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Effects of TD-4208 on FEV1 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Primary Purpose

Chronic Obstructive Pulmonary Disease, COPD

Status

Completed

Phase

Phase 2

Locations

New Zealand

Study Type

Interventional

Intervention

Placebo

TD-4208 700 μg

TD-4208 350 μg

Ipratropium 500 μg

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease, COPD focused on measuring Chronic Obstructive Pulmonary Disease, COPD

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis of moderate stable Chronic Obstructive Pulmonary.
Disease with FEV1/FVC <0.7 at screening.
Woman of non-childbearing potential.
Female participants of childbearing potential must test negative for pregnancy and must be using a highly effective method of birth control during the study and for at least 1 month after completion of study dosing.
Female participants must not be breastfeeding.
Men must agree to use a highly effective method of birth control with partners of childbearing potential during the study and for 1 month after completion of study dosing.
Current or past smoking history >10 pack-years.
Must be capable of performing reproducible spirometry maneuvers.

Exclusion Criteria:

History of significant respiratory disease other than COPD, and/ or requires daily long-term oxygen therapy.
Exacerbation of COPD, lung infection within 6 weeks prior to study.
Start of or change in dose of COPD treatment 4 weeks before study.
Daily using of maintenance systemic/inhaled corticosteroids (>1000 microgram of fluticasone propionate equivalent or >5 mg prednisone).
Use of bronchodilators or medication for the treatment of COPD, aspirin, anti-inflammatories for a specific time, prior to the first dose or is not willing to abstain from their use for the specified time periods prior to study dose administration.
Symptomatic prostrate hypertrophy, bladder neck obstruction, active cancer, narrow angle glaucoma.
Clinical significant hypersensitivity to medications.
Participants have an uncontrolled hematologic, immunologic, renal, neurologic, hepatic, endocrine or other disease that may place participant at risk.
Cerebrovascular, cardiovascular disease or abnormal ECG.
History of drug or alcohol abuse.

Sites / Locations

P3 Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Sequence 1

Sequence 2

Sequence 3

Sequence 4

Arm Description

Period 1 = Placebo; Period 2 = TD-4208 700 μg; Period 3 = TD-4208 350 μg; Period 4 = Ipratropium 500 μg

Period 1 = TD-4208 700 μg; Period 2 = Ipratropium 500 μg; Period 3 = Placebo; Period 4 = TD-4208 350 μg

Period 1 = TD-4208 350 μg; Period 2 = Placebo; Period 3 = Ipratropium 500 μg; Period 4 = TD-4208 700 μg

Period 1 = Ipratropium 500 μg; Period 2 = TD-4208 350 μg; Period 3 = TD-4208 700 μg; Period 4 = Placebo

Outcomes

Primary Outcome Measures

Peak Forced Expiratory Volume in One Second (FEV1) Relative to Baseline

Secondary Outcome Measures

Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo

Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo

Peak Expiratory Flow Rate (PEFR) From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1

Forced Expiratory Flow From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1

Forced Vital Capacity (FVC)

Area Under the Forced Vital Capacity (FVC) vs. Time Curve

Full Information

NCT ID

NCT03064113

First Posted

January 20, 2017

Last Updated

February 22, 2022

Sponsor

Mylan Inc.

Collaborators

Theravance Biopharma

1. Study Identification

Unique Protocol Identification Number

NCT03064113

Brief Title

Effects of TD-4208 on FEV1 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Official Title

A Phase 2, Randomized, Double-Blind, Crossover Study to Examine the Pharmacodynamics, Safety and Tolerability, and Pharmacokinetics of Single Doses of TD-4208 in Subjects Diagnosed With Chronic Obstructive Pulmonary Disease

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Completed

Study Start Date

May 2011 (undefined)

Primary Completion Date

October 2011 (Actual)

Study Completion Date

October 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mylan Inc.

Collaborators

Theravance Biopharma

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Thirty-two subjects diagnosed with COPD were enrolled, received each study treatment and completed the follow-up assessments. During each of the four study periods, subjects were admitted to the clinic on Day -1 and housed overnight until after the last spirometry measurement. Serial pulmonary function tests were performed and PK (pharmacokinetics) samples collected up to 25 hours. Subjects were discharged from the clinic on Day 2 after evaluations.

Detailed Description

Subjects were assigned to one of the 4-treatment sequence groups presented in the table above according to a randomization schedule supplied by the Sponsor before study initiation. The randomization scheme did not include assignments for replacement subjects. Subjects reported to their respective clinical research unit (CRU) on Admission/Day -1 for pre-randomization procedures and confirmation of eligibility (and continued eligibility for Periods 2 to 4). The unblinded pharmacist prepared and dispensed the nebulizers, according to the randomization schedule for each of the 4 periods. Dosing occurred in the morning, generally between 7 am and 9 am. For Periods 2 to 4, dosing occurred within ±30 minutes of the dosing time established in Period 1. Study drug was administered in the respective CRU under the supervision of study personnel. Single doses of TD-4208, ipratropium bromide, and placebo were administered in the clinical research unit (CRU) under the supervision of study personnel. Care was taken to avoid eye contact with study drugs. Residual drug solution remaining in the nebulizer (ie, in mL) was measured and recorded. The investigator or designee was responsible for maintaining accountability records for all study drug(s) in accordance with applicable government regulations and study procedures. The accountability record included entries for receipt, distribution or dispensing, and destruction of the material(s). Unused and expired study drugs were to be disposed of in accordance with written instructions from the Sponsor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Obstructive Pulmonary Disease, COPD

Keywords

Chronic Obstructive Pulmonary Disease, COPD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sequence 1

Arm Type

Experimental

Arm Description

Period 1 = Placebo; Period 2 = TD-4208 700 μg; Period 3 = TD-4208 350 μg; Period 4 = Ipratropium 500 μg

Arm Title

Sequence 2

Arm Type

Experimental

Arm Description

Period 1 = TD-4208 700 μg; Period 2 = Ipratropium 500 μg; Period 3 = Placebo; Period 4 = TD-4208 350 μg

Arm Title

Sequence 3

Arm Type

Experimental

Arm Description

Period 1 = TD-4208 350 μg; Period 2 = Placebo; Period 3 = Ipratropium 500 μg; Period 4 = TD-4208 700 μg

Arm Title

Sequence 4

Arm Type

Experimental

Arm Description

Period 1 = Ipratropium 500 μg; Period 2 = TD-4208 350 μg; Period 3 = TD-4208 700 μg; Period 4 = Placebo

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Type

Drug

Intervention Name(s)

TD-4208 700 μg

Other Intervention Name(s)

Revefenacin

Intervention Type

Drug

Intervention Name(s)

TD-4208 350 μg

Other Intervention Name(s)

Revefenacin

Intervention Type

Drug

Intervention Name(s)

Ipratropium 500 μg

Primary Outcome Measure Information:

Title

Peak Forced Expiratory Volume in One Second (FEV1) Relative to Baseline

Time Frame

From predose to 25 hours postdose

Secondary Outcome Measure Information:

Title

Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo

Time Frame

12 hr and 24 hr

Title

Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo

Time Frame

12 hr and 24 hr

Title

Peak Expiratory Flow Rate (PEFR) From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1

Time Frame

12hr and 24hr

Title

Forced Expiratory Flow From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1

Time Frame

12hr and 24hr

Title

Forced Vital Capacity (FVC)

Time Frame

From predose to 25 hours postdose

Title

Area Under the Forced Vital Capacity (FVC) vs. Time Curve

Time Frame

0-24 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis of moderate stable Chronic Obstructive Pulmonary. Disease with FEV1/FVC <0.7 at screening. Woman of non-childbearing potential. Female participants of childbearing potential must test negative for pregnancy and must be using a highly effective method of birth control during the study and for at least 1 month after completion of study dosing. Female participants must not be breastfeeding. Men must agree to use a highly effective method of birth control with partners of childbearing potential during the study and for 1 month after completion of study dosing. Current or past smoking history >10 pack-years. Must be capable of performing reproducible spirometry maneuvers. Exclusion Criteria: History of significant respiratory disease other than COPD, and/ or requires daily long-term oxygen therapy. Exacerbation of COPD, lung infection within 6 weeks prior to study. Start of or change in dose of COPD treatment 4 weeks before study. Daily using of maintenance systemic/inhaled corticosteroids (>1000 microgram of fluticasone propionate equivalent or >5 mg prednisone). Use of bronchodilators or medication for the treatment of COPD, aspirin, anti-inflammatories for a specific time, prior to the first dose or is not willing to abstain from their use for the specified time periods prior to study dose administration. Symptomatic prostrate hypertrophy, bladder neck obstruction, active cancer, narrow angle glaucoma. Clinical significant hypersensitivity to medications. Participants have an uncontrolled hematologic, immunologic, renal, neurologic, hepatic, endocrine or other disease that may place participant at risk. Cerebrovascular, cardiovascular disease or abnormal ECG. History of drug or alcohol abuse.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Monitor

Organizational Affiliation

Theravance Biopharma

Official's Role

Study Director

Facility Information:

Facility Name

P3 Research

City

Wellington

ZIP/Postal Code

6021

Country

New Zealand

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

33124005

Citation

Lo A, Borin MT, Bourdet DL. Population Pharmacokinetics of Revefenacin in Patients with Chronic Obstructive Pulmonary Disease. Clin Pharmacokinet. 2021 Mar;60(3):391-401. doi: 10.1007/s40262-020-00938-3.

Results Reference

derived

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Effects of TD-4208 on FEV1 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

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