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

NCT ID: NCT03064113

Last Updated: 2022-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2011-10-31

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.

Conditions

Chronic Obstructive Pulmonary Disease, COPD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sequence 1

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

TD-4208 700 μg

Intervention Type: DRUG

TD-4208 350 μg

Intervention Type: DRUG

Ipratropium 500 μg

Intervention Type: DRUG

Sequence 2

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

TD-4208 700 μg

Intervention Type: DRUG

TD-4208 350 μg

Intervention Type: DRUG

Ipratropium 500 μg

Intervention Type: DRUG

Sequence 3

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

TD-4208 700 μg

Intervention Type: DRUG

TD-4208 350 μg

Intervention Type: DRUG

Ipratropium 500 μg

Intervention Type: DRUG

Sequence 4

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

TD-4208 700 μg

Intervention Type: DRUG

TD-4208 350 μg

Intervention Type: DRUG

Ipratropium 500 μg

Intervention Type: DRUG

Interventions

Placebo

Intervention Type: DRUG

TD-4208 700 μg

Intervention Type: DRUG

TD-4208 350 μg

Intervention Type: DRUG

Ipratropium 500 μg

Intervention Type: DRUG

Other Intervention Names

Revefenacin; Revefenacin

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Theravance Biopharma

INDUSTRY

Sponsor Role: collaborator

Mylan Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Theravance Biopharma

Locations

P3 Research

Wellington, , New Zealand

Countries

New Zealand

References

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.

Reference Type: DERIVED

PMID: 33124005 (View on PubMed)

Other Identifiers

ACTRN12611000482965

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1120-8290

Identifier Type: OTHER

Identifier Source: secondary_id

0059

Identifier Type: -

Identifier Source: org_study_id