Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD)Phase 2NCT03118765

Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Inhalation Solution in Patients With Chronic Obstructive Pulmonary Disease (COPD)

A Phase 2 study testing GSP304 (tiotropium bromide) Inhalation Solution and Spiriva® Respimat® inhalation spray in people with Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD), run by Glenmark Specialty S.A. at 25 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

Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Inhalation Solution in Patients With Chronic Obstructive Pulmonary Disease (COPD). Read more about this study

Who is it for?: Ages 40 to 85 years
Conditions the study is for: Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD)
What is being tested?: GSP304 (tiotropium bromide) Inhalation Solution and Spiriva® Respimat® inhalation spray
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 155 participants
Where: 25 sitesUnited States
Study dates: 24 Mar 2017to 31 Jul 2017
Phase: Phase 2
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 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male and female subjects ≥40 years and ≤85 years of age at the time of consent.
Subject must have a primary diagnosis of mild or moderate COPD defined as post-bronchodilator FEV1/FVC ratio of <70% and FEV1 of ≥50% of predicted normal value as per the NHANES III predicted normal values at screening.
Willing to stop all other COPD medications or other medications which will interfere with the study results for the entire duration of the study, except albuterol/salbutamol as needed.
Current or ex-smoker with ≥10 pack-year smoking history.

Who cannot join

Subjects with a chest x-ray/CT scan that suggests a diagnosis other than COPD (eg, pneumonia, other infection, atelectasis, or pneumothorax or other active/ongoing pulmonary conditions) and taken within 6 months prior to study start. If there is no chest x-ray or CT scan taken within 6 months prior to study start, or if recent results are unavailable for review, a chest x-ray must be performed.
Use of oral/parenteral corticosteroids or antibiotics for COPD within 6 weeks or depot corticosteroids within 3 months prior to screening or subject has had a change in dose or type of any medications for COPD within 14 days before screening.
Hospitalization for COPD exacerbation or pneumonia within 3 months prior to screening.
Subjects with a history of asthma, with the exception of outgrown childhood asthma, defined as transient wheezers outgrown by 5 years of age.
Subject has a known history of alpha 1 antitrypsin deficiency-related emphysema.
Subject requires nocturnal oxygen or continuous supplemental oxygen therapy.

Show all 10Show fewer

Subject with history of a positive result for HBsAg or HCV antibody.
Subject is known to be seropositive for human immunodeficiency virus.
Female subject is pregnant or lactating.
Subject has a history of allergic reaction to the anti-cholinergic or any components of the study medications.

Trial locations and contacts

25 sites in 1 country.

City, postcode or hospital

25 sites in 1 country

United States25 sites

Glenmark Investigational Site 23
Andalusia, Alabama, 36420
Glenmark Investigational Site 9
Charlotte, North Carolina, 28207
Glenmark Investigational Site 5
Columbus, Ohio, 43213
Glenmark Investigational Site 22
Columbus, Ohio, 43215
Glenmark Investigational Site 8
Dublin, Ohio, 43016
Glenmark Investigational Site 3
Easley, South Carolina, 29640
Glenmark Investigational Site 19
Edgewater, Florida, 32132
Glenmark Investigational Site 17
Fullerton, California, 92835
Glenmark Investigational Site 2
Greenville, South Carolina, 29615
Glenmark Investigational Site 4
Greenville, South Carolina, 29615
Glenmark Investigational Site 18
Las Vegas, Nevada, 89119
Glenmark Investigational Site 11
Medford, Oregon, 97504-9741
Glenmark Investigational Site 24
Miami, Florida, 33144
Glenmark Investigational Site 16
Miami, Florida, 33186
Glenmark Investigational Site 10
Miami Lakes, Florida, 33016
Glenmark Investigational Site 6
Orlando, Florida, 32825
Glenmark Investigational Site 20
Ormond Beach, Florida, 32124
Glenmark Investigational Site 12
Phoenix, Arizona, 85006
Glenmark Investigational Site 1
Rock Hill, South Carolina, 29732
Glenmark Investigational Site 15
Spartanburg, South Carolina, 29303
Glenmark Investigational Site 7
Spartanburg, South Carolina, 29303
Glenmark Investigational Site 14
Tempe, Arizona, 85283
Glenmark Investigational Site 25
Tomball, Texas, 77375
Glenmark Investigational Site 21
Vero Beach, Florida, 32960
Glenmark Investigational Site 13
Winter Park, Florida, 32789

Other trials in United States

About this study

Official title: A Dose Ranging, Parallel Group, Active (Spiriva® Respimat®) And Placebo Controlled Study To Assess Relative Bioavailability, Pharmacodynamics And Safety Of Three Doses Of Tiotropium Bromide Inhalation Solution In Subjects With Mild To Moderate Chronic Obstructive Pulmonary Disease

Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Inhalation Solution in Patients With Chronic Obstructive Pulmonary Disease (COPD).

Conditions: Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD)
Being tested: GSP304 (tiotropium bromide) Inhalation Solution, GSP304 Placebo Inhalation Solution, Spiriva® Respimat® inhalation spray

What participants receive

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

GSP304 (tiotropium bromide) Inhalation SolutionDrug
Once daily (QD) oral inhalation using a nebulizer
GSP304 Placebo Inhalation SolutionDrug
Once daily (QD) oral inhalation using a nebulizer
Spiriva® Respimat® inhalation sprayDrug
Once daily (QD) oral inhalation

Study groups in NCT03118765
Study group	Role	What they receive
Test Treatment T1: GSP304 Inhalation Solution	Experimental	Not described Receives: Drug: GSP304 (tiotropium bromide) Inhalation Solution
Test Treatment T2: GSP304 Inhalation Solution	Experimental	Not described Receives: Drug: GSP304 (tiotropium bromide) Inhalation Solution
Test Treatment T3: GSP304 Inhalation Solution	Experimental	Not described Receives: Drug: GSP304 (tiotropium bromide) Inhalation Solution
Test Treatment T4: GSP304 Placebo Inhalation Solution	Placebo comparator	Not described Receives: Drug: GSP304 Placebo Inhalation Solution
Test Treatment T5: Spiriva® Respimat® inhalation spray	Active comparator	Not described Receives: Drug: Spiriva® Respimat® inhalation spray

What is being measured

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

Relative Bioavailability of Tiotropium With GSP304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on CmaxSS
The PK endpoint in plasma to assess the relative bioavailability was peak concentrations of tiotropium during the dosing interval at steady-state (CmaxSS)
Measured: Plasma concentrations on day 21 according to the below schedule: Pre-dose (0 hour), and at 2, 4, 6, 10, 15, 30, and 45, 60, 75, and 90 minutes post-dose, as well as 2, 4, 6, 8, 12, 16, 20 and 24 hours post-dose.
Relative Bioavailability of Tiotropium With GSP 304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on AUC0-tauSS
The PK endpoint in plasma to assess the relative bioavailability was area under the plasma concentration-time curve of tiotropium over the dosing interval at steady state (AUC0-tauSS)
Measured: Plasma concentrations on day 21 according to the below schedule: Pre-dose (0 hour), and at 2, 4, 6, 10, 15, 30, and 45, 60, 75, and 90 minutes post-dose, as well as 2, 4, 6, 8, 12, 16, 20 and 24 hours post-dose.
Change From Baseline (Day 1) in Trough FEV1 at 24 Hours After the Last Dose of Treatment on Day 21 in Comparison to Placebo.
Change from baseline (Day 1) at Day 21 (Week 3) in trough FEV1 response at approximately 24 hours after the last dose (average of 23 hours 15 minutes and 23 hours 45 minutes postdose measurements), in comparison with placebo.
Measured: 21 days (Pre- dose trough FEV1 is mean FEV1 at -45 mins and -15 mins pre-morning dose at Day 1. Trough FEV1 is mean FEV1 obtained 23 hrs 15 mins and 23 hrs 45 mins post-morning dose of day 21).

Secondary outcomes (17)

Amount (Aetau) (Cumulative Amount of Unchanged Drug Excreted Into the Urine Over the Dosing Interval) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 1
Descriptive statistics for tiotropium urine PK parameter - Amount (Aetau) of tiotropium excreted in urine over the dosing interval on Day 1
Measured: Day 1
Amount (Aetau) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21
Descriptive statistics for tiotropium urine PK parameter - Amount (Aetau) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21
Measured: Day 21
Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 1
Descriptive statistics for tiotropium urine PK parameter - Fraction of dose (Fe) of tiotropium excreted in urine over the dosing interval on Day 1
Measured: Day 1
Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21
Descriptive statistics for tiotropium urine PK parameter-Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21
Measured: Day 21
Peak Concentrations During the Dosing Interval (Cmax) on Day 1
Descriptive statistics for tiotropium plasma PK parameters - (Cmax) on Day 1
Measured: Day 1
Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) on Day 1
Descriptive statistics for tiotropium plasma PK parameter - Area under the plasma concentration-time curve over the dosing interval (AUC0-tau) on Day 1
Measured: Day 1
Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 1
Descriptive statistics for tiotropium plasma PK parameter - Time of peak drug concentration over the dosing interval (tmax) on Day 1
Measured: Day 1
Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 21
Descriptive statistics for tiotropium plasma PK parameter - Time of peak drug concentration over the dosing interval (tmax) on Day 21
Measured: Day 21
Average Concentration During a Dosing Interval at Steady State (CavSS) on Day 21
Descriptive statistics for tiotropium plasma PK parameter - Average concentration during a dosing interval at steady state (CavSS) on day 21
Measured: Day 21
Accumulation Ratio Rac(Auc)
Descriptive statistics for tiotropium plasma PK parameter-Accumulation ratio Rac(auc). Rac(auc) was calculated as AUC0-tauSS/AUC0-tau.
Measured: Day 21
Accumulation Ratio Rac(Cmax)
Descriptive statistics for tiotropium plasma PK parameter-Accumulation ratio Rac(cmax). Rac(Cmax) was calculated as CmaxSS/Cmax.
Measured: Day 21
Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 1
The least square mean change from baseline to peak FEV1 within 12 hours postdose on Day 1. Change from baseline in peak FEV1 within 12 hours postdose on Day 1 was derived from the serial readings taken through 12 hours postdose and calculating the change from baseline.
Measured: Day 1 (Pre-dose FEV1 at -45 mins and 15 mins prior to dosing on Day 1. On Day 1 FEV1 at post-dose at 5 mins ±3, 15 mins ±2, 30 mins ±5, 60 mins, 90 mins, and 2 hours; and post-dose at 4, 6, 8, 10, 12 hours after the morning dose).
Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 21
The least square mean change from baseline to peak FEV1 within 12 hours postdose on Day 21. Change from baseline in peak FEV1 within 12 hours postdose on Day 21 was derived from the serial readings taken through 12 hours postdose and calculating the change from baseline.
Measured: Day 21(Pre-dose FEV1 at -45 mins and 15 mins prior to dosing on Day 21. On Day 21, FEV1 at post-dose at 5 mins ±3, 15 mins ±2, 30 mins ±5, 60 mins, 90 mins, and 2 hours; and post-dose at 4, 6, 8, 10, 12 hours after the morning dose).
Change From Baseline in Forced Vital Capacity (FVC) on Day 1
Least Square Mean change from baseline in forced vital capacity (FVC) to end of Day 1.
Measured: Day 1 (Pre-dose FVC at -45 mins and 15 mins prior to dosing on Day 1. Postdose timing were relative to the end of dosing.The window for 1 hour spirometry and thereafter was ±5 minutes).
Change From Baseline in Forced Vital Capacity (FVC) on Day 21
Least Square Mean change from baseline in forced vital capacity (FVC) to end of Day 21
Measured: Day 21 (Pre-dose FVC at -45 mins and 15 mins prior to dosing on Day 21. Postdose timing were relative to the end of dosing. The window for 1 hour spirometry and thereafter was ±5 minutes).
Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 1
Least Square Mean (SE) change from baseline in time-normalized area under the curve for FEV1 measured over 12 hours on Day 1.
Measured: Day 1 (Pre-dose FEV1 at -45 mins and 15 mins prior to dosing on Day 1. On Day 1 FEV1 at post-dose at 5 mins ±3, 15 mins ±2, 30 mins ±5, 60 mins, 90 mins, and 2 hours; and post-dose at 4, 6, 8, 10, 12 hours after the morning dose).
Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 21
Least Square Mean (SE) change from baseline in time-normalized area under the curve for FEV1 Measured Over 12 Hours on Day 21.
Measured: Day 21(Pre-dose FEV1 at -45 mins and 15 mins prior to dosing on Day 21. On Day 21, FEV1 at post-dose at 5 mins ±3, 15 mins ±2, 30 mins ±5, 60 mins, 90 mins, and 2 hours; and post-dose at 4, 6, 8, 10, 12 hours after the morning dose).

Timeline

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

24 Mar 201731 Jul 2017

First posted18 Apr 2017
Study start24 Mar 2017
Primary completion31 Jul 2017
Study completion31 Jul 2017

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 Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD)Studies 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 155 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03118765
Sponsor's protocol ID: GSP304-201
Status last verified: Jul 2019
First submitted: 10 Apr 2017
Last updated: 1 Aug 2019
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?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Dose Ranging, Parallel Group, Active (Spiriva® Respimat®) And Placebo Controlled Study To Assess Relative Bioavailability, Pharmacodynamics And Safety Of Three Doses Of Tiotropium Bromide Inhalation Solution In Subjects With Mild To Moderate Chronic Obstructive Pulmonary Disease
ClinicalTrials.gov ID: NCT03118765
Acronym / sponsor ID: GSP304-201
Conditions: Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD)
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 155 participants (actual)
Lead sponsor: Glenmark Specialty S.A.Industry (pharma, biotech, devices)
Study start: 24 Mar 2017 (actual)
Primary completion: 31 Jul 2017 (actual)
Study completion: 31 Jul 2017 (actual)
First posted: 18 Apr 2017 (actual)
Results: Posted 1 Aug 2019

Clinical summary

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

Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Inhalation Solution in Patients With Chronic Obstructive Pulmonary Disease (COPD).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
Test Treatment T1: GSP304 Inhalation Solution	Experimental	Drug: GSP304 (tiotropium bromide) Inhalation Solution
Test Treatment T2: GSP304 Inhalation Solution	Experimental	Drug: GSP304 (tiotropium bromide) Inhalation Solution
Test Treatment T3: GSP304 Inhalation Solution	Experimental	Drug: GSP304 (tiotropium bromide) Inhalation Solution
Test Treatment T4: GSP304 Placebo Inhalation Solution	Placebo comparator	Drug: GSP304 Placebo Inhalation Solution
Test Treatment T5: Spiriva® Respimat® inhalation spray	Active comparator	Drug: Spiriva® Respimat® inhalation spray

Who may qualify

Ages: 40 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Male and female subjects ≥40 years and ≤85 years of age at the time of consent.
Subject must have a primary diagnosis of mild or moderate COPD defined as post-bronchodilator FEV1/FVC ratio of <70% and FEV1 of ≥50% of predicted normal value as per the NHANES III predicted normal values at screening.
Willing to stop all other COPD medications or other medications which will interfere with the study results for the entire duration of the study, except albuterol/salbutamol as needed.
Current or ex-smoker with ≥10 pack-year smoking history.

Key exclusion criteria (10 listed)

Subjects with a chest x-ray/CT scan that suggests a diagnosis other than COPD (eg, pneumonia, other infection, atelectasis, or pneumothorax or other active/ongoing pulmonary conditions) and taken within 6 months prior to study start. If there is no chest x-ray or CT scan taken within 6 months prior to study start, or if recent results are unavailable for review, a chest x-ray must be performed.
Use of oral/parenteral corticosteroids or antibiotics for COPD within 6 weeks or depot corticosteroids within 3 months prior to screening or subject has had a change in dose or type of any medications for COPD within 14 days before screening.
Hospitalization for COPD exacerbation or pneumonia within 3 months prior to screening.
Subjects with a history of asthma, with the exception of outgrown childhood asthma, defined as transient wheezers outgrown by 5 years of age.
Subject has a known history of alpha 1 antitrypsin deficiency-related emphysema.

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
GSP304 (tiotropium bromide) Inhalation SolutionOnce daily (QD) oral inhalation using a nebulizer	Drug	Test Treatment T1: GSP304 Inhalation Solution, Test Treatment T2: GSP304 Inhalation Solution, Test Treatment T3: GSP304 Inhalation Solution
GSP304 Placebo Inhalation SolutionOnce daily (QD) oral inhalation using a nebulizer	Drug	Test Treatment T4: GSP304 Placebo Inhalation Solution
Spiriva® Respimat® inhalation sprayOnce daily (QD) oral inhalation	Drug	Test Treatment T5: Spiriva® Respimat® inhalation spray

Primary outcome

Relative Bioavailability of Tiotropium With GSP304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on CmaxSS
Time frame: Plasma concentrations on day 21 according to the below schedule: Pre-dose (0 hour), and at 2, 4, 6, 10, 15, 30, and 45, 60, 75, and 90 minutes post-dose, as well as 2, 4, 6, 8, 12, 16, 20 and 24 hours post-dose.
The PK endpoint in plasma to assess the relative bioavailability was peak concentrations of tiotropium during the dosing interval at steady-state (CmaxSS)
Relative Bioavailability of Tiotropium With GSP 304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on AUC0-tauSS
Time frame: Plasma concentrations on day 21 according to the below schedule: Pre-dose (0 hour), and at 2, 4, 6, 10, 15, 30, and 45, 60, 75, and 90 minutes post-dose, as well as 2, 4, 6, 8, 12, 16, 20 and 24 hours post-dose.
The PK endpoint in plasma to assess the relative bioavailability was area under the plasma concentration-time curve of tiotropium over the dosing interval at steady state (AUC0-tauSS)
Change From Baseline (Day 1) in Trough FEV1 at 24 Hours After the Last Dose of Treatment on Day 21 in Comparison to Placebo.
Time frame: 21 days (Pre- dose trough FEV1 is mean FEV1 at -45 mins and -15 mins pre-morning dose at Day 1. Trough FEV1 is mean FEV1 obtained 23 hrs 15 mins and 23 hrs 45 mins post-morning dose of day 21).
Change from baseline (Day 1) at Day 21 (Week 3) in trough FEV1 response at approximately 24 hours after the last dose (average of 23 hours 15 minutes and 23 hours 45 minutes postdose measurements), in comparison with placebo.

17 secondary outcomes

Amount (Aetau) (Cumulative Amount of Unchanged Drug Excreted Into the Urine Over the Dosing Interval) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 1
Time frame: Day 1
Amount (Aetau) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21
Time frame: Day 21
Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 1
Time frame: Day 1
Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21
Time frame: Day 21
Peak Concentrations During the Dosing Interval (Cmax) on Day 1
Time frame: Day 1
Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) on Day 1
Time frame: Day 1
Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 1
Time frame: Day 1
Time of Peak Drug Concentration Over the Dosing Interval (Tmax) on Day 21
Time frame: Day 21
Average Concentration During a Dosing Interval at Steady State (CavSS) on Day 21
Time frame: Day 21
Accumulation Ratio Rac(Auc)
Time frame: Day 21
Accumulation Ratio Rac(Cmax)
Time frame: Day 21
Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 1
Time frame: Day 1 (Pre-dose FEV1 at -45 mins and 15 mins prior to dosing on Day 1. On Day 1 FEV1 at post-dose at 5 mins ±3, 15 mins ±2, 30 mins ±5, 60 mins, 90 mins, and 2 hours; and post-dose at 4, 6, 8, 10, 12 hours after the morning dose).
Change From Baseline in Peak FEV1 Within 12 Hours Post-dose on Day 21
Time frame: Day 21(Pre-dose FEV1 at -45 mins and 15 mins prior to dosing on Day 21. On Day 21, FEV1 at post-dose at 5 mins ±3, 15 mins ±2, 30 mins ±5, 60 mins, 90 mins, and 2 hours; and post-dose at 4, 6, 8, 10, 12 hours after the morning dose).
Change From Baseline in Forced Vital Capacity (FVC) on Day 1
Time frame: Day 1 (Pre-dose FVC at -45 mins and 15 mins prior to dosing on Day 1. Postdose timing were relative to the end of dosing.The window for 1 hour spirometry and thereafter was ±5 minutes).
Change From Baseline in Forced Vital Capacity (FVC) on Day 21
Time frame: Day 21 (Pre-dose FVC at -45 mins and 15 mins prior to dosing on Day 21. Postdose timing were relative to the end of dosing. The window for 1 hour spirometry and thereafter was ±5 minutes).
Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 1
Time frame: Day 1 (Pre-dose FEV1 at -45 mins and 15 mins prior to dosing on Day 1. On Day 1 FEV1 at post-dose at 5 mins ±3, 15 mins ±2, 30 mins ±5, 60 mins, 90 mins, and 2 hours; and post-dose at 4, 6, 8, 10, 12 hours after the morning dose).
Change From Baseline in Time-normalized Area Under the Curve for FEV1 Measured Over 12 Hours on Day 21
Time frame: Day 21(Pre-dose FEV1 at -45 mins and 15 mins prior to dosing on Day 21. On Day 21, FEV1 at post-dose at 5 mins ±3, 15 mins ±2, 30 mins ±5, 60 mins, 90 mins, and 2 hours; and post-dose at 4, 6, 8, 10, 12 hours after the morning dose).

Results and safety

Results posted to the registry on 1 Aug 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
GSP304 10 μg	30	26
GSP304 20 μg	32	30
GSP304 40 μg	31	26
Placebo	32	29
SPIRIVA RESPIMAT 5 μg	30	28

Primary outcome: Relative Bioavailability of Tiotropium With GSP304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on CmaxSS

Time frame: Plasma concentrations on day 21 according to the below schedule: Pre-dose (0 hour), and at 2, 4, 6, 10, 15, 30, and 45, 60, 75, and 90 minutes post-dose, as well as 2, 4, 6, 8, 12, 16, 20 and 24 hours post-dose.. Mean (Standard Error). Unit: pg/mL

Measure	GSP304 10 μg n = 26	GSP304 20 μg n = 30	GSP304 40 μg n = 26	SPIRIVA RESPIMAT 5 μg n = 26
Value	4.10 (1.152)	8.00 (1.140)	21.80 (1.152)	14.00 (1.152)

GSP304 10 μg vs SPIRIVA RESPIMAT 5 μg: LS mean ratio (%): 29.4 (90% CI 21.14 to 41.00)
GSP304 20 μg vs SPIRIVA RESPIMAT 5 μg: LS mean ratio (%): 57 (90% CI 41.37 to 78.46)
GSP304 40 μg vs SPIRIVA RESPIMAT 5 μg: LS mean ratio (%): 155.80 (90% CI 111.88 to 216.99)

Population analysed: The PK analysis set consisted of all subjects who were randomized, received at least 1 dose of study treatment, and had at least 1 quantifiable PK sample and did not have an exclusionary major protocol deviation.

Primary outcome: Relative Bioavailability of Tiotropium With GSP 304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on AUC0-tauSS

Measure	GSP304 10 μg n = 26	GSP304 20 μg n = 29	GSP304 40 μg n = 26	SPIRIVA RESPIMAT 5 μg n = 26
Value	22.90 (1.130)	49.10 (1.123)	122.00 (1.130)	57.70 (1.130)

GSP304 10 μg vs SPIRIVA RESPIMAT 5 μg: LS mean ratio (%): 39.70 (90% CI 29.79 to 52.87)
GSP304 20 μg vs SPIRIVA RESPIMAT 5 μg: LS mean ratio (%): 85.20 (90% CI 64.43 to 112.64)
GSP304 40 μg vs SPIRIVA RESPIMAT 5 μg: LS mean ratio (%): 211.50 (90% CI 158.80 to 281.80)

Primary outcome: Change From Baseline (Day 1) in Trough FEV1 at 24 Hours After the Last Dose of Treatment on Day 21 in Comparison to Placebo.

Time frame: 21 days (Pre- dose trough FEV1 is mean FEV1 at -45 mins and -15 mins pre-morning dose at Day 1. Trough FEV1 is mean FEV1 obtained 23 hrs 15 mins and 23 hrs 45 mins post-morning dose of day 21).. Mean (Standard Error). Unit: L

Measure	GSP304 10 μg n = 30	GSP304 20 μg n = 32	GSP304 40 μg n = 31	Placebo n = 32	SPIRIVA RESPIMAT 5 μg n = 30
Value	0.14 (0.04)	0.10 (0.04)	0.09 (0.04)	0.08 (0.04)	0.14 (0.04)

GSP304 10 μg vs Placebo: Mean Difference (Final Values): 0.06 (95% CI -0.04 to 0.17), p = 0.228, MMRM
GSP304 20 μg vs Placebo: Mean Difference (Net): 0.02 (95% CI -0.08 to 0.13), p = 0.655, MMRM
GSP304 40 μg vs Placebo: Mean Difference (Final Values): 0.01 (95% CI -0.10 to 0.11), p = 0.894, MMRM

17 secondary outcomes are reported in the full results.

Adverse events

Time frame: The AEs and SAEs were collected from the time of signing the informed consent form until the end of study and the follow-up contact which was approximately 9 weeks i.e., upto 2 weeks of screening, 2 weeks of run-in period, 3 weeks of treatment and follow up of 2 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
GSP304 10 μg	0 of 30 (0%)	3 of 30 (10%)	0 of 30
GSP304 20 μg	0 of 32 (0%)	6 of 32 (18.8%)	0 of 32
GSP304 40 μg	0 of 31 (0%)	5 of 31 (16.1%)	0 of 31
Placebo	0 of 33 (0%)	4 of 33 (12.1%)	0 of 33
SPIRIVA RESPIMAT 5 μg	0 of 30 (0%)	6 of 30 (20%)	0 of 30

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Cynthia Caracta, MD FCCP study director

Glenmark Pharmaceuticals S.A.

25 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 4 inclusion and 10 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 1 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 1 Aug 2019). 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?

Relative Bioavailability of Tiotropium With GSP304 in Comparison to SPIRIVA RESPIMAT 5 μg Based on CmaxSS (time frame: Plasma concentrations on day 21 according to the below schedule: Pre-dose (0 hour), and at 2, 4, 6, 10, 15, 30, and 45, 60, 75, and 90 minutes post-dose, as well as 2, 4, 6, 8, 12, 16, 20 and 24 hours post-dose.). The study lists 3 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 NCT03118765.

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 1 Aug 2019.