CHPA DXM: Dextromethorphan Pediatric Acute Cough Study

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02651116
• Collaborator: (none)
• Enrollment: 131
• Locations: 18
• Arms: 2
• Actual Duration (Months): 48.8
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cough	Drug: Dextromethorphan Hydrobromide; Drug: Placebo; Device: Cough recording device	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A PLACEBO-CONTROLLED, DOUBLE-BLIND, RANDOMIZED, PARALLEL GROUP PILOT STUDY TO EVALUATE THE EFFICACY OF DEXTROMETHORPHAN HYDROBROMIDE ON ACUTE COUGH IN A PEDIATRIC POPULATION
• Actual Study Start Date: Feb 25, 2016
• Actual Primary Completion Date: Mar 19, 2020
• Actual Study Completion Date: Mar 19, 2020

Arms and Interventions

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	Drug: Placebo; 10 mL Placebo; Device: Cough recording device; FDA approved device validated for use in adults and children; Other Names: VitaloJAK

Outcome Measures

Primary Outcome Measures

1. Mean of Total Cough Counts: Over 24 Hours Post-First Dose on Day 1 [Over for 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.

Secondary Outcome Measures

1. Mean of Total Cough Counts: Between Dose 1 to Dose 2 on Day 1 [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.

2. Mean of Total Cough Counts: Between Dose 2 on Day 1 to Dose 3 on Day 2 [Between Dose 2 on Day 1 to Dose 3 on Day 2 (second dose of Day 1 to first dose of 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.

3. Mean of Total Cough Counts: Between Dose 3 to Dose 4 on Day 2 [Between Dose 3 to Dose 4 on Day 2 (between first and second dose of 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.

4. Mean of Total Cough Counts: Between Dose 1 to Dose 2 on Day 1, and Between 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)]

   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.

5. Mean of Total Cough Time Accumulated Over a 24-Hour Period Post-First Dose on Day 1 [Over for 24 hours 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.

Other Outcome Measures

1. Change From Baseline in Morning Cough Frequency Assessed in Morning at Day 2, 3, and 4 [Baseline (morning screening visit on Day 1); Within 30 minutes of waking, before morning dose on Days 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.

2. Change From Baseline in Morning Cough Severity Assessed in Morning at Day 2, 3, and 4 [Baseline (morning screening visit on Day 1); Within 30 minutes of waking, before morning dose on Days 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.

3. Change From Baseline in Impact of Cough on Sleep Assessed in Morning at Day 2, 3, and 4 [Baseline (morning screening visit on Day 1); Within 30 minutes of waking, before morning dose on Days 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.

4. Change From Baseline in Afternoon Cough Frequency Assessed at Afternoon on Day 2, 3, and 4 [Baseline (afternoon visit on Day 1 before first dose); Before the afternoon dose on Day 2, and 3; Anytime in afternoon of Day 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.

5. Change From Baseline in Afternoon Cough Severity Assessed at Afternoon on Day 2, 3, and 4 [Baseline (afternoon visit on Day 1 before first dose); Before the afternoon dose on Day 2, and 3; Anytime in afternoon of Day 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.

6. Change From Baseline in Child Global Question Assessed at Afternoon on Day 2, 3, and 4 [Baseline (afternoon visit on Day 1 before first dose); Before the afternoon dose on Day 2, and 3; Anytime in afternoon of Day 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.

7. Pediatric Global Assessment of Satisfaction With Study Medication: By Participant, and Caregiver [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]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Avail Clinical Research, LLC	DeLand	Florida	United States	32720
2	Clinical Associates of Orlando LLC	Orlando	Florida	United States	32806
3	Elite Clinical Trials LLLP	Blackfoot	Idaho	United States	83221
4	Advanced Clinical Research	Meridian	Idaho	United States	83642
5	Kentucky Pediatric/Adult Research	Bardstown	Kentucky	United States	40004
6	All Children Pediatrics	Louisville	Kentucky	United States	40243
7	Bluegrass Clinical Research, Inc	Louisville	Kentucky	United States	40291
8	MedPharmics, LLC	Metairie	Louisiana	United States	70006
9	Midwest Children's Health Research Institute	Lincoln	Nebraska	United States	68504
10	Meridian Clinical Research LLC	Omaha	Nebraska	United States	68134
11	Rapid Medical Research, Inc	Cleveland	Ohio	United States	44122
12	Coastal Pediatric Associates	Charleston	South Carolina	United States	29414
13	Coastal Pediatric Associates	Mount Pleasant	South Carolina	United States	29464
14	Carolina Ear, Nose & Throat Clinic/CENTRI Inc.	Orangeburg	South Carolina	United States	29118
15	Meridian Clinical Research, LLC	Dakota Dunes	South Dakota	United States	57049
16	Texas Health Care, PLLC	Fort Worth	Texas	United States	76104
17	Ventavia Research Group, LLC	Fort Worth	Texas	United States	76104
18	Advanced Clinical Research	West Jordan	Utah	United States	84088

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

• Study Protocol - Jul 18, 2018
• Statistical Analysis Plan - Aug 23, 2018

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02651116
• Other Study ID Numbers: A6531002; CHPA DXM
• First Posted: Jan 8, 2016
• Last Update Posted: Apr 28, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: cough, acute cough, pediatric, Dextromethorphan Hydrobromide, antitussive, ambulatory cough recording device
• Additional relevant MeSH terms: Cough; Dextromethorphan

Study Results

Participant Flow

Recruitment Details	Study was conducted in the United States from 25 February 2016 to 19 March 2020.
Pre-assignment Detail	There was a run-in period of 2 hours where participants were administered 10 milliliter (mL) of non-medicinal liquid oral confection for once, and fitted with cough counting device VitaloJAKTM. Eligible participants who completed run-in period, were qualified for randomization to either dextromethorphan hydrobromide (DXM HBr) or placebo in a 4 day treatment period.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 milligram [mg] per 10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Period Title: Overall Study
STARTED	68	63
Treated	68	63
COMPLETED	67	62
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo	Total
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Total of all reporting groups
Overall Participants	68	63	131
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	8.3 (1.57)	8.0 (1.73)	8.2 (1.65)
Sex: Female, Male (Count of Participants)
Female	35 51.5%	32 50.8%	67 51.1%
Male	33 48.5%	31 49.2%	64 48.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 5.9%	7 11.1%	11 8.4%
Not Hispanic or Latino	64 94.1%	56 88.9%	120 91.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	24 35.3%	22 34.9%	46 35.1%
White	40 58.8%	39 61.9%	79 60.3%
More than one race	4 5.9%	2 3.2%	6 4.6%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Mean of Total Cough Counts: Over 24 Hours Post-First Dose on Day 1
Description	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.
Time Frame	Over for 24 hours post-first dose on Day 1

Outcome Measure Data

Analysis Population Description

The full analysis set included all participants who were randomized, took Dose 1, had a valid baseline cough count assessment, and provided any post-dosing efficacy data.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Measure Participants	67	61
Mean (Standard Deviation) [cough counts]	457.1 (367.21)	676.8 (814.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	Estimated rate ratio (ratio of rate of cough counts per 24 hours for DXM HBr to placebo), and corresponding 95% confidence interval (CI) for DXM HBr versus placebo was obtained from negative binomial model with treatment, study site (pooled), age group, and log-transformed baseline average cough count per hour as factors, with logarithm of the time over which the cough count was evaluated as the offset parameter.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0449
	Comments	P-Value less than or equal to (<=) 0.05 level was considered significantly better and P-Value lying between 0.05 less than (<) p<=0.1 level was considered marginally significantly better.
	Method	Negative Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.7899
	Confidence Interval	(2-Sided) 95%; 0.6273 to 0.9947
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0929
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	P-value was obtained from the negative binomial model with treatment, study site (pooled), age group, log-transformed baseline average cough count per hour (based on Baseline Run-in Period) as factors, with interaction term of treatment by age group, and logarithm of the time over which the cough count was evaluated as the offset parameter.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6293
	Comments	P-value is for interaction term of treatment by age group. P-value <=0.10 was considered significant for interaction terms.
	Method	Negative Binomial Regression
	Comments

2. Secondary Outcome

Title	Mean of Total Cough Counts: Between Dose 1 to Dose 2 on Day 1
Description	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.
Time Frame	Between Dose 1 to Dose 2 on Day 1

Outcome Measure Data

Analysis Population Description

The full analysis set included all participants who were randomized, took Dose 1, had a valid baseline cough count assessment, and provided any post-dosing efficacy data. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Measure Participants	66	61
Mean (Standard Deviation) [cough counts]	32.73 (30.597)	47.03 (57.729)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	Estimated rate ratio (ratio of rate of cough counts per specified duration for DXM HBr to placebo, used in evaluation of this outcome measure), and corresponding 95% CI for DXM HBr versus placebo was obtained from negative binomial model with treatment, study site (pooled), age group, and log-transformed baseline average cough count per hour as factors, with logarithm of the time over which the cough count was evaluated as the offset parameter.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0552
	Comments	P-Value <=0.05 level was considered significantly better and P-Value lying between 0.05<p<=0.1 level was considered marginally significantly better.
	Method	Negative Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.8048
	Confidence Interval	(2-Sided) 95%; 0.6446 to 1.0049
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0912
	Estimation Comments

3. Secondary Outcome

Title	Mean of Total Cough Counts: Between Dose 2 on Day 1 to Dose 3 on Day 2
Description	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.
Time Frame	Between Dose 2 on Day 1 to Dose 3 on Day 2 (second dose of Day 1 to first dose of Day 2)

Outcome Measure Data

Analysis Population Description

The full analysis set included all participants who were randomized, took Dose 1, had a valid baseline cough count assessment, and provided any post-dosing efficacy data. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Measure Participants	65	61
Mean (Standard Deviation) [cough counts]	9.70 (8.877)	11.44 (13.193)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	Estimated rate ratio (ratio of rate of cough counts per specified duration for DXM HBr to placebo, used in evaluation of this outcome measure), and corresponding 95% CI for DXM HBr versus placebo was obtained from negative binomial model with treatment, study site (pooled), age group, and log-transformed baseline average cough count per hour as factors, with logarithm of the time over which the cough count was evaluated as the offset parameter.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7684
	Comments	P-Value <=0.05 level was considered significantly better and P-Value lying between 0.05<p<=0.1 level was considered marginally significantly better.
	Method	Negative Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.9551
	Confidence Interval	(2-Sided) 95%; 0.7032 to 1.2971
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1491
	Estimation Comments

4. Secondary Outcome

Title	Mean of Total Cough Counts: Between Dose 3 to Dose 4 on Day 2
Description	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.
Time Frame	Between Dose 3 to Dose 4 on Day 2 (between first and second dose of Day 2)

Outcome Measure Data

Analysis Population Description

The full analysis set included all participants who were randomized, took Dose 1, had a valid baseline cough count assessment, and provided any post-dosing efficacy data. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Measure Participants	65	60
Mean (Standard Deviation) [cough counts]	19.32 (16.752)	33.62 (47.709)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	Estimated rate ratio (ratio of rate of cough counts per specified duration for DXM HBr to placebo, used in evaluation of this outcome measure), and corresponding 95% CI for DXM HBr versus placebo was obtained from negative binomial model with treatment, study site (pooled), age group, and log-transformed baseline average cough count per hour as factors, with logarithm of the time over which the cough count was evaluated as the offset parameter.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0220
	Comments	P-Value <=0.05 level was considered significantly better and P-Value lying between 0.05<p<=0.1 level was considered marginally significantly better.
	Method	Negative Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.7014
	Confidence Interval	(2-Sided) 95%; 0.5178 to 0.9500
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1086
	Estimation Comments

5. Secondary Outcome

Title	Mean of Total Cough Counts: Between Dose 1 to Dose 2 on Day 1, and Between Dose 3 to Dose 4 on Day 2
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

The full analysis set included all participants who were randomized, took Dose 1, had a valid baseline cough count assessment, and provided any post-dosing efficacy data. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Measure Participants	66	61
Mean (Standard Deviation) [cough counts]	26.13 (21.498)	40.39 (49.896)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	Estimated rate ratio (ratio of rate of cough counts per specified duration for DXM HBr to placebo, used in evaluation of this outcome measure), and corresponding 95% CI for DXM HBr versus placebo was obtained from negative binomial model with treatment, study site (pooled), age group, and log-transformed baseline average cough count per hour as factors, with logarithm of the time over which the cough count was evaluated as the offset parameter.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0098
	Comments	P-Value <=0.05 level was considered significantly better and P-Value lying between 0.05<p<=0.1 level was considered marginally significantly better.
	Method	Negative Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.7454
	Confidence Interval	(2-Sided) 95%; 0.5964 to 0.9316
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0848
	Estimation Comments

6. Secondary Outcome

Title	Mean of Total Cough Time Accumulated Over a 24-Hour Period Post-First Dose on Day 1
Description	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.
Time Frame	Over for 24 hours post-first dose on Day 1

Outcome Measure Data

Analysis Population Description

The full analysis set included all participants who were randomized, took Dose 1, had a valid baseline cough count assessment, and provided any post-dosing efficacy data.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Measure Participants	67	61
Mean (Standard Deviation) [seconds]	350.5 (268.95)	502.7 (566.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	Analysis of covariance (ANCOVA) model contained treatment, study site (pooled), log-transformed baseline cough time and age group terms as factors.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0977
	Comments	P-Value <=0.05 level was considered significantly better and P-Value lying between 0.05<p<=0.1 level was considered marginally significantly better.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in least squares mean
	Estimated Value	-0.2210
	Confidence Interval	(2-Sided) 95%; -0.4831 to 0.0411
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1324
	Estimation Comments

7. Other Pre-specified Outcome

Title	Change From Baseline in Morning Cough Frequency Assessed in Morning at Day 2, 3, and 4
Description	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.
Time Frame	Baseline (morning screening visit on Day 1); Within 30 minutes of waking, before morning dose on Days 2, 3, and 4

Outcome Measure Data

Analysis Population Description

The full analysis set included all participants who were randomized, took Dose 1, had a valid baseline cough count assessment, and provided any post-dosing efficacy data. Here 'number analyzed' signifies participants with available data for each specified category.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Measure Participants	67	61
Baseline	3.4 (0.65)	3.3 (0.63)
Change at Day 2	-1.2 (1.30)	-0.7 (1.15)
Change at Day 3	-1.5 (1.15)	-1.1 (1.38)
Change at Day 4	-2.0 (1.20)	-1.8 (1.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	Analysis of variance (ANOVA) model contained treatment, study site (pooled), the corresponding morning baseline cough frequency by participant, and age group included in the model. The statistical analysis was performed on the composite for all categories.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0191
	Comments	P-Value <=0.05 level was considered significantly better and P-Value lying between 0.05<p<=0.1 level was considered marginally significantly better.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in least squares mean
	Estimated Value	-0.2881
	Confidence Interval	(2-Sided) 95%; -0.5287 to -0.0475
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1224
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	ANOVA model contained treatment, study site (pooled), screening assessment by participant, interaction of treatment by age group and age group included in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8355
	Comments	P-value is for interaction term of treatment by age group. P-value <=0.10 was considered significant for interaction terms.
	Method	ANOVA
	Comments

8. Other Pre-specified Outcome

Title	Change From Baseline in Morning Cough Severity Assessed in Morning at Day 2, 3, and 4
Description	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.
Time Frame	Baseline (morning screening visit on Day 1); Within 30 minutes of waking, before morning dose on Days 2, 3, and 4

Outcome Measure Data

Analysis Population Description

The full analysis set included all participants who were randomized, took Dose 1, had a valid baseline cough count assessment, and provided any post-dosing efficacy data. Here 'number analyzed' signifies participants with available data for each specified category.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Measure Participants	67	61
Baseline	3.1 (0.54)	3.1 (0.60)
Change at Day 2	-1.1 (0.89)	-0.6 (1.19)
Change at Day 3	-1.4 (0.96)	-1.3 (1.22)
Change at Day 4	-1.9 (1.10)	-1.8 (1.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	ANOVA model contained treatment, study site (pooled), the corresponding morning baseline cough severity by participant, and age group included in the model. The statistical analysis was performed on the composite for all categories.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0049
	Comments	P-Value <=0.05 level was considered significantly better and P-Value lying between 0.05<p<=0.1 level was considered marginally significantly better.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in least squares mean
	Estimated Value	-0.3128
	Confidence Interval	(2-Sided) 95%; -0.5299 to -0.0956
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1104
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	ANOVA model contained treatment, study site (pooled), screening assessment by participant, interaction of treatment by age group and age group included in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8413
	Comments	P-value is for interaction term of treatment by age group. P-value <=0.10 was considered significant for interaction terms.
	Method	ANOVA
	Comments

9. Other Pre-specified Outcome

Title	Change From Baseline in Impact of Cough on Sleep Assessed in Morning at Day 2, 3, and 4
Description	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.
Time Frame	Baseline (morning screening visit on Day 1); Within 30 minutes of waking, before morning dose on Days 2, 3, and 4

Outcome Measure Data

Analysis Population Description

The full analysis set included all participants who were randomized, took Dose 1, had a valid baseline cough count assessment, and provided any post-dosing efficacy data. Here 'number analyzed' signifies participants with available data for each specified category.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Measure Participants	67	61
Baseline	2.8 (1.15)	3.0 (1.19)
Change at Day 2	-0.8 (1.56)	-0.7 (1.45)
Change at Day 3	-1.3 (1.59)	-1.4 (1.67)
Change at Day 4	-1.8 (1.57)	-1.9 (1.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	ANOVA model contained treatment, study site (pooled), the corresponding morning baseline impact on sleep by participant, and age group included in the model. The statistical analysis was performed on the composite for all categories.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2679
	Comments	P-Value <=0.05 level was considered significantly better and P-Value lying between 0.05<p<=0.1 level was considered marginally significantly better.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in least squares mean
	Estimated Value	-0.1483
	Confidence Interval	(2-Sided) 95%; -0.4112 to 0.1146
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1337
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	ANOVA model contained treatment, study site (pooled), screening assessment by participant, interaction of treatment by age group and age group included in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2882
	Comments	P-value is for interaction term of treatment by age group. P-value <=0.10 was considered significant for interaction terms.
	Method	ANOVA
	Comments

10. Other Pre-specified Outcome

Title	Change From Baseline in Afternoon Cough Frequency Assessed at Afternoon on Day 2, 3, and 4
Description	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.
Time Frame	Baseline (afternoon visit on Day 1 before first dose); Before the afternoon dose on Day 2, and 3; Anytime in afternoon of Day 4

Outcome Measure Data

Analysis Population Description

The full analysis set included all participants who were randomized, took Dose 1, had a valid baseline cough count assessment, and provided any post-dosing efficacy data. Here 'number analyzed' signifies participants with available data for each specified category.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Measure Participants	67	61
Baseline	3.2 (0.80)	3.4 (0.73)
Change at Day 2	-0.7 (1.25)	-0.6 (1.06)
Change at Day 3	-1.5 (1.30)	-1.4 (1.27)
Change at Day 4	-1.9 (1.22)	-1.8 (1.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	ANOVA model contained treatment, study site (pooled), the corresponding afternoon baseline cough frequency by participant, and age group included in the model. The statistical analysis was performed on the composite for all categories.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0242
	Comments	P-Value <=0.05 level was considered significantly better and P-Value lying between 0.05<p<=0.1 level was considered marginally significantly better.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in least squares mean
	Estimated Value	-0.2812
	Confidence Interval	(2-Sided) 95%; -0.5255 to -0.0369
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1242
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	ANOVA model contained treatment, study site (pooled), afternoon baseline assessment by participant, interaction of treatment by age group and age group included in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2892
	Comments	P-value is for interaction term of treatment by age group. P-value <=0.10 was considered significant for interaction terms.
	Method	ANOVA
	Comments

11. Other Pre-specified Outcome

Title	Change From Baseline in Afternoon Cough Severity Assessed at Afternoon on Day 2, 3, and 4
Description	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.
Time Frame	Baseline (afternoon visit on Day 1 before first dose); Before the afternoon dose on Day 2, and 3; Anytime in afternoon of Day 4

Outcome Measure Data

Analysis Population Description

The full analysis set included all participants who were randomized, took Dose 1, had a valid baseline cough count assessment, and provided any post-dosing efficacy data. Here 'number analyzed' signifies participants with available data for each specified category.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Measure Participants	67	61
Baseline	2.8 (0.83)	3.1 (0.84)
Change at Day 2	-0.7 (1.16)	-0.6 (0.98)
Change at Day 3	-1.4 (1.15)	-1.4 (1.24)
Change at Day 4	-1.7 (1.08)	-1.6 (1.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	ANOVA model contained treatment, study site (pooled), the corresponding afternoon baseline cough severity by participant, and age group included in the model. The statistical analysis was performed on the composite for all categories.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0063
	Comments	P-Value <=0.05 level was considered significantly better and P-Value lying between 0.05<p<=0.1 level was considered marginally significantly better.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in least squares mean
	Estimated Value	-0.3014
	Confidence Interval	(2-Sided) 95%; -0.5170 to -0.0858
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1096
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	ANOVA model contained treatment, study site (pooled), afternoon baseline assessment by participant, interaction of treatment by age group and age group included in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3268
	Comments	P-value is for interaction term of treatment by age group. P-value <=0.10 was considered significant for interaction terms.
	Method	ANOVA
	Comments

12. Other Pre-specified Outcome

Title	Change From Baseline in Child Global Question Assessed at Afternoon on Day 2, 3, and 4
Description	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.
Time Frame	Baseline (afternoon visit on Day 1 before first dose); Before the afternoon dose on Day 2, and 3; Anytime in afternoon of Day 4

Outcome Measure Data

Analysis Population Description

The full analysis set included all participants who were randomized, took Dose 1, had a valid baseline cough count assessment, and provided any post-dosing efficacy data. Here 'number analyzed' signifies participants with available data for each specified category.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Measure Participants	67	61
Baseline	3.2 (0.42)	3.3 (0.46)
Change at Day 2	-1.1 (1.02)	-0.9 (1.01)
Change at Day 3	-1.6 (0.93)	-1.6 (1.13)
Change at Day 4	-2.1 (0.87)	-1.7 (1.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	ANOVA model with treatment, study site (pooled), the baseline assessment in child global question cold assessment by participant and age group included in the model. The statistical analysis was performed on the composite for all categories.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0247
	Comments	P-Value <=0.05 level was considered significantly better and P-Value lying between 0.05<p<=0.1 level was considered marginally significantly better.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in least squares mean
	Estimated Value	-0.2535
	Confidence Interval	(2-Sided) 95%; -0.4745 to -0.0325
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1124
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	ANOVA model with treatment, study site (pooled), baseline assessment by participant, interaction of treatment by age group and age group included in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4093
	Comments	P-value is for interaction term of treatment by age group. P-value <=0.10 was considered significant for interaction terms.
	Method	ANOVA
	Comments

13. Other Pre-specified Outcome

Title	Pediatric Global Assessment of Satisfaction With Study Medication: By Participant, and Caregiver
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The full analysis set included all participants who were randomized, took Dose 1, had a valid baseline cough count assessment, and provided any post-dosing efficacy data. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Dextromethorphan Hydrobromide	Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.	Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
Measure Participants	66	61
By Participant:	1.7 (1.20)	1.6 (1.26)
By Caregiver:	1.8 (1.07)	1.9 (1.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	Participant: ANOVA model with treatment, study site (pooled), and age group included in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5652
	Comments	P-Value <=0.05 level was considered significantly better and P-Value lying between 0.05<p<=0.1 level was considered marginally significantly better.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in least squares mean
	Estimated Value	0.1266
	Confidence Interval	(2-Sided) 95%; -0.3081 to 0.5614
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2196
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	Caregiver: ANOVA model with treatment, study site (pooled), and age group included in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4914
	Comments	P-Value <=0.05 level was considered significantly better and P-Value lying between 0.05<p<=0.1 level was considered marginally significantly better.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in least squares mean
	Estimated Value	-0.1368
	Confidence Interval	(2-Sided) 95%; -0.5292 to 0.2556
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1982
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	Participant: ANOVA model with treatment, study site (pooled), interaction of treatment by age group and age group included in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1029
	Comments	P-value is for interaction term of treatment by age group. P-value <=0.10 was considered significant for interaction terms.
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan Hydrobromide, Placebo
	Comments	Caregiver: ANOVA model with treatment, study site (pooled), interaction of treatment by age group and age group included in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4736
	Comments	P-value is for interaction term of treatment by age group. P-value <=0.10 was considered significant for interaction terms.
	Method	ANOVA
	Comments

Adverse Events

Time Frame	Day 1 up to 14 days after last dose of study medication (up to 18 days)
Adverse Event Reporting Description	Same event may appear as Adverse Event and Serious Adverse Events, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety was evaluated on all participants who received the study drug.
Arm/Group Title	Dextromethorphan Hydrobromide		Placebo
Arm/Group Description	Participants were randomized to receive 9 doses of DXM HBr (15 mg/10 mL) over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of DXM HBr syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of DXM HBr syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of DXM HBr syrup in morning. Participants were followed up for 14 days after last dose of study medication.		Participants were randomized to receive 9 doses of placebo matched to 15 mg/10 mL DXM HBr over the course of 4 day study treatment and were fitted with the cough recording device VitaloJAKTM for the first 24 hours of treatment. On Day 1, participants received a single 10 mL oral dose of placebo syrup each in afternoon and evening. On Day 2 and 3, participants received a single 10 mL oral dose of placebo syrup each in morning, afternoon and evening. On Day 4, participants received a single 10 mL oral dose of placebo syrup in morning. Participants were followed up for 14 days after last dose of study medication.
All Cause Mortality
	Dextromethorphan Hydrobromide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/63 (0%)
Serious Adverse Events
	Dextromethorphan Hydrobromide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/63 (0%)
Other (Not Including Serious) Adverse Events
	Dextromethorphan Hydrobromide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/68 (19.1%)		16/63 (25.4%)
Blood and lymphatic system disorders
Lymphadenopathy	1/68 (1.5%)		1/63 (1.6%)
Ear and labyrinth disorders
Tympanic membrane hyperaemia	1/68 (1.5%)		0/63 (0%)
Gastrointestinal disorders
Lip dry	0/68 (0%)		1/63 (1.6%)
General disorders
Malaise	0/68 (0%)		1/63 (1.6%)
Pain	1/68 (1.5%)		0/63 (0%)
Infections and infestations
Bronchiolitis	0/68 (0%)		1/63 (1.6%)
Influenza	0/68 (0%)		1/63 (1.6%)
Nasopharyngitis	0/68 (0%)		1/63 (1.6%)
Otitis media	0/68 (0%)		2/63 (3.2%)
Otitis media acute	0/68 (0%)		1/63 (1.6%)
Upper respiratory tract infection	0/68 (0%)		1/63 (1.6%)
Urinary tract infection	0/68 (0%)		1/63 (1.6%)
Viral infection	0/68 (0%)		1/63 (1.6%)
Injury, poisoning and procedural complications
Joint injury	0/68 (0%)		1/63 (1.6%)
Nervous system disorders
Headache	1/68 (1.5%)		3/63 (4.8%)
Psychomotor hyperactivity	1/68 (1.5%)		0/63 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/68 (1.5%)		1/63 (1.6%)
Nasal congestion	0/68 (0%)		1/63 (1.6%)
Nasal dryness	0/68 (0%)		1/63 (1.6%)
Nasal mucosal disorder	0/68 (0%)		1/63 (1.6%)
Nasal oedema	0/68 (0%)		1/63 (1.6%)
Nasal turbinate abnormality	3/68 (4.4%)		1/63 (1.6%)
Pharyngeal erythema	1/68 (1.5%)		1/63 (1.6%)
Rhinitis allergic	1/68 (1.5%)		0/63 (0%)
Rhinorrhoea	2/68 (2.9%)		3/63 (4.8%)
Rhonchi	1/68 (1.5%)		0/63 (0%)
Upper-airway cough syndrome	0/68 (0%)		2/63 (3.2%)
Skin and subcutaneous tissue disorders
Dennie-Morgan fold	2/68 (2.9%)		0/63 (0%)
Erythema	0/68 (0%)		1/63 (1.6%)
Photosensitivity reaction	1/68 (1.5%)		0/63 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.