Dextromethorphan Pediatric Acute Cough Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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

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

Conditions
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Cough

Intervention / Treatment
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* Drug: Dextromethorphan Hydrobromide
* Drug: Placebo
* Device: Cough recording device


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cough, acute cough, pediatric, Dextromethorphan Hydrobromide, antitussive, ambulatory cough recording device