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

Chronic Obstructive Pulmonary Disease, COPD Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03064113
• Other study ID #: 0059
• Secondary ID: ACTRN12611000482
• Status: Completed
• Phase: Phase 2
• Start date: May 2011
• Est. completion date: October 2011

Study information

• Verified date: February 2022
• Source: Viatris Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease, COPD
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Placebo

• TD-4208 700 µg

• TD-4208 350 µg

• Ipratropium 500 µg

Locations

Country	Name	City	State
New Zealand	P3 Research	Wellington

Sponsors (2)

Lead Sponsor	Collaborator
Mylan Inc.	Theravance Biopharma

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak Forced Expiratory Volume in One Second (FEV1) Relative to Baseline		From predose to 25 hours postdose
Secondary	Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo		12 hr and 24 hr
Secondary	Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo		12 hr and 24 hr
Secondary	Peak Expiratory Flow Rate (PEFR) From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1		12hr and 24hr
Secondary	Forced Expiratory Flow From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1		12hr and 24hr
Secondary	Forced Vital Capacity (FVC)		From predose to 25 hours postdose
Secondary	Area Under the Forced Vital Capacity (FVC) vs. Time Curve		0-24 hours