Dextromethorphan Pediatric Acute Cough Study (CHPA DXM)

A PLACEBO-CONTROLLED, DOUBLE-BLIND, RANDOMIZED, PARALLEL GROUP PILOT STUDY TO EVALUATE THE EFFICACY OF DEXTROMETHORPHAN HYDROBROMIDE ON ACUTE COUGH IN A PEDIATRIC POPULATION

This is a placebo-controlled, double-blind, randomized, parallel group pilot study in approximately 150 subjects to evaluate the efficacy of dextromethorphan hydrobromide (DXM) on acute cough in a pediatric population. Subjects will be otherwise healthy males and females aged 6-11 inclusive who are experiencing acute cough as a symptom of common cold or upper respiratory tract infection. Subjects must have had onset of symptoms within 3 days of screening and qualify based on physical exam and symptom questionnaire. Eligible subjects will be given a single-blind placebo, and fitted with a cough counting device for a 2 hour run-in period. Qualifying subjects will be stratified by age and then randomized to either DXM or placebo in a 1:1 ratio and fitted with the cough recording device for the first 24 hours of treatment. Subjects will receive approximately 9 doses of investigational product over the course of the 4 day study and will complete patient reported outcome questions before the morning and afternoon doses. Subjects will return to the study site on Day 2 to remove the cough recorder and on Day 4 (+ 2 days) to complete the final visit. A review of any reported adverse events will also be completed.

Study Overview

• Status: Terminated
• Conditions: Cough
• Intervention / Treatment: Drug: Dextromethorphan Hydrobromide; Device: Cough recording device; Drug: Placebo

Detailed Description

This is a placebo-controlled, double-blind, randomized, parallel group pilot study in approximately 150 subjects to evaluate the efficacy of dextromethorphan hydrobromide DXM) on acute cough in a pediatric population. Subjects will be otherwise healthy males and females aged 6-11 inclusive who are experiencing acute cough as a symptom of common cold or upper respiratory tract infection. Subjects must have had onset of symptoms within 3 days of screening and qualify based on physical exam and symptom questionnaire. Eligible subjects will be given a single-blind placebo, and fitted with a cough counting device for a 2 hour run-in period. Qualifying subjects will be stratified by age and then randomized to either DXM or placebo in a 1:1 ratio and fitted with the cough recording device for the first 24 hours of treatment. Subjects will receive approximately 9 doses of investigational product over the course of the 4 day study and will complete patient reported outcome questions before the morning and afternoon doses. Subjects will return to the study site on Day 2 to remove the cough recorder and Day 4 (+2 days) to complete the final visit. A review of any reported adverse events will also be completed. Validated Patient Reported Outcomes (PRO) used in the study include morning cough assessment, afternoon cough assessment, Child Global Question, and Child Cold Symptom Checklist

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Orlando, Florida, United States, 32806
      • Clinical Associates of Orlando LLC
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Elite Clinical Trials LLLP
    • Meridian, Idaho, United States, 83642
      • Advanced Clinical Research
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Kentucky Pediatric/Adult Research
    • Louisville, Kentucky, United States, 40243
      • All Children Pediatrics
    • Louisville, Kentucky, United States, 40291
      • Bluegrass Clinical Research, Inc
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • MedPharmics, LLC
  • Nebraska
    • Lincoln, Nebraska, United States, 68504
      • Midwest Children's Health Research Institute
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research LLC
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research, Inc
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Associates
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Pediatric Associates
    • Orangeburg, South Carolina, United States, 29118
      • Carolina Ear, Nose & Throat Clinic/CENTRI Inc.
  • South Dakota
    • Dakota Dunes, South Dakota, United States, 57049
      • Meridian Clinical Research, LLC
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Ventavia Research Group, LLC
    • Fort Worth, Texas, United States, 76104
      • Texas Health Care, PLLC
  • Utah
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Generally healthy male or female children/adolescents ages 6 to 11 years, inclusive.
• Subject has an acute cough and other symptoms consistent with a common cold/acute upper respiratory tract infection (URTI) diagnosis as deemed by the investigator or qualified designee based on findings from medical history review, full physical examination and vital signs.
• The onset of symptoms must be no more than 3 days prior to Visit 1, as determined by the subject or parent/legally acceptable representative.
• Qualifying response on the Child Cold Symptom Checklist.
• Parent/legally acceptable representative, and subject agrees the subject will not use any other cough or cold treatments during the study.

Exclusion Criteria:

• A subchronic, or chronic cough due to any condition other than an URTI or common cold as established by the investigator, nurse practitioner, or physician's assistant, in accordance with the American College of Chest Physicians' (ACCP) Guidelines for Diagnosis and Management of Cough. Special attention should be paid to highly prevalent conditions commonly presenting with cough such as asthma, rhinitis, or gastroesophageal reflux disease (GERD).
• Symptoms of runny nose, stuffy nose, sore throat, or sneezing due to any condition other than URTI or common cold (eg, seasonal or perennial allergic rhinitis, sinusitis, strep throat, vasomotor rhinitis, etc.) as established by the investigator.
• An acute cough that occurs with excessive phlegm (mucus) or is chronic such as occurs with smoking, asthma, bronchitis, allergies, or a gastroesophageal condition (eg, acid reflux and GERD) or history of such a cough.
• Clinical features of a complication of the common cold during the physical examination at screening (eg, otitis media, sinusitis, or pneumonia) with or without the need for systematic antibiotics.
• Pneumonia (active or with a symptom-free period of <30 days), asthma (active or with a symptom-free period of <1 year), or other significant pulmonary diseases.
• Fever greater than 39ºC (102ºF oral temperature) at the time of screening if, in the judgment of the investigator, the individual is too ill to participate in the study or the fever is due to reasons other than URTI.
• Signs of dehydration (as may be due to vomiting, diarrhea, or lack of fluid intake) during the physical examination at screening.
• Diabetes or hypoglycemic disorders.
• Known contraindications to the investigational product or acetaminophen (APAP).
• Sitting blood pressure reading at or above the limits as documented in the protocol.
• Obstructive sleep apnea caused by enlarged tonsils and adenoids, low muscle tone, or allergies.
• History of known or suspected allergy or hypersensitivity to dextromethorphan (DXM) or APAP, or any of the non medicinal ingredients contained in the single-blind confection, double-blind investigational products, or APAP.
• History of taking any of the specified prohibited medications or products within the corresponding washout periods prior to taking the first dose of investigational product.
• History of taking a medication that is sedating within the past 24 hours prior to screening (eg sedatives, hypnotics, tranquilizers, anticonvulsants, benzodiazepines, and clonidine).
• Subject has a sibling contemporaneously participating in this study.

Randomization Criteria:

• Subjects must complete the 2 hour ambulatory cough counting baseline run-in recording period and must return to the study site for randomization at least 2 hours after the recording started.
• Subjects whose equipment failed, preventing collection of cough count data for at least 2 hours during the Baseline Run-in Period, or those who took off the device during this period will be excluded from further study participation.
• Subjects who do not return to the study site (before 3:30 pm) in time for the afternoon dose will not be randomized.
• Qualifying response on Child Global Question

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dextromethorphan Hydrobromide; 15 mg/ 10 mL: 10 mL of Dextromethorphan Hydrobromide	Drug: Dextromethorphan Hydrobromide; 15 mg/ 10 mL: 10 mL of Dextromethorphan Hydrobromide; Other Names: DXM; Device: Cough recording device; FDA approved device validated for use in adults and children; Other Names: VitaloJAK
Placebo Comparator: Placebo; 10 mL of Placebo	Device: Cough recording device; FDA approved device validated for use in adults and children; Other Names: VitaloJAK; Drug: Placebo; 10 mL Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean of Total Cough Counts: Over 24 Hours Post-First Dose on Day 1	Total cough count was collected by the cough recording device VitaloJAKTM in an ambulatory setting. The VitaloJAKTM device recorded continuous digital audio obtained through both a lapel microphone clipped to the participant's clothing at the neck or upper chest level, and a chest wall sensor attached to the participant's chest at the top of the sternum. Data was captured on a data card and the vitalograph analyst evaluated cough counts.	Over for 24 hours post-first dose on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean of Total Cough Counts: Between Dose 1 to Dose 2 on Day 1	Total cough count was collected by the cough recording device VitaloJAKTM in an ambulatory setting. The VitaloJAKTM device recorded continuous digital audio obtained through both a lapel microphone clipped to the participant's clothing at the neck or upper chest level, and a chest wall sensor attached to the participant's chest at the top of the sternum. Data was captured on a data card and the vitalograph analyst evaluated cough counts.	Between Dose 1 to Dose 2 on Day 1
Mean of Total Cough Counts: Between Dose 2 on Day 1 to Dose 3 on Day 2	Total cough count was collected by the cough recording device VitaloJAKTM in an ambulatory setting. The VitaloJAKTM device recorded continuous digital audio obtained through both a lapel microphone clipped to the participant's clothing at the neck or upper chest level, and a chest wall sensor attached to the participant's chest at the top of the sternum. Data was captured on a data card and the vitalograph analyst evaluated cough counts.	Between Dose 2 on Day 1 to Dose 3 on Day 2 (second dose of Day 1 to first dose of Day 2)
Mean of Total Cough Counts: Between Dose 3 to Dose 4 on Day 2	Total cough count was collected by the cough recording device VitaloJAKTM in an ambulatory setting. The VitaloJAKTM device recorded continuous digital audio obtained through both a lapel microphone clipped to the participant's clothing at the neck or upper chest level, and a chest wall sensor attached to the participant's chest at the top of the sternum. Data was captured on a data card and the vitalograph analyst evaluated cough counts.	Between Dose 3 to Dose 4 on Day 2 (between first and second dose of Day 2)
Mean of Total Cough Counts: Between Dose 1 to Dose 2 on Day 1, and Between Dose 3 to Dose 4 on Day 2	Total cough count was collected by the cough recording device VitaloJAKTM in an ambulatory setting. The VitaloJAKTM device recorded continuous digital audio obtained through both a lapel microphone clipped to the participant's clothing at the neck or upper chest level, and a chest wall sensor attached to the participant's chest at the top of the sternum. Data was captured on a data card and the vitalograph analyst evaluated cough counts. In this outcome measure, as planned combined data is reported for first dosing interval (Dose 1 to Dose 2) on Day 1 and first dosing interval (Dose 3 to Dose 4) on Day 2.	Duration between Dose 1 to Dose 2 on Day 1 (between first and second dose of Day 1) plus duration between Dose 3 to Dose 4 on Day 2 (between first and second dose of Day 2)
Mean of Total Cough Time Accumulated Over a 24-Hour Period Post-First Dose on Day 1	Time (in seconds) accumulated over a 24-hour period when cough events occurred was collected by the cough recording device VitaloJAKTM in an ambulatory setting. The VitaloJAKTM device recorded continuous digital audio obtained through both a lapel microphone clipped to the participant's clothing at the neck or upper chest level, and a chest wall sensor attached to the participant's chest at the top of the sternum. Data was captured on a data card and the vitalograph analyst evaluated total cough time accumulated.	Over for 24 hours post-first dose on Day 1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Morning Cough Frequency Assessed in Morning at Day 2, 3, and 4	Participants on specified time points were asked to respond to the following question: "from when you woke up this morning until now, how much have you been coughing", on a 5-point scale: 0= not at all, 1= a tiny bit, 2= a little, 3= some and 4= a lot. Higher scores indicated higher frequency of cough in morning time.	Baseline (morning screening visit on Day 1); Within 30 minutes of waking, before morning dose on Days 2, 3, and 4
Change From Baseline in Morning Cough Severity Assessed in Morning at Day 2, 3, and 4	Participants on specified time points were asked to respond to the following question: "how bad is your cough this morning", on a 5-point scale: 0= no cough, 1= a tiny bit bad, 2= a little bad, 3= bad and 4= very bad. Higher scores indicated more severe cough in morning time.	Baseline (morning screening visit on Day 1); Within 30 minutes of waking, before morning dose on Days 2, 3, and 4
Change From Baseline in Impact of Cough on Sleep Assessed in Morning at Day 2, 3, and 4	Participants on specified time points were asked to respond to the following question: "last night in bed, how much did your cough keep you awake", on a 5-point scale: 0= not at all, 1= a tiny bit, 2= a little, 3= some and 4= a lot. Higher scores indicated worse impact of cough on sleep.	Baseline (morning screening visit on Day 1); Within 30 minutes of waking, before morning dose on Days 2, 3, and 4
Change From Baseline in Afternoon Cough Frequency Assessed at Afternoon on Day 2, 3, and 4	Participants on specified time points were asked to respond to the following question: "how much have you been coughing this afternoon" on a 5-point scale: 0= not at all, 1= a tiny bit, 2= a little, 3= some and 4= a lot. Higher scores indicated higher frequency of cough in afternoon time.	Baseline (afternoon visit on Day 1 before first dose); Before the afternoon dose on Day 2, and 3; Anytime in afternoon of Day 4
Change From Baseline in Afternoon Cough Severity Assessed at Afternoon on Day 2, 3, and 4	Participants on specified time points were asked to respond to the following question: "how bad is your cough this afternoon" on a 5-point scale: 0= no cough, 1= a tiny bit bad, 2= a little bad, 3= bad and 4= very bad. Higher scores indicated more severe cough in afternoon time.	Baseline (afternoon visit on Day 1 before first dose); Before the afternoon dose on Day 2, and 3; Anytime in afternoon of Day 4
Change From Baseline in Child Global Question Assessed at Afternoon on Day 2, 3, and 4	Participants on specified time points were asked to respond to the following question: "how bad is your cold today", on a 5-point scale; 0= no cold, 1= a tiny bit bad, 2= a little bad, 3= bad, and 4= very bad. Higher scores indicated worse cold.	Baseline (afternoon visit on Day 1 before first dose); Before the afternoon dose on Day 2, and 3; Anytime in afternoon of Day 4
Pediatric Global Assessment of Satisfaction With Study Medication: By Participant, and Caregiver	Participants at the end of the study were asked to respond to the following question: "How would you rate the study medication for taking away your cough?" on a 7-point scale: 0= excellent, 1= very good, 2= good, 3= fair, 4= poor, 5= very poor, and 6= terrible. Higher scores indicated poorer satisfaction with study medication. Within 20 minutes after participants completed the assessment parents/legally acceptable representative were asked to respond to the question: "How would you rate the study medication for taking away your child's cough?" on a 7-point scale: 0= excellent, 1= very good, 2= good, 3= fair, 4= poor, 5= very poor, and 6= terrible. Higher scores indicated poorer satisfaction with study medication.	For participants: at the end of the study on Day 4; For parents/legally acceptable representatives: within 20 minutes after participant completed assessment at the end of the study on Day 4

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2016
• Primary Completion (Actual): March 19, 2020
• Study Completion (Actual): March 19, 2020

Study Registration Dates

• First Submitted: January 7, 2016
• First Submitted That Met QC Criteria: January 7, 2016
• First Posted (Estimate): January 8, 2016

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: cough, acute cough, pediatric, Dextromethorphan Hydrobromide, antitussive, ambulatory cough recording device
• 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; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Respiratory System Agents; Antitussive Agents; Dextromethorphan
• Other Study ID Numbers: A6531002; CHPA DXM (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.