baseline, 4 weeks, 8 weeks, 12 weeks

• Change From Baseline in Mean Trough FEV1

  baseline, 4 weeks, 8 weeks, 12 weeks

• Change From Baseline in Total Score of the St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) After 12 Weeks of Treatment

  12 weeks

• Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Use

  baseline, 12 weeks

• Mean Percentage of Nights With 'no Nighttime Awakenings'

  12 weeks

Study Arms (3)

NVA237 + Fluticasone/Salmeterol (Flu/Sal)

EXPERIMENTAL

NVA237 50 µg once daily (NVA237 + Tiotropium placebo + Flu/Sal). NVA237 50 μg o.d., delivered via single-dose dry-powder inhaler (SDDPI) o.d. plus Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.

Drug: NVA237 50µg once daily; Drug: Flu/Sal; Drug: NVA237 placebo + Tiotropium placebo.

Tiotropium + Flu/Sal

ACTIVE COMPARATOR

Tiotropium 18µg once daily (NVA237 placebo + Tiotropium + Flu/Sal). Tiotropium 18 μg o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.

Drug: Tiotropium 18µg once daily; Drug: Flu/Sal; Drug: NVA237 placebo + Tiotropium placebo.

Flu/Sal

PLACEBO COMPARATOR

Placebo (NVA237 placebo + Tiotropium placebo + Flu/Sal). Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.

Drug: Flu/Sal; Drug: NVA237 placebo + Tiotropium placebo.

Interventions

NVA237 50µg once daily DRUG

NVA237 50 μg o.d., delivered via single-dose dry-powder inhaler (SDDPI)

NVA237 + Fluticasone/Salmeterol (Flu/Sal)

Tiotropium 18µg once daily DRUG

Tiotropium 18 μg o.d. delivered via a proprietary inhalation device

Tiotropium + Flu/Sal

Flu/Sal DRUG

Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device

Flu/Sal; NVA237 + Fluticasone/Salmeterol (Flu/Sal); Tiotropium + Flu/Sal

NVA237 placebo + Tiotropium placebo. DRUG

Tiotropium 18 μg o.d. delivered via a proprietary inhalation device

Flu/Sal; NVA237 + Fluticasone/Salmeterol (Flu/Sal); Tiotropium + Flu/Sal

Eligibility Criteria

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

You may qualify if:

• Patients with Moderate to Severe COPD (Stage II or Stage III) according to the GOLD 2010 guideline
• Current or ex-smokers who have a smoking history of at least 10 pack years
• Qualifying FEV1 at Visit 2 (day -7)

You may not qualify if:

• Patients with a history of asthma or a history of high blood eosinophil count (\>600/mm³)
• Patients with concomitant pulmonary disease
• Patients with lung lobectomy or lung volume reduction or lung transplantation
• Patients with α-1 antitrypsin deficiency
• Patients who have had live attenuated vaccinations within 30 days prior to screening visit or during run-in period

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (71)

Novartis Investigative Site

Baulkham Hills, New South Wales, 2153, Australia

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Novartis Investigative Site

Brookvale, New South Wales, 2100, Australia

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Castle Hill, New South Wales, 2067, Australia

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Dapto, New South Wales, Australia

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Darlinghurst, New South Wales, 2010, Australia

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Ermington, New South Wales, Australia

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Gosford, New South Wales, 2250, Australia

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Hinchinbrook, New South Wales, 2168, Australia

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Kingswood, New South Wales, 2747, Australia

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Sydney, New South Wales, 2089, Australia

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Arundel, Queensland, 4214, Australia

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Aspley, Queensland, 4034, Australia

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Beenleigh, Queensland, 4207, Australia

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Browns Plains, Queensland, 4118, Australia

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Chemside, Queensland, 4032, Australia

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Deception Bay, Queensland, 4508, Australia

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Everton Plaza, Queensland, 4053, Australia

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Holland Park, Queensland, 4121, Australia

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Jimboomba, Queensland, 4032, Australia

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Kedron, Queensland, Australia

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Novartis Investigative Site

Kenmore, Queensland, 4069, Australia

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Kippa-Ring, Queensland, 4021, Australia

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Logan Central, Queensland, 4114, Australia

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Loganholme, Queensland, 4129, Australia

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Mermaid Beach, Queensland, 4218, Australia

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Morayfield, Queensland, 4506, Australia

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Nerang, Queensland, 4211, Australia

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Woolloongabba, Queensland, 4102, Australia

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Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

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Daw Park, South Australia, 5041, Australia

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Glenelg East, South Australia, 5045, Australia

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Golden Grove, South Australia, 5125, Australia

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Hamley Bridge, South Australia, 5401, Australia

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Kensington Gardens, South Australia, 5065, Australia

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Prospect, South Australia, 5082, Australia

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Dandenong, Victoria, Australia

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Lalor, Victoria, 3075, Australia

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Malvern, Victoria, 3144, Australia

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Melbourne, Victoria, Australia

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Noble Park, Victoria, 3174, Australia

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Novartis Investigative Site

Oakleigh East, Victoria, 3166, Australia

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Preston, Victoria, Australia

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Novartis Investigative Site

Rosebud, Victoria, 3063, Australia

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Bicton, Western Australia, Australia

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East Fremantle, Western Australia, 6158, Australia

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East Victoria Park, Western Australia, 6101, Australia

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Fremantle, Western Australia, 6160, Australia

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Mirrabooka, Western Australia, 6061, Australia

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Morley, Western Australia, 6062, Australia

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Nedlands, Western Australia, 6009, Australia

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Noranda, Western Australia, Australia

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Novartis Investigative Site

Perth, Western Australia, 6000, Australia

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Novartis Investigative Site

Perth, Western Australia, 6069, Australia

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Perth, Western Australia, Australia

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Novartis Investigative Site

Pinjarra, Western Australia, Australia

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Novartis Investigative Site

Spearwood, Western Australia, 6163, Australia

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Novartis Investigative Site

Woodvale, Western Australia, 6026, Australia

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Novartis Investigative Site

Yokine, Western Australia, 6060, Australia

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Novartis Investigative Site

Auckland, New Zealand, 1051, New Zealand

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Novartis Investigative Site

Auckland, New Zealand, New Zealand

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Novartis Investigative Site

Christchurch, New Zealand, New Zealand

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Novartis Investigative Site

Hamilton, New Zealand, 3240, New Zealand

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Novartis Investigative Site

Tauranga, New Zealand, 3143, New Zealand

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Novartis Investigative Site

Tauranga, New Zealand, New Zealand

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Novartis Investigative Site

Tauranga, Tauranga, New Zealand

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Novartis Investigative Site

Wellington, Wellington Region, New Zealand

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Novartis Investigative Site

Auckland, New Zealand

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Novartis Investigative Site

Christchurch, New Zealand

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Novartis Investigative Site

Dunedin, New Zealand

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Novartis Investigative Site

Grafton, Auckland, 1010, New Zealand

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Novartis Investigative Site

Wellington, 6021, New Zealand

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Related Publications (1)

• Frith PA, Thompson PJ, Ratnavadivel R, Chang CL, Bremner P, Day P, Frenzel C, Kurstjens N; Glisten Study Group. Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study, a randomised controlled trial. Thorax. 2015 Jun;70(6):519-27. doi: 10.1136/thoraxjnl-2014-206670. Epub 2015 Apr 3.

  PMID: 25841237 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Glycopyrrolate; Tiotropium Bromide

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; Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

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 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2012
• First Posted: January 20, 2012
• Study Start: April 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: January 5, 2015
• Results First Posted: January 5, 2015

Record last verified: 2014-12

Locations

AU (58); NZ (13)