Acute Upper Respiratory Tract Infection
Conditions
Brief summary
The study is designed to meet regulatory requirement outside the US. The dosing regimen and assessments timepoints were dictated by immediate release (IR) guaifenesin (GGE) and do not match approved Mucinex labeling in the U.S. The purpose of this study is to determine whether Mucinex is effective and non-inferior as compared to placebo and immediate release guaifenesin in the treatment of symptoms of acute upper respiratory infections. This design was required based on EU regulatory guidance.
Interventions
DRUGMucinex
Mucinex combines immediate-release (IR) and modified-release guaifenesin in a bilayer tablet. Each tablet was 600 mg of guaifenesin and taken by mouth with a full glass of water.
DRUGImmediate-release Guaifenesin
Each tablet was 200 mg of immediate-release (IR) guaifenesin and taken by mouth with a full glass of water.
DRUGPlacebo
Placebo tablets in two formulations to match either Mucinex or IR guaifenesin taken by mouth with a full glass of water
Sponsors
Reckitt Benckiser LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1\. Has developed cold symptoms within 3 days prior to dosing on Day 1.
Exclusion criteria
1. Chronic illnesses. 2. Febrile illness \> 101 F within 7 days prior to Day 1, 3. Pregnant. 4. Known current malignancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary Scores on the SUM8 Daily Cough and Phlegm Diary Card On the Morning of Day 4 | Day 4 | Participants completed diary cards twice a day that asked questions about their cough and phlegm status. The Daily Cough and Phlegm Diary Card consisted of eleven questions, eight core questions plus three questions that were answered dependent upon the response to core questions. The SUM8 consisted of the sum of the answers to the eight core questions. Each question was answered on a scale of 0-4, with 4 representing the greatest severity of symptoms. The SUM8 thus had a scale range of 0-32 with 0 representing best possible symptoms, and 32 representing greatest severity of symptoms. |
| Summary Scores on the SUM8 Daily Cough and Phlegm Diary Card On the Morning of Day 5 | Day 5 | Participants completed diary cards twice a day that asked questions about their cough and phlegm status. The Daily Cough and Phlegm Diary Card consisted of eleven questions, eight core questions plus three questions that were answered dependent upon the response to core questions. The SUM8 consisted of the sum of the answers to the eight core questions. Each question was answered on a scale of 0-4, with 4 representing the greatest severity of symptoms. The SUM8 thus had a scale range of 0-32 with 0 representing best possible symptoms, and 32 representing greatest severity of symptoms. |
Countries
United States
Participant flow
Pre-assignment details
A total of 3215 patients were screened for enrollment, and 405 did not proceed in the study. Participants were randomized in a 2:2:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| Mucinex 2400 mg/Day The study is designed to meet regulatory requirement outside the US. The dosing regimen and assessments timepoints were dictated by IR GGE and do not match approved Mucinex labeling. Participants were instructed to take 2 Mucinex 600-mg tablets and 1 placebo tablet matching the 200 mg IR guaifenesin tablet by mouth, every 12 hours for 7 days. To ensure complete blinding, on Hours 6 and 18, this treatment group took 2 matching Mucinex placebo tablets combined with 1 IR guaifenesin placebo tablet. | 1,122 |
| Immediate-release Guaifenesin 800 mg/Day The dosing regimen and assessments timepoints were dictated by immediate-release guaifenesin (IR GGE). Participants were instructed to take 1 immediate-release guaifenesin (IR GGE) 200 mg tablet and 2 matching Mucinex placebo tablets by mouth, every 6 hours for 7 days. | 1,122 |
| Placebo Double dummy technique was employed requiring a large number of tablets and water to be consumed. Participants were instructed to take 2 matching Mucinex placebo tablets combined with 1 matching IR guaifenesin placebo tablet by mouth, every 6 hours for 7 days. | 561 |
| Total | 2,805 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 | 2 |
| Overall Study | Assigned but never dosed | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 2 | 1 | 0 |
| Overall Study | Lost to Follow-up | 17 | 15 | 9 |
| Overall Study | Physician Decision | 5 | 6 | 0 |
| Overall Study | Protocol Violation | 3 | 2 | 2 |
| Overall Study | Sponsor decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 11 | 3 |
Baseline characteristics
| Characteristic | Mucinex 2400 mg/Day | Immediate-release Guaifenesin 800 mg/Day | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 37.3 years STANDARD_DEVIATION 13.81 | 36.8 years STANDARD_DEVIATION 13.81 | 37.9 years STANDARD_DEVIATION 14.09 | 37.2 years STANDARD_DEVIATION 13.87 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 participants | 7 participants | 2 participants | 10 participants |
| Race/Ethnicity, Customized Asian | 31 participants | 25 participants | 13 participants | 69 participants |
| Race/Ethnicity, Customized Black or African American | 382 participants | 419 participants | 200 participants | 1001 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 4 participants | 3 participants | 3 participants | 10 participants |
| Race/Ethnicity, Customized Other | 18 participants | 12 participants | 16 participants | 46 participants |
| Race/Ethnicity, Customized White | 686 participants | 656 participants | 327 participants | 1669 participants |
| Sex: Female, Male Female | 670 Participants | 668 Participants | 333 Participants | 1671 Participants |
| Sex: Female, Male Male | 452 Participants | 454 Participants | 228 Participants | 1134 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 84 / 1,122 | 85 / 1,122 | 41 / 561 |
| serious Total, serious adverse events | 0 / 1,122 | 0 / 1,122 | 1 / 561 |
Outcome results
Primary
Summary Scores on the SUM8 Daily Cough and Phlegm Diary Card On the Morning of Day 4
Participants completed diary cards twice a day that asked questions about their cough and phlegm status. The Daily Cough and Phlegm Diary Card consisted of eleven questions, eight core questions plus three questions that were answered dependent upon the response to core questions. The SUM8 consisted of the sum of the answers to the eight core questions. Each question was answered on a scale of 0-4, with 4 representing the greatest severity of symptoms. The SUM8 thus had a scale range of 0-32 with 0 representing best possible symptoms, and 32 representing greatest severity of symptoms.
Time frame: Day 4
Population: Modified Intent-To-Treat (i.e., all randomized and treated subjects who had a baseline and at least 1 post-baseline set of assessments). Only participants who completed Daily Cough and Phlegm Diary Cards on the morning of Day 4 are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mucinex 2400 mg/Day | Summary Scores on the SUM8 Daily Cough and Phlegm Diary Card On the Morning of Day 4 | 12.96 units on a scale | Standard Deviation 6.226 |
| Immediate-release Guaifenesin 800 mg/Day | Summary Scores on the SUM8 Daily Cough and Phlegm Diary Card On the Morning of Day 4 | 12.87 units on a scale | Standard Deviation 6.078 |
| Placebo | Summary Scores on the SUM8 Daily Cough and Phlegm Diary Card On the Morning of Day 4 | 12.71 units on a scale | Standard Deviation 5.828 |
Primary
Summary Scores on the SUM8 Daily Cough and Phlegm Diary Card On the Morning of Day 5
Participants completed diary cards twice a day that asked questions about their cough and phlegm status. The Daily Cough and Phlegm Diary Card consisted of eleven questions, eight core questions plus three questions that were answered dependent upon the response to core questions. The SUM8 consisted of the sum of the answers to the eight core questions. Each question was answered on a scale of 0-4, with 4 representing the greatest severity of symptoms. The SUM8 thus had a scale range of 0-32 with 0 representing best possible symptoms, and 32 representing greatest severity of symptoms.
Time frame: Day 5
Population: Modified Intent-to-Treat(i.e., all randomized and treated subjects who had a baseline and at least 1 post-baseline set of assessments). Only participants who completed Daily Cough and Phlegm Diary Cards on the morning of Day 5 are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mucinex 2400 mg/Day | Summary Scores on the SUM8 Daily Cough and Phlegm Diary Card On the Morning of Day 5 | 10.92 units on a scale | Standard Deviation 6.448 |
| Immediate-release Guaifenesin 800 mg/Day | Summary Scores on the SUM8 Daily Cough and Phlegm Diary Card On the Morning of Day 5 | 10.80 units on a scale | Standard Deviation 6.261 |
| Placebo | Summary Scores on the SUM8 Daily Cough and Phlegm Diary Card On the Morning of Day 5 | 11.05 units on a scale | Standard Deviation 5.9 |