Evaluation of S-600918 in Adults With Refractory Chronic Cough

Shionogi406 enrolled

Overview

The primary objective of this study is to determine the optimal dose of S-600918 in patients with refractory chronic cough by evaluating the change from baseline in 24-hour cough frequency (coughs per hour) with S-600918 compared with placebo.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

406

Conditions

Chronic Cough

Interventions

S-600918DRUG

Tablets for oral administration

Placebo to S-600918DRUG

Tablets for oral administration

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Having refractory chronic cough (including unexplained chronic cough) for at least 1 year. * If female and of childbearing potential, agreement to use one of the allowed contraceptive methods. * Capable of giving signed informed consent. Key Exclusion Criteria: * Currently smokes or uses potentially irritating inhalational agents (eg, e-cigarettes, smokeless cigarettes, vaping); stopped smoking or using potentially irritating inhalational agents within the last year; or has a smoking history of 20 pack-years or more. * Has chronic obstructive pulmonary disease or uncontrolled asthma. * Has a clinically unstable medical condition. * History of or ongoing significant psychiatric disorder. * History of respiratory tract infection or significant change in lung function or a pulmonary condition in the last 4 weeks. * History of malignancy in the last 5 years. * History of severe drug allergy. * History of alcohol or drug abuse in the last year or currently uses any form of marijuana or illicit drugs. * Has a clinically significant finding on a chest x-ray or chest computed tomography (CT) scan in the last year. * Has systolic blood pressure \> 160 mm Hg or diastolic blood pressure \> 90 mm Hg. * Received S-600918 previously. * Received an investigational drug in the last 3 months. * Received an angiotensin converting enzyme (ACE) inhibitor in the last 3 months or requires such treatment. * Has a positive serologic test for human immunodeficiency virus (HIV) antigen or antibody, hepatitis B virus surface antigen, or hepatitis C virus ribonucleic acid (RNA). * If female, pregnant or trying to become pregnant or breastfeeding.

Locations (136)

Outcomes

Primary Outcomes

Percent Change in Number of Coughs Per Hour in 24 Hours Following 4 Weeks of Study Treatment

Change in cough was calculated based upon the number of coughs per hour in 24 hours at Week 4 and baseline. Results are presented as percent change from baseline. Reported percent change is based on a mixed model for the log-transformed ratio of the number of coughs per hour in 24 hours at each visit with treatment, week, and treatment-by-week as fixed effect, participant as random effect, and region (Japan, Europe, or the United States) and the log-transformed coughs per hour in 24 hours at baseline as covariates. The number of coughs per hour while awake was measured using a cough monitor.

Time frame: Baseline to Week 4

Secondary Outcomes

Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment

The number of coughs per hour for 24 hours was measured using a cough monitor.

Time frame: Baseline to Week 4

Percent Change in Number of Coughs Per Hour While Awake Following 4 Weeks of Study Treatment

Change in cough was calculated based upon the number of coughs per hour in 24 hours at Week 4 and baseline. Results are presented as percent change from baseline. Reported percent change is based on a mixed model for the log-transformed ratio of the number of coughs per hour while awake at each visit with treatment, week, and treatment-by-week as fixed effect, participants as random effect, and region and the log-transformed coughs per hour while awake at baseline as covariates. The number of coughs per hour while awake was measured using a cough monitor.

Time frame: Baseline to Week 4

Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment

The number of coughs per hour while awake was measured using a cough monitor.

Time frame: Baseline to Week 4

Data from ClinicalTrials.gov

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Research Solutions of Arizona

Litchfield Park, Arizona, United States

Pulmonary Associates, PA

Phoenix, Arizona, United States

Alliance for Multispecialty Research

Tempe, Arizona, United States

Southern California Institute For Respiratory Diseases, Inc.

Los Angeles, California, United States

Allergy & Asthma Associates of Southern California dba Southern California Research

Mission Viejo, California, United States

California Medical Research Associates, Inc.

Northridge, California, United States

Center for Clinical Trials, LLC

Paramount, California, United States

Institute of HealthCare Assessment, Inc.

San Diego, California, United States

Sher Allergy Specialist/Center for Cough

Largo, Florida, United States

Medical Research Of Central Florida, LLC

Leesburg, Florida, United States

...and 126 more locations

Percent Change in Number of Coughs Per Hour While Asleep Following 4 Weeks of Study Treatment

Change in cough was calculated based upon the number of coughs per hour in 24 hours at Week 4 and baseline. Results are presented as percent change from baseline. Reported percent change is based on a mixed model for the log-transformed ratio of the number of coughs per hour while asleep at each visit with treatment, week, and treatment-by-week as fixed effect, participants as random effect, and region and the log-transformed coughs per hour while asleep at baseline as covariates. The number of coughs per hour while awake was measured using a cough monitor.

Time frame: Baseline to Week 4

Change From Baseline in Weekly Cough Severity Following 4 Weeks of Study Treatment

Cough severity was assessed by the participant by a visual analog scale with numbers from 0 to 100. Results are presented as change from baseline. Reported change is based on a mixed model for the change in weekly cough severity score after 4 weeks of treatment with treatment, week, and treatment-by-week as fixed effect, participant as random effect, and region (Japan, Europe, or the United States) and the severity score at baseline as covariates. Higher scores indicated higher cough severity.

Time frame: Baseline to Week 4

Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score

The LCQ is a patient-reported quality of life (QOL) measure of chronic cough. The questionnaire consists of 19 items to which the participant responds on a 7-point Likert response scale (from 1 to 7). Each item assesses symptoms during cough and the effect of cough on 3 main domains: physical, psychological and social. Domain scores range from 1-7, and the total score ranges from 3 - 21. Higher score indicates a better quality of life. Results are presented as change from baseline. Reported change is based on a mixed model for the change in LCQ Total Score after 4 weeks of treatment with treatment, week, and treatment-by-week as fixed effect, participant as random effect, and region (Japan, Europe, or the United States) and the LCQ Score of corresponding domain at baseline as covariates.

Time frame: Baseline to Week 4

Number of Responders Defined as Participants With an Increase in LCQ of ≥ 1.3 Points

Time frame: Baseline to Week 4

Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF)

The ICIQ-SF is a questionnaire used to evaluate the frequency, severity, and impact of urinary incontinence on the quality of life. The questionnaire includes 3 items with responses measured on Likert scales, and 1 item that is measured via a qualitative response. The 3 nominal responses are summed to give the ICIQ score (this total ICIQ-SF score can range from 0 to 21), where a higher score indicates more severe symptoms. The 1 item remaining that is measured via qualitative response is not given a score; rather, the participant selects 1 description out of 8 possible descriptions of this item.

Time frame: Baseline to Week 4

Change From Baseline in Short Form (36) Health Survey (SF-36)

The SF-36 is a 36-item questionnaire to assesses a participant's health status using 8 health concepts: limitations in physical activities because of health problems; limitations in social activities because of physical or emotional problems; limitations in usual role activities because of physical health problems; bodily pain; general mental health (psychological distress and well-being); limitations in usual role activities because of emotional problems; vitality (energy and fatigue); and general health perceptions. The mental component reports the average of all the emotionally relevant items and the physical component reports the average of all the physically relevant items. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 indicates no disability. Median change can range from -100 to 100. A positive median change indicates an improved outcome.

Time frame: Baseline to Week 4

Number of Responders as Assessed by Patient Global Impression of Change (PGIC)

The PGIC is a patient-reported measure of overall health status and consists of 1 item adapted from the Clinical Global Impressions scale. The participant selects 1 description out of 7 possible descriptions of this item. The descriptions are numbered from 1 through 7, where lower numbers indicate better quality of life. Participants were considered responders if they reported "Very much improved", "Much improved", or "Minimally improved" from baseline on the PGIC assessment.

Time frame: Week 4