7 Days of TD-4208 in Subjects With Chronic Obstructive Pulmonary Disease

NCT01704404 | Completed Phase 2 Results

• 1 other identifier: 0091
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

This study will characterize the dose response of TD-4208 after 7 days of dosing in subjects with Chronic Obstructive Pulmonary Disease (COPD).

Conditions

COPD

Keywords

Long acting muscarinic antagonist; Chronic Bronchitis; Emphysema; Chronic Obstructive Pulmonary Disease; COPD

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Day 7 in Trough FEV1 (Forced Expiratory Volume in 1 Second)

  From baseline to day 7

Other Outcomes (3)

• Cmax

  From baseline to day 7

• Tmax

  From baseline to day 7

• Plasma Half-life

  From baseline to day 7

Study Arms (7)

Dose 1 TD-4208

EXPERIMENTAL

22 µg

Drug: TD-4208

Dose 2 TD-4208

EXPERIMENTAL

44 µg

Drug: TD-4208

Dose 3 TD-4208

EXPERIMENTAL

88 µg

Drug: TD-4208

Dose 4 TD-4208

EXPERIMENTAL

175 µg

Drug: TD-4208

Dose 5 TD-4208

EXPERIMENTAL

350 µg

Drug: TD-4208

Dose 6 TD-4208

EXPERIMENTAL

700 µg

Drug: TD-4208

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

TD-4208 DRUG

Also known as: revefenacin

Dose 1 TD-4208; Dose 2 TD-4208; Dose 3 TD-4208; Dose 4 TD-4208; Dose 5 TD-4208; Dose 6 TD-4208

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• Subject is a male or female between the ages of 40 and 75 years (inclusive, at randomization).
• Subject:
• Has an FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) \<0.7 at screening; and
• Has a post-bronchodilator FEV1 at screening of between 30% and 80% (inclusive) of the predicted normal value.
• Subject demonstrates at screening at least a 120 mL increase in FEV1 within 1 hour of receiving 500 µg of ipratropium bromide from a PARI LC Sprint® nebulizer.
• Females of non-childbearing potential. All male subjects 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.
• Subject (or care giver) is able to properly prepare and administer study medication.
• Subject is willing and able to give written informed consent to participate.

You may not qualify if:

• Subject has had a COPD exacerbation or lung infection within 6 weeks before randomization.
• Subject has had an initiation of treatment, or a change in dose, of an inhaled or oral corticosteroid, or long-acting beta2 agonist (LABA), or long-acting muscarinic antagonist (LAMA) within 4 weeks before the qualifying ipratropium bromide response test.
• Subject is taking daily maintenance inhaled/systemic corticosteroids (\>1000 μg of fluticasone propionate equivalent or ≥10 mg prednisone).
• Subject has an uncontrolled hematologic, immunologic, renal, neurologic, hepatic, endocrine, or other disease or condition based on information gathered from the medical history, physical examination, or laboratory findings that might place the subject at undue risk or potentially compromise the results or interpretation of the study.
• Subject has a history of significant cerebrovascular disease, coronary artery disease, or cardiac arrhythmias. Subject has a history (or family history) of congenital prolonged QTc (corrected QT interval) syndrome or has an abnormal clinically significant electrocardiogram (ECG) at screening, including QTcB (QT interval corrected for heart rate using Bazett's formula) value \>450 msec (males) or \>470 msec (females); or shows evidence of clinically significant rhythm abnormality.
• Subject has a known hypersensitivity to TD-4208 or similar drug class.
• Subject has a history of alcoholism or drug abuse within 2 years prior to screening.

Sponsors & Collaborators

• Mylan Inc.: lead
• Theravance Biopharma: collaborator

Study Sites (1)

P3 Research Ltd

Wellington, New Zealand

Location

Related Publications (2)

• 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

• Quinn D, Barnes CN, Yates W, Bourdet DL, Moran EJ, Potgieter P, Nicholls A, Haumann B, Singh D. Pharmacodynamics, pharmacokinetics and safety of revefenacin (TD-4208), a long-acting muscarinic antagonist, in patients with chronic obstructive pulmonary disease (COPD): Results of two randomized, double-blind, phase 2 studies. Pulm Pharmacol Ther. 2018 Feb;48:71-79. doi: 10.1016/j.pupt.2017.10.003. Epub 2017 Oct 4.

  PMID: 28987804 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Bronchitis, Chronic; Emphysema

Interventions

revefenacin

Condition Hierarchy (Ancestors)

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

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: October 4, 2012
• First Posted: October 11, 2012
• Study Start: December 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: December 1, 2013
• Last Updated: February 24, 2022
• Results First Posted: March 13, 2017

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1)