Revefenacin in Chinese Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease(COPD)

Phase 3

Completed

Conditions: COPD

Interventions: Drug: Revefenacin 175 mcg in 3 ML Inhalation Solution
Drug: Placebo inhalation solution QD

Registration Number: NCT05046795

Lead Sponsor: Mylan Pharma UK Ltd.

Brief Summary: This study is a phase III clinical study to assess the efficacy and safety of Revefenacin inhalation solution 175 mcg administered once daily via nebulization for 12 weeks compared to placebo in a population of Chinese subjects with moderate to very severe COPD.

Detailed Description: This will be a multi-center, randomized, double blind, placebo-controlled, parallel group study, randomizing approximately 320 male or female moderate-very severe COPD subjects. Subjects will receive study drug for 12 weeks. Treatments to be received during the study will include one of the following, administered using a centrally-provided, standard jet nebulizer and compressor via a mouthpiece: A. Revefenacin inhalation solution 175 mcg Quaque die (QD). B. Placebo inhalation solution QD. Subjects will have approximately 6 clinic visits (encompassing a screening period of up to 30 days and a treatment period of 12 weeks), and a follow-up telephone call 1-2 weeks after the End of Treatment (EoT) visit.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 258

Inclusion Criteria

Key inclusion criteria include:
- Males and females of Chinese ethnicity, at least 40 years of age. Females may be of either childbearing or non-childbearing potential. All females of childbearing potential must be using an acceptable, highly effective method of contraception and have a negative pregnancy test at screening.
- A clinical diagnosis for at least 6 months prior to screening of COPD according to Global Initiative for Chronic Obstructive Lung Disease(GOLD) guidelines.
- Subject is capable of performing reproducible spirometry maneuvers as described by current American Thoracic Society/European Respiratory Society (ATS/ERS) Guidelines and has a post-ipratropium (500 mcg nebulized) Forced Expiratory Volume in
  
  1 second(FEV1)/Forced Vital Capacity(FVC) ratio <0.7 at Visit 2.
- Subject has moderate to very severe COPD with a post-ipratropium (500 mcg nebulized) FEV1 less than 80% of predicted normal (using the Global Lung Function Initiative reference range; ) and an absolute FEV1 >700 mL at Visit 2
- Current smoker or ex-smoker, with a history of at least 10 pack-years of tobacco smoking. Ex-smokers must have stopped smoking >6 months prior to Visit 1.

Exclusion Criteria

Key exclusion criteria include:
- Previously dosed with Revefenacin.
- Current diagnosis of asthma.
- Alpha-1 anti-trypsin deficiency.
- Other chronic or active respiratory disorder (e.g., clinically significant [as determined by the Investigator] bronchiectasis, pulmonary fibrosis, sarcoidosis, pneumoconiosis, active tuberculosis).
- Symptoms of, or treatment for an Acute Exacerbation of COPD(AECOPD) requiring antibiotics and/or oral/systemic corticosteroids or in-patient hospitalization during the 28 days preceding screening or during the screening period between Visit 1 and Visit 3.
- Pneumonia requiring hospitalization within 28 days prior to screening or during the screening period between Visit 1 and Visit 3.
- Lower respiratory tract infection requiring treatment with antibiotics during the 28 days preceding screening or during the screening period between Visit 1 and Visit 3.
- History or presence of pulmonary hypertension, respiratory failure, cor pulmonale or right ventricular failure which may impact the safety of the subject in the clinical judgement of the Investigator.
- History of pulmonary lobectomy, lung volume reduction surgery, or lung transplantation.
- Use of supplemental oxygen therapy for more than 15 hours per day (includes night-time use).
- Subjects with hepatic impairment.
- Subject suffers from any medical condition that would preclude the use of inhaled anticholinergics, including narrow-angle glaucoma, symptomatic benign prostatic hyperplasia, bladder neck obstruction, or urinary retention.
- Subjects who are unable to stop any of the following medications, and refrain from their use throughout the study until the final dose of study drug:
  - Short-acting β2 agonists (except study-supplied salbutamol).
  - Short-acting anticholinergic agents (except those used for reversibility testing).
  - Long-acting anticholinergics (except study supplied medication).
  - Combination β2 agonists/anticholinergic agents.
  - Combination β2 agonists/inhaled corticosteroids/anticholinergic agents.
  - Phosphodiesterase 4 inhibitors.
  - Theophyllines.
  - Leukotriene inhibitors.
  - Orally inhaled nedocromil or cromolyn sodium.
  - Oral or parenteral corticosteroids.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Revefenacin inhalation solution 175 mcg QD.	Revefenacin 175 mcg in 3 ML Inhalation Solution	Revefenacin inhalation solution 175 mcg QD.
Placebo inhalation solution QD.	Placebo inhalation solution QD	Placebo inhalation solution QD.

Primary Outcome Measures

Name	Time	Method
Trough FEV1 on Day 85	Baseline and Day 85	Change from Baseline (Day 1, pre-dose) trough FEV1 on Day 85
Trough FEV1 on Day 85 - Sensitivity Analysis With Missing Data Imputed	Baseline, Day 29, Day 57 and Day 85	Sensitivity analysis results of change from baseline in trough FEV1 (mL) on Day 85 with missing data imputed by last observation carried forward

Secondary Outcome Measures

Name	Time	Method
Trough FVC on Day 85	Baseline and Day 85	Change from baseline (Day 1, pre-dose) trough Forced Vital Capacity (FVC) on Day 85
Change From Baseline in Peak FEV1 (0-2h) on Day 1	Day 1, from 45 minutes before dosing to 2 hours after dosing	Baseline FEV1 was defined as the average of the -45 and -15 minute measurements prior to dosing of study drug on Day 1. Peak FEV1 (0-2h) was defined as the highest post dose FEV1 value within 2 hours after the dosing.
Change From Baseline in Peak FEV1 (0-2h) on Day 85	Day 1 (baseline) and Day 85, from 45 minutes before dosing to 2 hours after dosing	Baseline FEV1 was defined as the average of the -45 and -15 minute measurements prior to dosing of study drug on Day 1. Peak FEV1 (0-2h) was defined as the highest post dose FEV1 value within 2 hours after the dosing.
Change From Baseline in SGRQ Total Score on Day 85	Day 1 (baseline) and Day 85	Change from Baseline in the St George's Respiratory Questionnaire (SGRQ) Total Score on Day 85. Scores range from 0 to 100, with higher scores indicating more health limitations. A reduction of 4 or more points is considered to be a clinically meaningful improvement
Number (%) of SGRQ Responders on Day 85	Day 85	Number of subjects with a decrease from baseline of ≥4 units in SGRQ total score (which was defined as a responder) on Day 85

Trial Locations

Locations (35): Wuxi People's Hospital
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Wuxi, Jiangsu, China
Yangzhou First People's Hospital
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Yangzhou, Jiangsu, China
Peking University Third Hospital
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Beijing, Beijing, China
Beijing Hospital
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Beijing, Beijing, China
Guangzhou First People's Hospital
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Guangzhou, Guangdong, China
The Second Affiliated Hospital Of Guangzhou Medical University
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Guangzhou, Guangdong, China
The First Affiliated Hospital of Guangzhou Medical University
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Guangzhou, Gunagdong, China
The First Hospital of Changsha
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Changsha, Hunan, China
Inner Mongolia Baogang Hospital
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Baotou, Inner Mongolia, China
Inner Mongolia People's Hospital
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Hohhot, Inner Mongolia, China
Affiliated Hospital of Inner Mongolia Medical College
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Hohhot, Inner Mongolia, China
Jiangsu Jiangyin People's Hospital
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Jiangyin, Jiangsu, China
Zhongda Hospital, Southeast University - Pulmonology
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Nanjing, Jiangsu, China
Jiangxi Provincial People's Hospital
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Nanchang, Jiangxi, China
Nanchang University - The Second Affiliated Hospital
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Nanchang, Jiangxi, China
Jiangxi Pingxiang People's Hospital
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Pingxiang, Jiangxi, China
The First Bethune Hospital of Jilin University
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Changchun, Jilin, China
Shanghai Pudong New Area People's Hospital
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Shanghai, Shanghai, China
Shengjing Hospital of China Medical University
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Shenyang, Liaoning, China
Sichuan University - West China Hospital
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Chengdu, Sichuan, China
Tianjin Medical University General Hospital - Respiration
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Tianjin, Tianjin, China
The First Center hospital of Tianjin
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Tianjin, Tianjin, China
The First Affiliated Hospital of Xinjiang Medical University - Hospital
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Urumqi, Xinjiang, China
Xinhua Hostipal of Zhejiang Province
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Hangzhou, Zhejiang, China
Dongyang People's Hospital
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Dongyang, Zhejiang, China
Huzhou Central Hospital
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Huzhou, Zhejiang, China
Anhui Medical University - Hefei First People's Hospital
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Hefei, Anhui, China
The Third Affiliated Hospital Of Guangzhou Medical University
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Guangzhou, Guangdong, China
Hainan General Hospital
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Haikou, Hainan, China
Affiliated Hospital of Guangdong Medical University
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Guangzhou, Guangdong, China
The First Affiliated Hospital of Baotou Medical College - Respiration
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Baotou, Inner Mongolia, China
Nanjing Jiangning Hospital
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Nanjing, Jiangsu, China
The First Hospital of China Medical University
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Shenyang, Liaoning, China
Yanbian university hospital
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Yanji, Jilin, China
Shanghai East Hospital
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Shanghai, Shanghai, China