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

• ClinicalTrials.gov Identifier: NCT01704404
• Recruitment Status: Completed
• First Posted: October 11, 2012
• Results First Posted: March 13, 2017
• Last Update Posted: November 26, 2019
• Sponsor: Theravance Biopharma
• Information provided by (Responsible Party): Theravance Biopharma

Study Description

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).

Condition or disease	Intervention/treatment	Phase
COPD	Drug: TD-4208; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of the Pharmacodynamics, Safety and Tolerability, and Pharmacokinetics of Multiple Doses of TD-4208 for 7 Days in Subjects Diagnosed With Chronic Obstructive Pulmonary Disease
• Study Start Date: December 2012
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose 1 TD-4208; 22 µg	Drug: TD-4208; Other Name: revefenacin
Experimental: Dose 2 TD-4208; 44 µg	Drug: TD-4208; Other Name: revefenacin
Experimental: Dose 3 TD-4208; 88 µg	Drug: TD-4208; Other Name: revefenacin
Experimental: Dose 4 TD-4208; 175 µg	Drug: TD-4208; Other Name: revefenacin
Experimental: Dose 5 TD-4208; 350 µg	Drug: TD-4208; Other Name: revefenacin
Experimental: Dose 6 TD-4208; 700 µg	Drug: TD-4208; Other Name: revefenacin
Placebo Comparator: Placebo; Placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to Day 7 in Trough FEV1 (Forced Expiratory Volume in 1 Second) [ Time Frame: From baseline to day 7 ]

Other Outcome Measures:

1. Cmax [ Time Frame: From baseline to day 7 ]

   Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.

   Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.

2. Tmax [ Time Frame: From baseline to day 7 ]

   Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.

   Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.

3. Plasma Half-life [ Time Frame: From baseline to day 7 ]

   Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.

   Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subject is a male or female between the ages of 40 and 75 years (inclusive, at randomization).

2. 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.
3. 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.
4. 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.
5. Subject (or care giver) is able to properly prepare and administer study medication.
6. Subject is willing and able to give written informed consent to participate.

Exclusion Criteria:

1. Subject has had a COPD exacerbation or lung infection within 6 weeks before randomization.
2. 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.
3. Subject is taking daily maintenance inhaled/systemic corticosteroids (>1000 μg of fluticasone propionate equivalent or ≥10 mg prednisone).
4. 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.
5. 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.
6. Subject has a known hypersensitivity to TD-4208 or similar drug class.
7. Subject has a history of alcoholism or drug abuse within 2 years prior to screening.

Contacts and Locations

Locations

New Zealand

P3 Research Ltd

Wellington, New Zealand

Sponsors and Collaborators

Theravance Biopharma

Investigators

• Study Director: Medical Monitor; Theravance Biopharma

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lo A, Borin MT, Bourdet DL. Population Pharmacokinetics of Revefenacin in Patients with Chronic Obstructive Pulmonary Disease. Clin Pharmacokinet. 2020 Oct 29. doi: 10.1007/s40262-020-00938-3. [Epub ahead of print]

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.

• Responsible Party: Theravance Biopharma
• ClinicalTrials.gov Identifier: NCT01704404
• Other Study ID Numbers: 0091
• First Posted: October 11, 2012
• Results First Posted: March 13, 2017
• Last Update Posted: November 26, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Theravance Biopharma:

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

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases