Study of the Efficacy, Safety, and Tolerability of Serlopitant for the Treatment of Refractory Chronic Cough

A Randomized, Double-blind, Placebo-controlled Study of the Efficacy, Safety, and Tolerability of Serlopitant for the Treatment of Refractory Chronic Cough

Study of the efficacy, safety, and tolerability of serlopitant for the treatment of refractory chronic cough

Study Overview

• Status: Completed
• Conditions: Refractory Chronic Cough
• Intervention / Treatment: Drug: 5 mg Serlopitant Tablets; Drug: Matching Placebo Tablets

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Study site 133
  • Birmingham, United Kingdom, B9 5SS
    • Study Site 139
  • Cottingham, United Kingdom, HU16 5JQ
    • Study Site 136
  • Llanelli, United Kingdom, SA14 8QF
    • Study Site 141
  • London, United Kingdom, SE5 9RS
    • Study Site 138
  • London, United Kingdom, SW3 6HP
    • Study Site 137
  • Manchester, United Kingdom, M23 9LT
    • Study Site 132
  • Oxford, United Kingdom, OX3 7LE
    • Study Site 135
  • Preston, United Kingdom, PR2 9HT
    • Study Site 134
  • Taunton, United Kingdom, TA2 5DA
    • Study Site 140
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Study Site 130
    • Mission Viejo, California, United States, 92691
      • Study Site 128
    • San Diego, California, United States, 92108
      • Study site 123
    • San Jose, California, United States, 95117
      • Study Site 127
    • Stockton, California, United States, 95207
      • Study Site 131
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Study Site 106
    • Colorado Springs, Colorado, United States, 80907
      • Study site 113
    • Denver, Colorado, United States, 80230
      • Study Site 108
  • Florida
    • Largo, Florida, United States, 33778
      • Study Site 118
    • Winter Park, Florida, United States, 32789
      • Study Site 107
  • Minnesota
    • Plymouth, Minnesota, United States, 55441
      • Study site 115
    • Rochester, Minnesota, United States, 55905
      • Study site 110
  • New Jersey
    • Ocean Township, New Jersey, United States, 07712
      • Study Site 121
  • New York
    • Rochester, New York, United States, 14618
      • Study site 125
  • North Carolina
    • Charleston, North Carolina, United States, 29420
      • Study site 129
    • Charlotte, North Carolina, United States, 28207
      • Study Site 103
    • Gastonia, North Carolina, United States, 28054
      • Study site 111
    • Mooresville, North Carolina, United States, 28117
      • Study site 114
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Study Site 122
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Study site 112
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Study site 117
    • Portland, Oregon, United States, 97202
      • Study Site 116
  • South Carolina
    • Rock Hill, South Carolina, United States, 29732
      • Study Site 104
  • Texas
    • Dallas, Texas, United States, 75231
      • Study Site 102
    • Dallas, Texas, United States, 75231
      • Study Site 120
    • San Antonio, Texas, United States, 78229
      • Study Site 101
    • Waco, Texas, United States, 76712
      • Study Site 109
  • Washington
    • Bellingham, Washington, United States, 98225
      • Study site 126
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Study Site 105

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female and males between 18 and 80 years of age
• Have a diagnosis of treatment refractory chronic cough or unexplained cough for at least one year
• Chest radiograph or computed tomography (CT) Thorax within the last 5 years not demonstrating any abnormality considered to be significantly contributing to the chronic cough
• At Screening have a score of ≥ 40mm on the Cough Severity VAS
• At Baseline (Day 0) have a score of ≥ 40mm on the Cough Severity VAS
• All female subjects who are of childbearing potential must practice highly effective contraception (i.e., pregnancy prevention method with a failure rate of < 1% per year) from the time of the initial screening visit until 4 weeks after last dose of study drug. Please refer to the protocol for acceptable methods of contraception

Exclusion Criteria:

• Prior treatment with serlopitant or other NK1-R antagonist
• Presence of any medical condition or disability that could interfere with study
• History of hypersensitivity to serlopitant or any of its components
• Currently pregnant or male partner of pregnant female
• Females of childbearing potential who are unable or unwilling to use adequate contraception or who are breast feeding
• Current smoker or individuals who have given up smoking within the past 12 months
• FEV1/FVC < 60%
• Body mass index (BMI) <18 kg/m2 or ≥ 40 kg/m2 at Screening
• History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit (Day 0)
• History of cystic fibrosis
• History of opioid use within 1 week of the Baseline Visit (Day 0)
• Requiring concomitant therapy with prohibited medications
• Treatment with biologic therapies within 8 weeks or 5 half-lives prior to the Baseline Visit (Day 0), whichever is longer
• Treatment with strong CYP3A4 inhibitors within 4 weeks prior to the Baseline Visit (Day 0)
• Treatment with any investigational therapy within 4 weeks (investigational biologic therapies within 8 weeks) prior to the Baseline Visit (Day 0)
• Serum creatinine, total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x the upper limit of normal (ULN) during screening
• Positive test for any drug of abuse
• History of malignancy within 5 years prior to the Baseline Visit (Day 0), with the exception of completely treated and non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin
• Any known psychiatric diagnosis meeting DSM-5 criteria which may confound the assessment of serlopitant safety or efficacy, or interfere with the subject's ability to comply with protocol-mandated activities, within 3 years prior to randomization. Examples of such DSM-5 diagnoses include but are not limited to major depressive disorder, bipolar disorder, schizophrenia, psychotic disorder, intellectual disability, severe alcohol use disorder.
• Known active hepatitis infection
• Known history of human immunodeficiency virus (HIV) infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5 mg Serlopitant Tablets; Serlopitant Tablets	Drug: 5 mg Serlopitant Tablets; Serlopitant Tablets; Other Names: VPD-737
Placebo Comparator: Matching Placebo Tablets; Placebo Tablets	Drug: Matching Placebo Tablets; Placebo Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 24-hour Objective Cough Frequency (Log Normalized Percent Change Relative to Placebo)	Change in 24-hour objective cough frequency is total number of cough events during the monitoring period (24-hour interval)/24 (Total duration (in hours) for the monitoring period) which is captured through sound recordings by a custom-built digital recording device (VitaloJAK, Vitalograph, Ltd).	from Baseline to Day 84

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Awake Objective Cough Frequency	Awake cough frequency = (total number of cough events during the monitoring period (24-hour interval) the subject is awake)/(Total duration (in hours) for the monitoring period the subject is awake) which is captured by a custom-built digital recording device (VitaloJAK, Vitalograph, Ltd).	from Baseline to Day 84
Percentage of Participants With ≥ 30% Reduction in 24-hour Objective Cough Frequency	The percentage of participants with ≥ 30% of reduction from baseline in 24-hour cough frequency is the number of participants with ≤-30% change in 24-hour cough frequency divided by the total number of participants with available data. This data is captured by a custom-built digital recording device (VitaloJAK, Vitalograph, Ltd).	from Baseline to Day 84
Percentage of Participants With ≥30% Reduction in Awake Objective Cough Frequency	The percentage of participants with ≥ 30% of reduction from baseline in the awake cough frequency is the number of participants with ≤30% change in awake cough frequency divided by the total number of participants with available data. This data is captured by a custom-built digital recording device (VitaloJAK, Vitalograph, Ltd).	from Baseline to Day 84
Change From Baseline in Cough Severity Visual Analog Scale (VAS)	Visual Analog Scale (VAS) 101-point scale ranging from 0 (no cough) to 100 (worst cough). A higher score corresponds to higher cough severity.	from Baseline to Day 84

Collaborators and Investigators

• Sponsor: Vyne Therapeutics Inc.
• Investigators: Principal Investigator: Jacky Smith, University of Manchester, United Kingdom

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2017
• Primary Completion (Actual): August 15, 2018
• Study Completion (Actual): September 6, 2018

Study Registration Dates

• First Submitted: September 11, 2017
• First Submitted That Met QC Criteria: September 12, 2017
• First Posted (Actual): September 14, 2017

Study Record Updates

• Last Update Posted (Actual): May 20, 2021
• Last Update Submitted That Met QC Criteria: May 18, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurokinin-1 Receptor Antagonists; Serlopitant
• Other Study ID Numbers: MTI-110; 2017-003250-16 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No