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

NCT03064113 | Completed Phase 2 Results

• 3 other identifiers: 0059ACTRN12611000482965U1111-1120-8290
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Obstructive Pulmonary Disease, COPD

Keywords

Chronic Obstructive Pulmonary Disease, COPD

Outcome Measures

Primary Outcomes (1)

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

  From predose to 25 hours postdose

Secondary Outcomes (6)

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

  12 hr and 24 hr

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

  12 hr and 24 hr

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

  12hr and 24hr

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

  12hr and 24hr

• Forced Vital Capacity (FVC)

  From predose to 25 hours postdose

Study Arms (4)

Sequence 1

EXPERIMENTAL

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

Drug: Placebo; Drug: TD-4208 700 μg; Drug: TD-4208 350 μg; Drug: Ipratropium 500 μg

Sequence 2

EXPERIMENTAL

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

Drug: Placebo; Drug: TD-4208 700 μg; Drug: TD-4208 350 μg; Drug: Ipratropium 500 μg

Sequence 3

EXPERIMENTAL

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

Drug: Placebo; Drug: TD-4208 700 μg; Drug: TD-4208 350 μg; Drug: Ipratropium 500 μg

Sequence 4

EXPERIMENTAL

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

Drug: Placebo; Drug: TD-4208 700 μg; Drug: TD-4208 350 μg; Drug: Ipratropium 500 μg

Interventions

Placebo DRUG

Sequence 1; Sequence 2; Sequence 3; Sequence 4

TD-4208 700 μg DRUG

Also known as: Revefenacin

Sequence 1; Sequence 2; Sequence 3; Sequence 4

TD-4208 350 μg DRUG

Also known as: Revefenacin

Sequence 1; Sequence 2; Sequence 3; Sequence 4

Ipratropium 500 μg DRUG

Sequence 1; Sequence 2; Sequence 3; Sequence 4

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mylan Inc.: lead
• Theravance Biopharma: collaborator

Study Sites (1)

P3 Research

Wellington, 6021, New Zealand

Location

Related Publications (1)

• 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.

  PMID: 33124005 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

revefenacin; Ipratropium

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Head of Clinical Development & Medical Affairs
• Organization: Theravance Biopharma

medinfo@theravance.com

1-855-633-8479

Study Officials

• Medical Monitor

  Theravance Biopharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• 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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: February 24, 2017
• Study Start: May 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: February 24, 2022
• Results First Posted: November 14, 2019

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1)