Background
Methods
Clinical pilot study
Study design and objectives
Subject selection
Treatment
Assessments
Statistical methods
Validation study
Study design and objectives
Subject selection (Phase I)
Validation content validity assessments (Phase I)
Statistical analysis
Validation psychometric evaluation (Phase II)
Results
Clinical pilot study
Patient population
Placebo | ER guaifenesin | Overall | |
---|---|---|---|
(n = 190) | (n = 188) | (N = 378) | |
Mean age, years ± SD
| 40.8 ± 15.04 | 41.1 ± 13.91 | 41.0 ± 14.47 |
Age range, years
| 13 – 83 | 18 – 85 | 13 – 85 |
Sex, male %
| 55.8 | 48.9 | 52.4 |
Sex, female %
| 44.2 | 51.1 | 47.6 |
Race, White %
| 61.1 | 60.6 | 60.8 |
Black % | 33.2 | 36.7 | 34.9 |
Asian % | 4.2 | 1.6 | 2.9 |
American Indian or Alaska Native % | 1.6 | 0.5 | 1.1 |
Other % | 0 | 0.5 | 0.3 |
Ethnicity, Hispanic or Latino %
| 5.3 | 7.4 | 6.3 |
Not Hispanic or Latino % | 94.7 | 92.6 | 93.7 |
Onset day of cold symptoms before study entry
| |||
−8 days %
| 0.5 | 0 | 0.3 |
−6 days %
| 0.5 | 0 | 0.3 |
−5 days %
| 3.7 | 5.3 | 4.5 |
−4 days %
| 26.8 | 19.7 | 23.3 |
−3 days %
| 39.5 | 38.3 | 38.9 |
−2 days %
| 21.1 | 32.4 | 26.7 |
−1 days %
| 7.4 | 4.3 | 5.8 |
0 days %
| 0.5 | 0 | 0.3 |
Onset day of productive cough before study entry
| |||
−7 days %
| 0.5 | 0 | 0.3 |
−5 days %
| 0 | 0.5 | 0.3 |
−4 days %
| 2.6 | 1.1 | 1.9 |
−3 days %
| 14.7 | 10.1 | 12.4 |
−2 days %
| 46.3 | 50.5 | 48.4 |
−1 days %
| 31.1 | 34.0 | 32.5 |
0 days %
| 4.7 | 3.7 | 4.2 |
Diagnosis before study entry
| |||
Acute nasopharyngitis/rhinopharyngitis %
| 81.6 | 83.0 | 82.3 |
Acute bronchitis %
| 10.0 | 6.9 | 8.5 |
Acute sinusitis %
| 4.7 | 6.9 | 5.8 |
Acute pharyngitis %
| 2.6 | 2.1 | 2.4 |
Acute laryngitis %
| 0.5 | 0.5 | 0.5 |
Other %
| 0.5 | 0.5 | 0.5 |
Efficacy evaluation
Study Day | |||||||
---|---|---|---|---|---|---|---|
Questions | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
1. Over the last 24 hours, how often did you bring up phlegm?
| |||||||
2. Over the last 24 hours, how often did your phlegm make it difficult for you to breathe?
| p < 0.10 | ||||||
3. Over the last 24 hours, how often did you feel uncomfortable about bothering other people while bringing up phlegm?
| |||||||
4. Over the last 24 hours, how annoyed were you by your phlegm?
| |||||||
5. Over the last 24 hours, how often did your phlegm interfere with your ability to speak?
| p < 0.05 | ||||||
6. Over the last 24 hours, how often did your phlegm prevent you from going to public places?
| |||||||
7. Over the last 24 hours, how often did you have to interrupt your usual activities to get rid of your phlegm?
| |||||||
8. Over the last 24 hours, how thick was your phlegm?
| p < 0.05 | ||||||
9. Over the last 24 hours, how difficult was it for you to bring up phlegm?
| p < 0.10 | ||||||
10. How much did you cough when you woke up in the morning?
| p < 0.10 | p < 0.05 | p < 0.05 | p < 0.10 | |||
11. How often did you cough during the day today?
| p < 0.05 | p < 0.05 | p < 0.10 |
Day 3 | Day 3 | Day 4 | Day 4 | Day 8 | |
---|---|---|---|---|---|
Hour 0 | Hour 3 | Hour 0 | Hour 3 | ||
Congestion
| |||||
Mucus
| p < 0.10 | p < 0.10 | p < 0.10 | ||
Cough
| p < 0.05 |
Endpoint | Placebo | ER guaifenesin | p-value |
---|---|---|---|
1. Excluding questions 3, 6, and 7 (SUM8)
| |||
Overall |
−5.7
|
−7.1
|
0.0372
|
1 day since onset of symptoms |
−6.2
|
−8.4
|
0.0339
|
2 days since onset of symptoms | −6.1 | −7.5 | 0.2281 |
3 days since onset of symptoms | −5.6 | −6.2 | 0.4424 |
4 days since onset of symptoms | −5.4 | −7.5 | 0.2475 |
5 days since onset of symptoms | −7.9 | −8.0 | 0.6814 |
Diagnosis: acute rhinopharyngitis | −5.9 | −6.8 | 0.1521 |
Diagnosis: acute sinusitis | −3.0 | −8.0 | 0.0534 |
Diagnosis: acute pharyngitis | −15.3 | −5.5 | NA |
Diagnosis: acute bronchitis |
−4.3
|
−9.8
|
0.0064
|
2. Including questions 5, 8, 10, and 11 only
| |||
Overall |
−3.0
|
−3.9
|
0.0059
|
1 day since onset of symptoms |
−2.9
|
−4.6
|
0.0093
|
2 days since onset of symptoms | −3.5 | −4.2 | 0.1499 |
3 days since onset of symptoms | −2.7 | −3.4 | 0.1439 |
4 days since onset of symptoms | −2.8 | −4.0 | 0.1342 |
5 days since onset of symptoms | −5.3 | −4.3 | 0.5617 |
Diagnosis: acute rhinopharyngitis |
−3.0
|
−3.8
|
0.0263
|
Diagnosis: acute sinusitis | −1.8 | −4.3 | 0.0715 |
Diagnosis: acute pharyngitis | −8.7 | −3.5 | NA |
Diagnosis: acute bronchitis |
−2.1
|
−4.7
|
0.0368
|
3. Including questions 8, 9, 10, and 11 only
| |||
Overall |
−2.5
|
−3.2
|
0.0062
|
1 day since onset of symptoms |
−1.8
|
−4.4
|
0.0286
|
2 days since onset of symptoms | −2.6 | −3.4 | 0.0965 |
3 days since onset of symptoms | −2.7 | −2.6 | 0.4421 |
4 days since onset of symptoms | −2.4 | −3.1 | 0.2021 |
5 days since onset of symptoms | −3.4 | −4.6 | 0.6586 |
Diagnosis: acute rhinopharyngitis |
−2.5
|
−3.2
|
0.0176
|
Diagnosis: acute sinusitis | −0.6 | −2.6 | 0.1035 |
Diagnosis: acute pharyngitis | −8.0 | −2.3 | NA |
Diagnosis: acute bronchitis |
−2.1
|
−4.0
|
0.0330
|
Safety
Placebo | ER guaifenesin | |||
---|---|---|---|---|
System organ class | (n = 189) | (n = 188) | ||
Preferred term | Possible | Probable | Possible | Probable |
Total number of treatment-emergent AEs
| 4 | 2 | 7 | 5 |
Number of unique patients with at least one AE
| 2.1 | 1.1 | 3.7 | 2.7 |
Gastrointestinal disorders %
| 1.6 | 0.5 | 0.5 | 1.6 |
Abdominal discomfort %
| 0.5 | 0 | 0 | 0 |
Diarrhoea %
| 0.5 | 0 | 0 | 0 |
Dry mouth %
| 0 | 0.5 | 0 | 0 |
Nausea %
| 0 | 0 | 0.5 | 1.6 |
Vomiting %
| 0.5 | 0 | 0 | 0 |
Nervous system disorders %
| 0 | 0.5 | 3.2 | 0.5 |
Headache %
| 0 | 0.5 | 2.1 | 0.5 |
Sinus headache %
| 0 | 0 | 0.5 | 0 |
Somnolence, %
| 0 | 0 | 0.5 | 0 |
Psychiatric disorders %
| 0 | 0 | 0 | 0.5 |
Insomnia %
| 0 | 0 | 0 | 0.5 |
Skin and subcutaneous tissue disorders %
| 0.5 | 0 | 0 | 0 |
Rash %
| 0.5 | 0 | 0 | 0 |
Validation study
Item | Cronbach’s alpha | Cronbach’s alpha with item deleted | ||||
---|---|---|---|---|---|---|
Day 1 | Day 4 | Day 8 | Day 1 | Day 4 | Day 8 | |
Subscale score alpha | 0.76 | 0.87 | 0.90 | |||
(n = 310) | (n = 305) | (n = 290) | ||||
1. Bring up phlegm | 0.73 | 0.84 | 0.88 | |||
2. Difficult to breathe | 0.72 | 0.84 | 0.88 | |||
4. Annoyed by phlegm | 0.71 | 0.83 | 0.87 | |||
5. Interference with ability to speak | 0.71 | 0.84 | 0.88 | |||
8. Phlegm thickness | 0.72 | 0.85 | 0.88 | |||
9. Difficulty bringing up phlegm | 0.81 | 0.90 | 0.93 | |||
10. Cough when woke up | 0.73 | 0.84 | 0.88 | |||
11. Cough during day | 0.74 | 0.84 | 0.88 |
Daily Cough and Phlegm Diary – 8 items | |||
---|---|---|---|
Symptom subscale – Day 1 | Symptom subscale – Day 4 | Symptom subscale – Day 8 | |
Spontaneous symptom assessment: congestion | 0.15* | 0.50‡ | 0.64‡ |
Spontaneous symptom assessment: mucus | 0.19† | 0.42‡ | 0.59‡ |
Spontaneous symptom assessment: cough | 0.20† | 0.52‡ | 0.57‡ |
Patient’s End-of-Treatment Assessment | 0.07 | −0.17* | −0.32‡ |
WURSS-21 Total | 0.50‡ | 0.68‡ | 0.70‡ |
WURSS-21 Symptom | 0.44‡ | 0.65‡ | 0.69‡ |
WURSS-21 Function | 0.45‡ | 0.61‡ | 0.61‡ |
Investigator’s End-of-Study Assessment | −0.04 | −0.20† | −0.37‡ |