Cough
Conditions
Keywords
cough, acute cough, pediatric, Dextromethorphan Hydrobromide, antitussive, ambulatory cough recording device
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.
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
Interventions
15 mg/ 10 mL: 10 mL of Dextromethorphan Hydrobromide
DRUGPlacebo
10 mL Placebo
DEVICECough recording device
FDA approved device validated for use in adults and children
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
Study was conducted in the United States from 25 February 2016 to 19 March 2020.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Dextromethorphan Hydrobromide 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. | 68 |
| Placebo 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. | 63 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | No Longer Willing To Participate In Study | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Dextromethorphan Hydrobromide |
|---|---|---|---|
| Age, Continuous | 8.0 Years STANDARD_DEVIATION 1.73 | 8.2 Years STANDARD_DEVIATION 1.65 | 8.3 Years STANDARD_DEVIATION 1.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 11 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 120 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 46 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 39 Participants | 79 Participants | 40 Participants |
| Sex: Female, Male Female | 32 Participants | 67 Participants | 35 Participants |
| Sex: Female, Male Male | 31 Participants | 64 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 68 | 0 / 63 |
| other Total, other adverse events | 13 / 68 | 16 / 63 |
| serious Total, serious adverse events | 0 / 68 | 0 / 63 |
Outcome results
Primary
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.
Time frame: Over for 24 hours post-first dose on Day 1
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dextromethorphan Hydrobromide | Mean of Total Cough Counts: Over 24 Hours Post-First Dose on Day 1 | 457.1 cough counts | Standard Deviation 367.21 |
| Placebo | Mean of Total Cough Counts: Over 24 Hours Post-First Dose on Day 1 | 676.8 cough counts | Standard Deviation 814.33 |
Comparison: 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.p-value: 0.044995% CI: [0.6273, 0.9947]Negative Binomial Regression
Comparison: 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.p-value: 0.6293Negative Binomial Regression
Secondary
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.
Time frame: Between Dose 1 to Dose 2 on Day 1
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dextromethorphan Hydrobromide | Mean of Total Cough Counts: Between Dose 1 to Dose 2 on Day 1 | 32.73 cough counts | Standard Deviation 30.597 |
| Placebo | Mean of Total Cough Counts: Between Dose 1 to Dose 2 on Day 1 | 47.03 cough counts | Standard Deviation 57.729 |
Comparison: 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.p-value: 0.055295% CI: [0.6446, 1.0049]Negative Binomial Regression
Secondary
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.
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dextromethorphan Hydrobromide | Mean of Total Cough Counts: Between Dose 1 to Dose 2 on Day 1, and Between Dose 3 to Dose 4 on Day 2 | 26.13 cough counts | Standard Deviation 21.498 |
| Placebo | Mean of Total Cough Counts: Between Dose 1 to Dose 2 on Day 1, and Between Dose 3 to Dose 4 on Day 2 | 40.39 cough counts | Standard Deviation 49.896 |
Comparison: 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.p-value: 0.009895% CI: [0.5964, 0.9316]Negative Binomial Regression
Secondary
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.
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dextromethorphan Hydrobromide | Mean of Total Cough Counts: Between Dose 2 on Day 1 to Dose 3 on Day 2 | 9.70 cough counts | Standard Deviation 8.877 |
| Placebo | Mean of Total Cough Counts: Between Dose 2 on Day 1 to Dose 3 on Day 2 | 11.44 cough counts | Standard Deviation 13.193 |
Comparison: 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.p-value: 0.768495% CI: [0.7032, 1.2971]Negative Binomial Regression
Secondary
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.
Time frame: Between Dose 3 to Dose 4 on Day 2 (between first and second dose of Day 2)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dextromethorphan Hydrobromide | Mean of Total Cough Counts: Between Dose 3 to Dose 4 on Day 2 | 19.32 cough counts | Standard Deviation 16.752 |
| Placebo | Mean of Total Cough Counts: Between Dose 3 to Dose 4 on Day 2 | 33.62 cough counts | Standard Deviation 47.709 |
Comparison: 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.p-value: 0.02295% CI: [0.5178, 0.95]Negative Binomial Regression
Secondary
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.
Time frame: Over for 24 hours post-first dose on Day 1
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dextromethorphan Hydrobromide | Mean of Total Cough Time Accumulated Over a 24-Hour Period Post-First Dose on Day 1 | 350.5 seconds | Standard Deviation 268.95 |
| Placebo | Mean of Total Cough Time Accumulated Over a 24-Hour Period Post-First Dose on Day 1 | 502.7 seconds | Standard Deviation 566.57 |
Comparison: Analysis of covariance (ANCOVA) model contained treatment, study site (pooled), log-transformed baseline cough time and age group terms as factors.p-value: 0.097795% CI: [-0.4831, 0.0411]ANCOVA
Other Pre-specified
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.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dextromethorphan Hydrobromide | Change From Baseline in Afternoon Cough Frequency Assessed at Afternoon on Day 2, 3, and 4 | Baseline | 3.2 units on a scale | Standard Deviation 0.8 |
| Dextromethorphan Hydrobromide | Change From Baseline in Afternoon Cough Frequency Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 2 | -0.7 units on a scale | Standard Deviation 1.25 |
| Dextromethorphan Hydrobromide | Change From Baseline in Afternoon Cough Frequency Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 3 | -1.5 units on a scale | Standard Deviation 1.3 |
| Dextromethorphan Hydrobromide | Change From Baseline in Afternoon Cough Frequency Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 4 | -1.9 units on a scale | Standard Deviation 1.22 |
| Placebo | Change From Baseline in Afternoon Cough Frequency Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 4 | -1.8 units on a scale | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Afternoon Cough Frequency Assessed at Afternoon on Day 2, 3, and 4 | Baseline | 3.4 units on a scale | Standard Deviation 0.73 |
| Placebo | Change From Baseline in Afternoon Cough Frequency Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 3 | -1.4 units on a scale | Standard Deviation 1.27 |
| Placebo | Change From Baseline in Afternoon Cough Frequency Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 2 | -0.6 units on a scale | Standard Deviation 1.06 |
Comparison: 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.p-value: 0.024295% CI: [-0.5255, -0.0369]ANOVA
Comparison: 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.p-value: 0.2892ANOVA
Other Pre-specified
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.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dextromethorphan Hydrobromide | Change From Baseline in Afternoon Cough Severity Assessed at Afternoon on Day 2, 3, and 4 | Baseline | 2.8 units on a scale | Standard Deviation 0.83 |
| Dextromethorphan Hydrobromide | Change From Baseline in Afternoon Cough Severity Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 2 | -0.7 units on a scale | Standard Deviation 1.16 |
| Dextromethorphan Hydrobromide | Change From Baseline in Afternoon Cough Severity Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 3 | -1.4 units on a scale | Standard Deviation 1.15 |
| Dextromethorphan Hydrobromide | Change From Baseline in Afternoon Cough Severity Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 4 | -1.7 units on a scale | Standard Deviation 1.08 |
| Placebo | Change From Baseline in Afternoon Cough Severity Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 4 | -1.6 units on a scale | Standard Deviation 1.45 |
| Placebo | Change From Baseline in Afternoon Cough Severity Assessed at Afternoon on Day 2, 3, and 4 | Baseline | 3.1 units on a scale | Standard Deviation 0.84 |
| Placebo | Change From Baseline in Afternoon Cough Severity Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 3 | -1.4 units on a scale | Standard Deviation 1.24 |
| Placebo | Change From Baseline in Afternoon Cough Severity Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 2 | -0.6 units on a scale | Standard Deviation 0.98 |
Comparison: 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.p-value: 0.3268ANOVA
Comparison: 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.p-value: 0.006395% CI: [-0.517, -0.0858]ANOVA
Other Pre-specified
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.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dextromethorphan Hydrobromide | Change From Baseline in Child Global Question Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 4 | -2.1 units on a scale | Standard Deviation 0.87 |
| Dextromethorphan Hydrobromide | Change From Baseline in Child Global Question Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 2 | -1.1 units on a scale | Standard Deviation 1.02 |
| Dextromethorphan Hydrobromide | Change From Baseline in Child Global Question Assessed at Afternoon on Day 2, 3, and 4 | Baseline | 3.2 units on a scale | Standard Deviation 0.42 |
| Dextromethorphan Hydrobromide | Change From Baseline in Child Global Question Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 3 | -1.6 units on a scale | Standard Deviation 0.93 |
| Placebo | Change From Baseline in Child Global Question Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 4 | -1.7 units on a scale | Standard Deviation 1.26 |
| Placebo | Change From Baseline in Child Global Question Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 3 | -1.6 units on a scale | Standard Deviation 1.13 |
| Placebo | Change From Baseline in Child Global Question Assessed at Afternoon on Day 2, 3, and 4 | Baseline | 3.3 units on a scale | Standard Deviation 0.46 |
| Placebo | Change From Baseline in Child Global Question Assessed at Afternoon on Day 2, 3, and 4 | Change at Day 2 | -0.9 units on a scale | Standard Deviation 1.01 |
Comparison: ANOVA model with treatment, study site (pooled), baseline assessment by participant, interaction of treatment by age group and age group included in the model.p-value: 0.4093ANOVA
Comparison: 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.p-value: 0.024795% CI: [-0.4745, -0.0325]ANOVA
Other Pre-specified
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.
Time frame: Baseline (morning screening visit on Day 1); Within 30 minutes of waking, before morning dose on Days 2, 3, and 4
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dextromethorphan Hydrobromide | Change From Baseline in Impact of Cough on Sleep Assessed in Morning at Day 2, 3, and 4 | Baseline | 2.8 units on a scale | Standard Deviation 1.15 |
| Dextromethorphan Hydrobromide | Change From Baseline in Impact of Cough on Sleep Assessed in Morning at Day 2, 3, and 4 | Change at Day 2 | -0.8 units on a scale | Standard Deviation 1.56 |
| Dextromethorphan Hydrobromide | Change From Baseline in Impact of Cough on Sleep Assessed in Morning at Day 2, 3, and 4 | Change at Day 3 | -1.3 units on a scale | Standard Deviation 1.59 |
| Dextromethorphan Hydrobromide | Change From Baseline in Impact of Cough on Sleep Assessed in Morning at Day 2, 3, and 4 | Change at Day 4 | -1.8 units on a scale | Standard Deviation 1.57 |
| Placebo | Change From Baseline in Impact of Cough on Sleep Assessed in Morning at Day 2, 3, and 4 | Change at Day 4 | -1.9 units on a scale | Standard Deviation 1.74 |
| Placebo | Change From Baseline in Impact of Cough on Sleep Assessed in Morning at Day 2, 3, and 4 | Baseline | 3.0 units on a scale | Standard Deviation 1.19 |
| Placebo | Change From Baseline in Impact of Cough on Sleep Assessed in Morning at Day 2, 3, and 4 | Change at Day 3 | -1.4 units on a scale | Standard Deviation 1.67 |
| Placebo | Change From Baseline in Impact of Cough on Sleep Assessed in Morning at Day 2, 3, and 4 | Change at Day 2 | -0.7 units on a scale | Standard Deviation 1.45 |
Comparison: 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.p-value: 0.267995% CI: [-0.4112, 0.1146]ANOVA
Comparison: ANOVA model contained treatment, study site (pooled), screening assessment by participant, interaction of treatment by age group and age group included in the model.p-value: 0.2882ANOVA
Other Pre-specified
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.
Time frame: Baseline (morning screening visit on Day 1); Within 30 minutes of waking, before morning dose on Days 2, 3, and 4
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dextromethorphan Hydrobromide | Change From Baseline in Morning Cough Frequency Assessed in Morning at Day 2, 3, and 4 | Baseline | 3.4 units on a scale | Standard Deviation 0.65 |
| Dextromethorphan Hydrobromide | Change From Baseline in Morning Cough Frequency Assessed in Morning at Day 2, 3, and 4 | Change at Day 2 | -1.2 units on a scale | Standard Deviation 1.3 |
| Dextromethorphan Hydrobromide | Change From Baseline in Morning Cough Frequency Assessed in Morning at Day 2, 3, and 4 | Change at Day 4 | -2.0 units on a scale | Standard Deviation 1.2 |
| Dextromethorphan Hydrobromide | Change From Baseline in Morning Cough Frequency Assessed in Morning at Day 2, 3, and 4 | Change at Day 3 | -1.5 units on a scale | Standard Deviation 1.15 |
| Placebo | Change From Baseline in Morning Cough Frequency Assessed in Morning at Day 2, 3, and 4 | Change at Day 4 | -1.8 units on a scale | Standard Deviation 1.4 |
| Placebo | Change From Baseline in Morning Cough Frequency Assessed in Morning at Day 2, 3, and 4 | Baseline | 3.3 units on a scale | Standard Deviation 0.63 |
| Placebo | Change From Baseline in Morning Cough Frequency Assessed in Morning at Day 2, 3, and 4 | Change at Day 2 | -0.7 units on a scale | Standard Deviation 1.15 |
| Placebo | Change From Baseline in Morning Cough Frequency Assessed in Morning at Day 2, 3, and 4 | Change at Day 3 | -1.1 units on a scale | Standard Deviation 1.38 |
Comparison: 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.p-value: 0.019195% CI: [-0.5287, -0.0475]ANOVA
Comparison: ANOVA model contained treatment, study site (pooled), screening assessment by participant, interaction of treatment by age group and age group included in the model.p-value: 0.8355ANOVA
Other Pre-specified
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.
Time frame: Baseline (morning screening visit on Day 1); Within 30 minutes of waking, before morning dose on Days 2, 3, and 4
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dextromethorphan Hydrobromide | Change From Baseline in Morning Cough Severity Assessed in Morning at Day 2, 3, and 4 | Baseline | 3.1 units on a scale | Standard Deviation 0.54 |
| Dextromethorphan Hydrobromide | Change From Baseline in Morning Cough Severity Assessed in Morning at Day 2, 3, and 4 | Change at Day 2 | -1.1 units on a scale | Standard Deviation 0.89 |
| Dextromethorphan Hydrobromide | Change From Baseline in Morning Cough Severity Assessed in Morning at Day 2, 3, and 4 | Change at Day 3 | -1.4 units on a scale | Standard Deviation 0.96 |
| Dextromethorphan Hydrobromide | Change From Baseline in Morning Cough Severity Assessed in Morning at Day 2, 3, and 4 | Change at Day 4 | -1.9 units on a scale | Standard Deviation 1.1 |
| Placebo | Change From Baseline in Morning Cough Severity Assessed in Morning at Day 2, 3, and 4 | Change at Day 4 | -1.8 units on a scale | Standard Deviation 1.15 |
| Placebo | Change From Baseline in Morning Cough Severity Assessed in Morning at Day 2, 3, and 4 | Baseline | 3.1 units on a scale | Standard Deviation 0.6 |
| Placebo | Change From Baseline in Morning Cough Severity Assessed in Morning at Day 2, 3, and 4 | Change at Day 3 | -1.3 units on a scale | Standard Deviation 1.22 |
| Placebo | Change From Baseline in Morning Cough Severity Assessed in Morning at Day 2, 3, and 4 | Change at Day 2 | -0.6 units on a scale | Standard Deviation 1.19 |
Comparison: 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.p-value: 0.004995% CI: [-0.5299, -0.0956]ANOVA
Comparison: ANOVA model contained treatment, study site (pooled), screening assessment by participant, interaction of treatment by age group and age group included in the model.p-value: 0.8413ANOVA
Other Pre-specified
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.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dextromethorphan Hydrobromide | Pediatric Global Assessment of Satisfaction With Study Medication: By Participant, and Caregiver | By Participant: | 1.7 units on a scale | Standard Deviation 1.2 |
| Dextromethorphan Hydrobromide | Pediatric Global Assessment of Satisfaction With Study Medication: By Participant, and Caregiver | By Caregiver: | 1.8 units on a scale | Standard Deviation 1.07 |
| Placebo | Pediatric Global Assessment of Satisfaction With Study Medication: By Participant, and Caregiver | By Participant: | 1.6 units on a scale | Standard Deviation 1.26 |
| Placebo | Pediatric Global Assessment of Satisfaction With Study Medication: By Participant, and Caregiver | By Caregiver: | 1.9 units on a scale | Standard Deviation 1.16 |
Comparison: Caregiver: ANOVA model with treatment, study site (pooled), and age group included in the model.p-value: 0.491495% CI: [-0.5292, 0.2556]ANOVA
Comparison: Participant: ANOVA model with treatment, study site (pooled), and age group included in the model.p-value: 0.565295% CI: [-0.3081, 0.5614]ANOVA
Comparison: Participant: ANOVA model with treatment, study site (pooled), interaction of treatment by age group and age group included in the model.p-value: 0.1029ANOVA
Comparison: Caregiver: ANOVA model with treatment, study site (pooled), interaction of treatment by age group and age group included in the model.p-value: 0.4736ANOVA