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

NCT03118765 | Completed Phase 2 Results FDA Drug

• 1 other identifier: GSP304-201
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 25

Brief Summary

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)

Outcome Measures

Primary Outcomes (3)

• 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)

  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)

  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.

  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

  Day 1

• Amount (Aetau) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21

  Day 21

• Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 1

  Day 1

• Fraction of Dose (Fe) of Tiotropium Excreted in Urine Over the Dosing Interval on Day 21

  Day 21

• Peak Concentrations During the Dosing Interval (Cmax) on Day 1

  Day 1

Study Arms (5)

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

Interventions

GSP304 (tiotropium bromide) Inhalation Solution DRUG

Once daily (QD) oral inhalation using a nebulizer

Test Treatment T1: GSP304 Inhalation Solution; Test Treatment T2: GSP304 Inhalation Solution; Test Treatment T3: GSP304 Inhalation Solution

GSP304 Placebo Inhalation Solution DRUG

Once daily (QD) oral inhalation using a nebulizer

Test Treatment T4: GSP304 Placebo Inhalation Solution

Spiriva® Respimat® inhalation spray DRUG

Once daily (QD) oral inhalation

Test Treatment T5: Spiriva® Respimat® inhalation spray

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Glenmark Specialty S.A.: lead

Study Sites (25)

Glenmark Investigational Site 23

Andalusia, Alabama, 36420, United States

Location

Glenmark Investigational Site 12

Phoenix, Arizona, 85006, United States

Location

Glenmark Investigational Site 14

Tempe, Arizona, 85283, United States

Location

Glenmark Investigational Site 17

Fullerton, California, 92835, United States

Location

Glenmark Investigational Site 19

Edgewater, Florida, 32132, United States

Location

Glenmark Investigational Site 24

Miami, Florida, 33144, United States

Location

Glenmark Investigational Site 16

Miami, Florida, 33186, United States

Location

Glenmark Investigational Site 10

Miami Lakes, Florida, 33016, United States

Location

Glenmark Investigational Site 6

Orlando, Florida, 32825, United States

Location

Glenmark Investigational Site 20

Ormond Beach, Florida, 32124, United States

Location

Glenmark Investigational Site 21

Vero Beach, Florida, 32960, United States

Location

Glenmark Investigational Site 13

Winter Park, Florida, 32789, United States

Location

Glenmark Investigational Site 18

Las Vegas, Nevada, 89119, United States

Location

Glenmark Investigational Site 9

Charlotte, North Carolina, 28207, United States

Location

Glenmark Investigational Site 5

Columbus, Ohio, 43213, United States

Location

Glenmark Investigational Site 22

Columbus, Ohio, 43215, United States

Location

Glenmark Investigational Site 8

Dublin, Ohio, 43016, United States

Location

Glenmark Investigational Site 11

Medford, Oregon, 97504-9741, United States

Location

Glenmark Investigational Site 3

Easley, South Carolina, 29640, United States

Location

Glenmark Investigational Site 2

Greenville, South Carolina, 29615, United States

Location

Glenmark Investigational Site 4

Greenville, South Carolina, 29615, United States

Location

Glenmark Investigational Site 1

Rock Hill, South Carolina, 29732, United States

Location

Glenmark Investigational Site 15

Spartanburg, South Carolina, 29303, United States

Location

Glenmark Investigational Site 7

Spartanburg, South Carolina, 29303, United States

Location

Glenmark Investigational Site 25

Tomball, Texas, 77375, United States

Location

MeSH Terms

Interventions

Tiotropium Bromide

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Glenmark Pharmaceuticals Ltd.

clinicaltrialsdisclosuredesk@glenmarkpharma.com

201-684 8000

Study Officials

• Cynthia Caracta, MD FCCP

  Glenmark Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• 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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: April 18, 2017
• Study Start: March 24, 2017
• Primary Completion: July 31, 2017
• Study Completion: July 31, 2017
• Last Updated: August 1, 2019
• Results First Posted: August 1, 2019

Record last verified: 2019-07

Locations

US (25)