Chronic Obstructive Pulmonary DiseasePhase 3NCT03137992

Clinical Endpoint Bioequivalence Study of Test and Reference Inhalation Products in Patients With COPD With Device Robustness

A Phase 3 study testing Test Product (tiotropium bromide inhalation powder) and Reference Product (Spiriva®) in people with Chronic Obstructive Pulmonary Disease, run by Lupin, Inc. at 34 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to show bioequivalence of test product to reference product based on baseline-adjusted forced expiratory volume in one second (FEV1). Read more about this study

Who is it for?: Ages 40 years and older
Conditions the study is for: Chronic Obstructive Pulmonary Disease
What is being tested?: Test Product (tiotropium bromide inhalation powder) and Reference Product (Spiriva®)
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 377 participants
Where: 34 sitesUnited States
Study dates: 21 Nov 2017to 30 Apr 2018
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male and non-pregnant female subjects (40 years of age and older).
Patients with diagnosis of COPD according to the GOLD guidelines.
Post-bronchodilator FEV1 <80% of the predicted value at the screening visit.
Post-bronchodilator FEV1/FVC ratio ≤0.70 at the screening visit.
Current or former smokers (e.g., with history of = 10 pack-years).
Written informed consent.

Who cannot join

Known respiratory disorder other than COPD including, but not limited to the following: alpha-1 antitrypsin deficiency, cystic fibrosis, significant asthma, active bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, pulmonary edema, or interstitial lung disease.
History of allergy or hypersensitivity to anticholinergic/muscarinic receptor antagonist agents, beta-2 adrenergic agonists, lactose/milk proteins, or known hypersensitivity to any of the proposed ingredients or components of the delivery system.
Hospitalization for COPD or pneumonia within 12 weeks prior to the screening visit.
Treatment for COPD exacerbation within 12 weeks prior to the screening visit.
Viral or bacterial upper or lower respiratory tract infection, sinusitis, sinus infection, rhinitis, pharyngitis, middle ear infection, urinary tract infection, or illness within 6 weeks prior to the screening visit.
Abnormal and significant ECG finding prior to the screening, during the run-in and treatment periods.

Trial locations and contacts

34 sites in 1 country.

City, postcode or hospital

34 sites in 1 country

United States34 sites

Investigational Research Center Site #1017
Andalusia, Alabama, 36420
Investigational Research Center Site #1026
Clearwater, Florida, 33756
Investigational Research Center Site #1019
Clearwater, Florida, 33765
Investigational Research Center Site #1035
Clearwater, Florida, 33765
Investigational Research Center Site #1016
Colorado Springs, Colorado, 80907
Investigational Research Center Site #1037
Columbus, Ohio, 43215
Investigational Research Center Site #1015
Easley, South Carolina, 29640
Investigational Research Center Site #1018
Edmond, Oklahoma, 73034
Investigational Research Center Site #1013
El Paso, Texas, 79903
Investigational Research Center Site #1011
Fridley, Minnesota, 55432
Investigational Research Center Site #1012
Gaffney, South Carolina, 29340
Investigational Research Center Site #1008
Glendale, Arizona, 85306
Investigational Research Center Site #1003
Jasper, Alabama, 35501
Investigational Research Center Site #1004
Knoxville, Tennessee, 37909
Investigational Research Center Site #1007
Las Vegas, Nevada, 89119
Investigational Research Center Site #1034
Los Angeles, California, 90025
Investigational Research Center Site #1002
McKinney, Texas, 75069
Investigational Research Center Site #1005
Medford, Oregon, 97504
Investigational Research Center Site #1030
New Braunfels, Texas, 78130
Investigational Research Center Site #1031
Newport News, Virginia, 23606
Investigational Research Center Site #1001
North Dartmouth, Massachusetts, 02747
Investigational Research Center Site #1009
Oklahoma City, Oklahoma, 73103
Investigational Research Center Site #1036
Orlando, Florida, 32825
Investigational Research Center Site #1006
Portland, Oregon, 97202
Investigational Research Center Site #1032
Raleigh, North Carolina, 27607
Investigational Research Center Site #1028
Riverside, California, 92506
Investigational Research Center Site #1023
Rock Hill, South Carolina, 29732
Investigational Research Center Site #1024
Seneca, South Carolina, 29678
Investigational Research Center Site #1020
Spartanburg, South Carolina, 29303
Investigational Research Center Site #1025
Spartanburg, South Carolina, 29303
Investigational Research Center Site #1029
St Louis, Missouri, 63141
Investigational Research Center Site #1033
Tulsa, Oklahoma, 74136
Investigational Research Center Site #1027
Union, South Carolina, 29379
Investigational Research Center Site #1010
Westminster, California, 92683

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About this study

Official title: A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Crossover, Multicenter Clinical Study to Assess the Efficacy and Safety of Once Daily Administration of Lupin Tiotropium Bromide Inhalation Powder Compared to SPIRIVA® HANDIHALER® and Placebo in Patients With COPD Including a 12-Week Open Label Extension to Assess Inhaler Robustness

The purpose of this study is to show bioequivalence of test product to reference product based on baseline-adjusted forced expiratory volume in one second (FEV1).

Conditions: Chronic Obstructive Pulmonary Disease
Being tested: Placebo, Test Product (tiotropium bromide inhalation powder), Reference Product (Spiriva®)
Keywords: COPD
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Single dose of placebo inhalation powder administered by test and reference dry powder inhalers.
Test Product (tiotropium bromide inhalation powder)Drug
Double-Blind: Single dose of test product 18 mcg of test product Open-Label: once daily administration of test product (tiotropium bromide inhalation powder) 18 mcg administered by test dry powder inhaler.
Reference Product (Spiriva®)Drug
Reference product (Spiriva®) 18 mcg.

Study groups in NCT03137992
Study group	Role	What they receive
Test Product (tiotropium bromide inhalation powder)	Experimental	Once daily administration of test product (tiotropium bromide inhalation powder), 18 mcg for open-label extension (device robustness). Receives: Drug: Test Product (tiotropium bromide inhalation powder)
Reference Product (Spiriva®)	Active comparator	Single dose of reference product (Spiriva®) 18 mcg Receives: Drug: Reference Product (Spiriva®)
Placebo	Placebo comparator	Single dose of placebo inhalation powder Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Baseline Adjusted Mean Change in FEV1 AUC0-24h Post Dose
To show clinical bioequivalence in the efficacy of the test product as a single dose versus reference product based on the baseline adjusted mean change in forced expiratory volume in the first second (FEV1) area under the curve from time zero to 24 hours post dose (AUC0-24h) on day 1 zero to 24 hours post-dose (AUC0-24h). Baseline was defined as the average of the FEV1 values recorded at approximately 30 minutes and 15 minutes before dosing with study medication.
Measured: 0-24 hours after dosing on Day 1 of visits 2-4 over a period of approximately 6 weeks
Difference in Baseline Adjusted FEV1 AUC0-24h for Comparison of Lupin Tiotropium Bromide Inhalation Powder (Test) and Spiriva (Reference) to Placebo
This measure is to demonstrate that test product as a single dose and reference product are superior to placebo based on the baseline adjusted mean change in forced expiratory volume in the first second (FEV1) area under the curve from time zero to 24 hours post dose (AUC0-24h) on day 1 zero to 24 hours post-dose (AUC0-24h). Baseline was defined as the average of the FEV1 values recorded at approximately 30 minutes and 15 minutes before dosing with study medication.
Measured: 0-24 hours after dosing on Day 1 of visits 2-4 over a period of approximately 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Nov 201730 Apr 2018

First posted3 May 2017
Study start21 Nov 2017
Primary completion31 Jan 2018
Study completion30 Apr 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: Double-blind, double-dummy, placebo controlled
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 377 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03137992
Sponsor's protocol ID: TB-DPI-301
Status last verified: Mar 2021
First submitted: 30 Apr 2017
Last updated: 5 Apr 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Chronic Obstructive Pulmonary Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Crossover, Multicenter Clinical Study to Assess the Efficacy and Safety of Once Daily Administration of Lupin Tiotropium Bromide Inhalation Powder Compared to SPIRIVA® HANDIHALER® and Placebo in Patients With COPD Including a 12-Week Open Label Extension to Assess Inhaler Robustness
ClinicalTrials.gov ID: NCT03137992
Acronym / sponsor ID: TB-DPI-301
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 377 participants (actual)
Lead sponsor: Lupin, Inc.Industry (pharma, biotech, devices)
Study start: 21 Nov 2017 (actual)
Primary completion: 31 Jan 2018 (actual)
Study completion: 30 Apr 2018 (actual)
First posted: 3 May 2017 (actual)
Results: Posted 5 Apr 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to show bioequivalence of test product to reference product based on baseline-adjusted forced expiratory volume in one second (FEV1).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 3
Model description: Double-blind, double-dummy, placebo controlled

Arm	Type	Receives
Test Product (tiotropium bromide inhalation powder)	Experimental	Drug: Test Product (tiotropium bromide inhalation powder)Once daily administration of test product (tiotropium bromide inhalation powder), 18 mcg for open-label extension (device robustness).
Reference Product (Spiriva®)	Active comparator	Drug: Reference Product (Spiriva®)Single dose of reference product (Spiriva®) 18 mcg
Placebo	Placebo comparator	Drug: PlaceboSingle dose of placebo inhalation powder

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Male and non-pregnant female subjects (40 years of age and older).
Patients with diagnosis of COPD according to the GOLD guidelines.
Post-bronchodilator FEV1 <80% of the predicted value at the screening visit.
Post-bronchodilator FEV1/FVC ratio ≤0.70 at the screening visit.
Current or former smokers (e.g., with history of = 10 pack-years).

Key exclusion criteria (6 listed)

Known respiratory disorder other than COPD including, but not limited to the following: alpha-1 antitrypsin deficiency, cystic fibrosis, significant asthma, active bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, pulmonary edema, or interstitial lung disease.
History of allergy or hypersensitivity to anticholinergic/muscarinic receptor antagonist agents, beta-2 adrenergic agonists, lactose/milk proteins, or known hypersensitivity to any of the proposed ingredients or components of the delivery system.
Hospitalization for COPD or pneumonia within 12 weeks prior to the screening visit.
Treatment for COPD exacerbation within 12 weeks prior to the screening visit.
Viral or bacterial upper or lower respiratory tract infection, sinusitis, sinus infection, rhinitis, pharyngitis, middle ear infection, urinary tract infection, or illness within 6 weeks prior to the screening visit.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboSingle dose of placebo inhalation powder administered by test and reference dry powder inhalers.	Drug	Placebo
Test Product (tiotropium bromide inhalation powder)Double-Blind: Single dose of test product 18 mcg of test product Open-Label: once daily administration of test product (tiotropium bromide inhalation powder) 18 mcg administered by test dry powder inhaler.	Drug	Test Product (tiotropium bromide inhalation powder)
Reference Product (Spiriva®)Reference product (Spiriva®) 18 mcg.	Drug	Reference Product (Spiriva®)

Primary outcome

Baseline Adjusted Mean Change in FEV1 AUC0-24h Post Dose
Time frame: 0-24 hours after dosing on Day 1 of visits 2-4 over a period of approximately 6 weeks
To show clinical bioequivalence in the efficacy of the test product as a single dose versus reference product based on the baseline adjusted mean change in forced expiratory volume in the first second (FEV1) area under the curve from time zero to 24 hours post dose (AUC0-24h) on day 1 zero to 24 hours post-dose (AUC0-24h). Baseline was defined as the average of the FEV1 values recorded at approximately 30 minutes and 15 minutes before dosing with study medication.
Difference in Baseline Adjusted FEV1 AUC0-24h for Comparison of Lupin Tiotropium Bromide Inhalation Powder (Test) and Spiriva (Reference) to Placebo
Time frame: 0-24 hours after dosing on Day 1 of visits 2-4 over a period of approximately 6 weeks
This measure is to demonstrate that test product as a single dose and reference product are superior to placebo based on the baseline adjusted mean change in forced expiratory volume in the first second (FEV1) area under the curve from time zero to 24 hours post dose (AUC0-24h) on day 1 zero to 24 hours post-dose (AUC0-24h). Baseline was defined as the average of the FEV1 values recorded at approximately 30 minutes and 15 minutes before dosing with study medication.

Results and safety

Results posted to the registry on 5 Apr 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sequence A (T-R-P)	62	62
Sequence B (R-P-T)	63	63
Sequence C (P-T-R)	63	63
Sequence D (P-R-T)	63	63
Sequence E (T-P-R)	62	62
Sequence F (R-T-P)	61	61

Primary outcome: Baseline Adjusted Mean Change in FEV1 AUC0-24h Post Dose

Time frame: 0-24 hours after dosing on Day 1 of visits 2-4 over a period of approximately 6 weeks. Least squares mean (Standard Error). Unit: L*hour

Measure	Test Product (Tiotropium Bromide Inhalation Powder) n = 291	Reference Product (Spiriva®) n = 291
Value	2.5644 (0.323)	2.7370 (0.322)

Test Product (Tiotropium Bromide Inhalation Powder) vs Reference Product (Spiriva®): Least Squared Mean Ratio: 0.9369 (90% CI 0.834 to 1.047)

Population analysed: Per-Protocol population

Primary outcome: Difference in Baseline Adjusted FEV1 AUC0-24h for Comparison of Lupin Tiotropium Bromide Inhalation Powder (Test) and Spiriva (Reference) to Placebo

Time frame: 0-24 hours after dosing on Day 1 of visits 2-4 over a period of approximately 6 weeks. Least squares mean (Standard Error). Unit: L*hour

Measure	Test Product (Tiotropium Bromide Inhalation Powder) n = 372	Reference Product (Spiriva®) n = 372	Placebo n = 372
Value	2.90 (0.197)	3.03 (0.196)	-0.40 (0.199)

Test Product (Tiotropium Bromide Inhalation Powder) vs Placebo: Least Squared Mean Difference: 3.29 (95% CI 2.9386 to 3.646), p <0.001, Mixed Models Analysis
Reference Product (Spiriva®) vs Placebo: Least Squared Mean Difference: 3.43 (95% CI 3.0718 to 3.7797), p <0.001, Mixed Models Analysis

Population analysed: Intention-To-Treat population

Adverse events

Time frame: All AEs/SAEs were assessed through study completion, an average of 14 weeks for participants enrolled in only part 1 of the study and 26 weeks for participants enrolled in part 1 and part 2 of the study. AEs were recorded starting after the patient signed the informed consent form and assessed at each visit.. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Test Product (Lupin Tiotropium Bromide Inhalation Powder)	0 of 337 (0%)	0 of 337 (0%)	0 of 337
Reference Product (Spiriva®)	0 of 343 (0%)	0 of 343 (0%)	0 of 343
Placebo	0 of 329 (0%)	0 of 329 (0%)	0 of 329

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Chronic Obstructive Pulmonary Disease

Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
COPD, Smoking
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

34 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Baseline Adjusted Mean Change in FEV1 AUC0-24h Post Dose (time frame: 0-24 hours after dosing on Day 1 of visits 2-4 over a period of approximately 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03137992.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2021.