Common Cold, Infections, Upper Respiratory Tract
Conditions
Keywords
randomized, parallel, double-blind, placebo-controlled, cough, efficacy, safety, dextromethorphan
Brief summary
15 mg dextromethorphan hydrobromide will be better than placebo with respect to reducing the number of coughs over 6 hours and reducing the subjective severity of cough over 6 hours.
Detailed description
In light of protocol changes required due to methodological and operational issues, including background noise in cough recordings which could impact data interpretation, the study has been terminated.
Interventions
DRUGDextromethorphan
A single 10 mL dose of Children's Triaminic Syrup (Dextromethorphan Hydrobromide 7.5 mg per 5 mL (total dose of 15 mg)
DRUGPlacebo
A single 10 mL dose of matching placebo syrup
Sponsors
AccuDial Pharmaceutical, Inc.
Boehringer Ingelheim
McNeil Consumer Healthcare Division of McNEIL-PPC, Inc.
Novartis
Perrigo Company
Procter and Gamble
Reckitt Benckiser LLC
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
Male or female healthy children ages 6 to under 12 years who are symptomatic with a cough due to a cold or acute URTI characterized by: * Onset of cold/URTI symptoms occurring no more than 10 days prior to Visit 1; * At least 5 coughs during the second 30-minute period of the 60-minute baseline period. General good health, aside from a common cold, and has no contraindications to the study or rescue medication
Exclusion criteria
* Acute, subchronic, or chronic cough due to any other condition other than a common cold History of clinically significant cardiovascular, pulmonary, hepatic, renal, neurological, hematological, autoimmune, psychiatric, metabolic, gastro-intestinal or endocrine disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Cough Count | Up to 6 hours post-dose | Total cough count was done by trained assessors using continuous digital video and audio recordings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Baseline, 1, 2, 3, 4, 5, 6 hours | Verbal cough severity score was assessed on a 5-point categorical rating scale in accordance to the question How much have you coughed in the last hour?, where 0 = not at all, 1 = a tiny bit, 2 = a little, 3 = some and 4 = a lot. The change from baseline values were derived by subtracting each post baseline value from the baseline value, and ranged from -4 to 4; higher score indicated a better improvement. |
| Change From Baseline in Perceived Numerical Cough Severity Scale for 6 Hour Post-Dose Period | Baseline, 1, 2, 3, 4, 5, 6 hour post-dose | Perceived numerical cough severity score was assessed on an 11-point categorical rating scale in accordance to the question How much have you coughed in the last hour?, where 0 = did not cough at all and 10 = cough a lot. The change from baseline for the 6-hour post-dosing period was calculated as the average of change from baseline (i.e. baseline value minus the post baseline value) measurements of Hour 1 to Hour 6, thus the change from baseline values ranged from -10 to 10; higher score indicated a better improvement. |
| Change From Baseline in Perceived Verbal Cough Severity Scale for 6 Hour Post-Dose Period | Baseline, 1, 2, 3, 4, 5, 6 hours post-dose | Perceived verbal cough severity score was assessed on a 5-point categorical rating scale in accordance to the question How much have you coughed in the last hour?, where 0 = not at all, 1 = a tiny bit, 2 = a little, 3 = some and 4 = a lot. The change from baseline over the 6-hour post-dosing period calculated as the average of change from baseline \[that is (i.e.) baseline value minus the post baseline value\] measurements of Hour 1 to Hour 6, thus the change from baseline ranged from -4 to 4; higher score indicated a better improvement. |
| Participants' Global Assessment of Cough: Cough Severity | Within 5 minutes after Hour 6 | Participant global assessment of cough with the assistance of parent or legal guardian was scored on a 5-point categorical scale based on response to the question How much have you coughed in the past 6 hours? where 0 = not at all, 1 = a tiny bit, 2 = a little, 3 = some and 4 = a lot. |
| Participants' Global Assessment of Cough: Relief From Cough | Within 5 minutes after Hour 6 | Participant global assessment of cough with the assistance of parent or legal guardian was scored on a 5-point categorical scale based on response to the question From when you woke up this morning until now, how much better is your cough? where 0 = not at all better, 1 = a tiny bit better, 2 = a little better, 3 = better and 4 = a lot better. |
| Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Baseline, 1, 2, 3, 4, 5, 6 hours | Numerical cough severity score was assessed on an 11-point categorical rating scale in accordance to the question How much have you coughed in the last hour?, wherein 0 = did not cough at all and 10 = cough a lot. The change from baseline was derived by subtracting the post baseline value from the baseline value and ranged from -10 to 10; higher score indicated a better improvement. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Single oral dose of placebo solution matched to 15 milligram (mg) \[10 milliliter (mL/)\] dextromethorphan hydrobromide. | 55 |
| Dextromethorphan Hydrobromide Single oral dose of 15 mg (10 mL) dextromethorphan hydrobromide syrup \[7.5 mg/5 milliliter (mL)\]. | 52 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 3 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Dextromethorphan Hydrobromide | Total |
|---|---|---|---|
| Age Continuous | 8.9 Years STANDARD_DEVIATION 1.8 | 8.9 Years STANDARD_DEVIATION 1.6 | 8.9 Years STANDARD_DEVIATION 1.7 |
| Sex: Female, Male Female | 32 Participants | 25 Participants | 57 Participants |
| Sex: Female, Male Male | 23 Participants | 27 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 55 | 6 / 52 |
| serious Total, serious adverse events | 0 / 55 | 0 / 52 |
Outcome results
Primary
Total Cough Count
Total cough count was done by trained assessors using continuous digital video and audio recordings.
Time frame: Up to 6 hours post-dose
Population: Intent-to-treat (ITT) population included all randomized participants who received study medication, provided baseline efficacy data and any post baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Cough Count | 238.7 Cough counts | Standard Deviation 252.3 |
| Dextromethorphan Hydrobromide | Total Cough Count | 190.9 Cough counts | Standard Deviation 190.6 |
Comparison: Odds Ratio and corresponding 95 percent (%) confidence interval (CI) were assessed from the negative binomial regression model.p-value: 0.25295% CI: [0.59, 1.15]Negative binomial regression
Secondary
Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6
Numerical cough severity score was assessed on an 11-point categorical rating scale in accordance to the question How much have you coughed in the last hour?, wherein 0 = did not cough at all and 10 = cough a lot. The change from baseline was derived by subtracting the post baseline value from the baseline value and ranged from -10 to 10; higher score indicated a better improvement.
Time frame: Baseline, 1, 2, 3, 4, 5, 6 hours
Population: ITT population included all randomized participants who received study medication, provided baseline efficacy data and any post baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 1 hour | 2.0 Units on a scale | Standard Deviation 2.9 |
| Placebo | Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 4 hours | 2.9 Units on a scale | Standard Deviation 2.8 |
| Placebo | Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 3 hours | 2.7 Units on a scale | Standard Deviation 2.7 |
| Placebo | Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 5 hours | 3.6 Units on a scale | Standard Deviation 2.8 |
| Placebo | Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 6 hours | 3.4 Units on a scale | Standard Deviation 3.3 |
| Placebo | Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 2 hours | 2.5 Units on a scale | Standard Deviation 2.6 |
| Dextromethorphan Hydrobromide | Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 6 hours | 2.8 Units on a scale | Standard Deviation 3.8 |
| Dextromethorphan Hydrobromide | Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 2 hours | 2.1 Units on a scale | Standard Deviation 3.5 |
| Dextromethorphan Hydrobromide | Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 5 hours | 3.0 Units on a scale | Standard Deviation 3.2 |
| Dextromethorphan Hydrobromide | Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 1 hour | 2.0 Units on a scale | Standard Deviation 2.8 |
| Dextromethorphan Hydrobromide | Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 3 hours | 2.3 Units on a scale | Standard Deviation 3.5 |
| Dextromethorphan Hydrobromide | Change From Baseline in Numerical Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 4 hours | 2.5 Units on a scale | Standard Deviation 3.6 |
Comparison: 1 hour: treatment difference and corresponding 95% CI were calculated based on LS means from ANOVA model.p-value: 0.95495% CI: [-1.03, 0.97]ANOVA
Comparison: 2 hours: treatment difference and corresponding 95% CI were calculated based on LS means from ANOVA model.p-value: 0.42695% CI: [-1.54, 0.65]ANOVA
Comparison: 3 hours: treatment difference and corresponding 95% CI were calculated based on LS means from ANOVA model.p-value: 0.39695% CI: [-1.49, 0.6]ANOVA
Comparison: 4 hours: treatment difference and corresponding 95% CI were calculated based on LS means from ANOVA model.p-value: 0.40295% CI: [-1.63, 0.66]ANOVA
Comparison: 5 hours: treatment difference and corresponding 95% CI were calculated based on LS means from ANOVA model.p-value: 0.20495% CI: [-1.75, 0.38]ANOVA
Comparison: 6 hours: treatment difference and corresponding 95% CI were calculated based on LS means from ANOVA model.p-value: 0.17995% CI: [-2.06, 0.39]ANOVA
Secondary
Change From Baseline in Perceived Numerical Cough Severity Scale for 6 Hour Post-Dose Period
Perceived numerical cough severity score was assessed on an 11-point categorical rating scale in accordance to the question How much have you coughed in the last hour?, where 0 = did not cough at all and 10 = cough a lot. The change from baseline for the 6-hour post-dosing period was calculated as the average of change from baseline (i.e. baseline value minus the post baseline value) measurements of Hour 1 to Hour 6, thus the change from baseline values ranged from -10 to 10; higher score indicated a better improvement.
Time frame: Baseline, 1, 2, 3, 4, 5, 6 hour post-dose
Population: ITT population included all randomized participants who received study medication, provided baseline efficacy data and any post baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Perceived Numerical Cough Severity Scale for 6 Hour Post-Dose Period | Baseline | 6.8 Units on a scale | Standard Deviation 2.2 |
| Placebo | Change From Baseline in Perceived Numerical Cough Severity Scale for 6 Hour Post-Dose Period | Change for 6 hour post-dose period | 2.8 Units on a scale | Standard Deviation 2.5 |
| Dextromethorphan Hydrobromide | Change From Baseline in Perceived Numerical Cough Severity Scale for 6 Hour Post-Dose Period | Baseline | 7.0 Units on a scale | Standard Deviation 2.3 |
| Dextromethorphan Hydrobromide | Change From Baseline in Perceived Numerical Cough Severity Scale for 6 Hour Post-Dose Period | Change for 6 hour post-dose period | 2.5 Units on a scale | Standard Deviation 3.1 |
Comparison: Treatment difference and corresponding 95% CI were calculated based on LS means from ANOVA model.p-value: 0.30495% CI: [-1.43, 0.45]ANOVA
Secondary
Change From Baseline in Perceived Verbal Cough Severity Scale for 6 Hour Post-Dose Period
Perceived verbal cough severity score was assessed on a 5-point categorical rating scale in accordance to the question How much have you coughed in the last hour?, where 0 = not at all, 1 = a tiny bit, 2 = a little, 3 = some and 4 = a lot. The change from baseline over the 6-hour post-dosing period calculated as the average of change from baseline \[that is (i.e.) baseline value minus the post baseline value\] measurements of Hour 1 to Hour 6, thus the change from baseline ranged from -4 to 4; higher score indicated a better improvement.
Time frame: Baseline, 1, 2, 3, 4, 5, 6 hours post-dose
Population: ITT population included all randomized participants who received study medication, provided baseline efficacy data and any post baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Perceived Verbal Cough Severity Scale for 6 Hour Post-Dose Period | Baseline | 3.0 Units on a scale | Standard Deviation 0.9 |
| Placebo | Change From Baseline in Perceived Verbal Cough Severity Scale for 6 Hour Post-Dose Period | Change for 6 hour post-dose period | 1.3 Units on a scale | Standard Deviation 1.1 |
| Dextromethorphan Hydrobromide | Change From Baseline in Perceived Verbal Cough Severity Scale for 6 Hour Post-Dose Period | Baseline | 2.9 Units on a scale | Standard Deviation 0.9 |
| Dextromethorphan Hydrobromide | Change From Baseline in Perceived Verbal Cough Severity Scale for 6 Hour Post-Dose Period | Change for 6 hour post-dose period | 1.1 Units on a scale | Standard Deviation 1.1 |
Comparison: Treatment difference and corresponding 95% CI were calculated based on least-square (LS) means from analysis of variance (ANOVA) model.p-value: 0.13495% CI: [-0.6, 0.08]ANOVA
Secondary
Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6
Verbal cough severity score was assessed on a 5-point categorical rating scale in accordance to the question How much have you coughed in the last hour?, where 0 = not at all, 1 = a tiny bit, 2 = a little, 3 = some and 4 = a lot. The change from baseline values were derived by subtracting each post baseline value from the baseline value, and ranged from -4 to 4; higher score indicated a better improvement.
Time frame: Baseline, 1, 2, 3, 4, 5, 6 hours
Population: ITT population included all randomized participants who received study medication, provided baseline efficacy data and any post baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 1 hour | 1.0 Units on a scale | Standard Deviation 1.2 |
| Placebo | Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 3 hours | 1.3 Units on a scale | Standard Deviation 1.2 |
| Placebo | Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 2 hours | 1.2 Units on a scale | Standard Deviation 1.2 |
| Placebo | Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 4 hours | 1.4 Units on a scale | Standard Deviation 1.3 |
| Placebo | Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 5 hours | 1.7 Units on a scale | Standard Deviation 1.3 |
| Placebo | Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 6 hours | 1.5 Units on a scale | Standard Deviation 1.4 |
| Dextromethorphan Hydrobromide | Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 5 hours | 1.2 Units on a scale | Standard Deviation 1.4 |
| Dextromethorphan Hydrobromide | Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 2 hours | 0.9 Units on a scale | Standard Deviation 1.4 |
| Dextromethorphan Hydrobromide | Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 4 hours | 1.1 Units on a scale | Standard Deviation 1.4 |
| Dextromethorphan Hydrobromide | Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 3 hours | 0.9 Units on a scale | Standard Deviation 1.4 |
| Dextromethorphan Hydrobromide | Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 1 hour | 0.9 Units on a scale | Standard Deviation 1.2 |
| Dextromethorphan Hydrobromide | Change From Baseline in Verbal Cough Severity Scale at Hours 1, 2, 3, 4, 5 and 6 | Change at 6 hours | 1.2 Units on a scale | Standard Deviation 1.4 |
Comparison: 1 hour: treatment difference and corresponding 95% CI were calculated based on LS means from ANOVA model.p-value: 0.76895% CI: [-0.45, 0.33]ANOVA
Comparison: 2 hours: treatment difference and corresponding 95% CI were calculated based on LS means from ANOVA model.p-value: 0.35895% CI: [-0.64, 0.23]ANOVA
Comparison: 3 hours: treatment difference and corresponding 95% CI were calculated based on LS means from ANOVA model.p-value: 0.13995% CI: [-0.74, 0.1]ANOVA
Comparison: 4 hours: treatment difference and corresponding 95% CI were calculated based on LS means from ANOVA model.p-value: 0.36495% CI: [-0.68, 0.25]ANOVA
Comparison: 5 hours: treatment difference and corresponding 95% CI were calculated based on LS means from ANOVA model.p-value: 0.03995% CI: [-0.9, -0.02]ANOVA
Comparison: 6 hours: treatment difference and corresponding 95% CI were calculated based on LS means from ANOVA model.p-value: 0.20695% CI: [-0.75, 0.16]ANOVA
Secondary
Participants' Global Assessment of Cough: Cough Severity
Participant global assessment of cough with the assistance of parent or legal guardian was scored on a 5-point categorical scale based on response to the question How much have you coughed in the past 6 hours? where 0 = not at all, 1 = a tiny bit, 2 = a little, 3 = some and 4 = a lot.
Time frame: Within 5 minutes after Hour 6
Population: ITT population included all randomized participants who received study medication, provided baseline efficacy data and any post baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Participants' Global Assessment of Cough: Cough Severity | 3.1 Units on a scale | Standard Deviation 0.9 |
| Dextromethorphan Hydrobromide | Participants' Global Assessment of Cough: Cough Severity | 3.0 Units on a scale | Standard Deviation 1.3 |
Comparison: Treatment difference and the associated 95% CI were based on the weighted Gamma statistics.p-value: 0.52395% CI: [-0.21, 0.39]Cochran-Mantel-Haenszel
Secondary
Participants' Global Assessment of Cough: Relief From Cough
Participant global assessment of cough with the assistance of parent or legal guardian was scored on a 5-point categorical scale based on response to the question From when you woke up this morning until now, how much better is your cough? where 0 = not at all better, 1 = a tiny bit better, 2 = a little better, 3 = better and 4 = a lot better.
Time frame: Within 5 minutes after Hour 6
Population: ITT population included all randomized participants who received study medication, provided baseline efficacy data and any post baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Participants' Global Assessment of Cough: Relief From Cough | 2.9 Units on a scale | Standard Deviation 1 |
| Dextromethorphan Hydrobromide | Participants' Global Assessment of Cough: Relief From Cough | 2.7 Units on a scale | Standard Deviation 1.3 |
Comparison: Treatment difference and the associated 95% CI were based on the weighted Gamma statistics.p-value: 0.79695% CI: [-0.35, 0.24]Cochran-Mantel-Haenszel