Warming Sensation and Tolerability Study of Acetylcysteine 2% Oral Solution for Productive Cough

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02822287
• Collaborator: (none)
• Enrollment: 58
• Location: 1
• Arm: 1
• Duration (Days): 29
• Patients Per Site Per Month: 60.9

Study Details

Study Description

Brief Summary

This is a 1-treatment arm, open label design. This 1-day study includes a screening on day of attendance at clinic, followed by a washout period of 30 minutes to 8 hours (if participants are eligible for dosing the same day). The study also includes a supervised dosing with 10 mL oral solution and a 1 hour in-clinic evaluation period.

Condition or Disease	Intervention/Treatment	Phase
Common Cold	Drug: Acetylcystine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Study to Assess the Warming Sensation, Acceptability and Local Oral Tolerability of NCH-GSK Acetylcysteine 2% Oral Solution, Given as a Single Dose in Subjects Suffering From Productive Cough Due to Upper Respiratory Tract Infection
• Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 2% Acetylcystine Solution Participants will be orally administered with the clear oral solution containing 2% acetylcysteine (g/mL) in a 100 mL amber glass bottle over 1 minute or less using an oral syringe.	Drug: Acetylcystine; Clear oral solution containing 2% acetylcysteine (g/mL) in a 100 mL amber glass bottle.

Outcome Measures

Primary Outcome Measures

1. Onset of Warming Sensation [10 minutes post-dose]

   Onset and duration of action of warming sensation was measured by two stop watches started when the participants took the oral solution. First watch was stopped at the start of warming sensation and the second watch was stopped at the end. If onset had not occurred by 10 minutes then time to onset was censored at 10 minutes. 53 of the 57 participants had onset within 10 minutes after dosing.

2. Duration of Warming Sensation [10 minutes post-dose]

   Duration of action of warming sensation was measured by two stop watches started when the participants took the oral solution. First watch was stopped at the start of warming sensation and the second watch was stopped at the end. If onset of warming sensation occurred within 10 minutes of dosing but had not ended by the end of 10 minutes following dosing, then the duration was censored at 10 minutes minus the time to onset

3. Warming Sensation Intensity at Pre-Dose and 60 Sec (Seconds) Post-Dose [Pre-dose and 60 sec post-dose]

   Warming Sensation Intensity was measured on 100 mm visual analogue scale (VAS), marked as "no warming sensation" on the left hand side (= 0 mm) and "strongest possible warming sensation" at the right hand side (=100 mm) at pre-dose.

Secondary Outcome Measures

1. Number of Participants With Acceptability of Warming Sensation [10 minutes post-dose]

   Acceptability of strength of warming sensation was measured by a scale: 5= Much too strong; 4=Too strong (too warming); 3= Just about right (pleasant warming); 2= Too weak (not warming enough); 1= Much too weak

2. Number of Participants With Overall Opinion of Warming Sensation [10 minutes post-dose]

   Overall opinion of warming sensation was measured by scale: 9= Like extremely; 8= Like very much; 7= Like moderately; 6= Like slightly; 5= Neither like nor dislike; 4= Dislike slightly; 3= Dislike moderately; 2= Dislike very much; 1= Dislike extremely

3. Number of Participants With Overall Opinion of Oral Solution [1 hour post-dose]

   Overall opinion of oral solution was measured by scale: 4 = Excellent; 3 = Good; 2 = Fair; 1 = Poor; 0 = Unacceptable.

4. Local Oral Tolerability [Day 1 (at screening and end of study)]

   Local oral tolerability was assessed by performing oropharyngeal examination as follows: Results of oropharyngeal examination (Normal and abnormal); If abnormal, any signs of lesion on oral mucosa or irritation of oral mucosa.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants must give written informed consent before any assessment is performed. In the case of adolescents Informed Consent must be signed by one or both parents or legal guardian as per local regulations and an Informed Assent must be signed by the participant.

• Must be males or females ≥ 12 years.

• Willingness and ability to communicate, to comply with all study requirements and to complete the study.

• Productive cough of less than 7 days duration, rated based on interview with the participant as mild to moderate severity on a four- point ordinal scale (not present, mild, moderate, severe) due to upper respiratory tract infection.

Exclusion Criteria:

• Use of other investigational drugs before enrollment, or within 30 days or 5 half-lives before enrollment, whichever is longer.

• Pre-dose productive cough or sore throat rated as severe on a four-point ordinal scale (not present, mild, moderate, severe) based on interview with the participant.

• Pre-dose temperature equal or above 39.4°C at screening measured by oral thermometer.

• History of hypersensitivity to any of the study drugs and the listed excipients or to drugs of similar chemical classes.

• Pregnant , nursing (lactating women) or women with child bearing potential UNLESS they are using effective methods of contraception.

• Use of any medication for sore throat containing a local anaesthetic, methanol or any topical products containing menthol, peppermint, spearmint or within the 6 hours prior to dosing.

• Use of any paracetamol, non-steroidal anti-inflammatory drug (NSAID) or any oral/nasal decongestant within 6 hours prior to dosing.

• Use of substances of abuse, herbal medications, or antihistamines within 48 hours of dosing.

• Hepatic or severe renal impairment, hypertension, hyperthyroidism, diabetes, or heart disease.

• Drinking of tea, coffee or other caffeinated beverages 1 hour prior to dosing.

• Drinking of any hot beverages 1 hour prior to dosing.

• Participant is a current smoker of ≥10 cigarettes per day (or reports equivalent smoking habits using other tobacco products) or smoked or chewed tobacco products within 12 hours before dosing.

• Participant is taking nitroglycerin and nitrate drug treatments.

• Participants who took antibiotic treatments such as semisynthetic penicillins, tetracyclines, cephalosporins and aminoglycosides within 2 hours of dosing. Amoxicillin, doxycycline, erythromycin, thiamphenicol and cefuroxime are allowed without this restriction.

• Participants with gastroduodenal (peptic) ulcers, asthma.

• Participants with intolerance to histamines.

• Participants who have used antitussives (e.g., dextromethorphan, codeine), anticholinergic drugs (atropine-like) within the past 24 hours.

• Participants who have taken heavy metal salts such as calcium, gold and iron within 2 hours of enrollment.

• A history of alcohol abuse or an admission by the participant that they regularly consume alcohol in excess of the recommended weekly limits of 21 units for females and 28 units for males.

• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Erfurt	Thueringen	Germany	99084

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02822287
• Other Study ID Numbers: 205034
• First Posted: Jul 4, 2016
• Last Update Posted: Jan 31, 2017
• Last Verified: Sep 1, 2016

• Additional relevant MeSH terms: Common Cold

Study Results

Participant Flow

Recruitment Details	Participant were recruited at 1 center in Germany
Pre-assignment Detail	A total of 58 potential participants were screened and 57 participants were included in the study. All 57 participants received the investigational product.

Arm/Group Title	2% Acetylcystine Solution
Arm/Group Description	Participants received a single dose of 200 mg (10 mL) of Acetylcysteine 2% oral solution.
Period Title: Overall Study
STARTED	57
COMPLETED	57
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	2% Acetylcystine Solution
Arm/Group Description	Participants received a single dose of 200 mg (10 mL) of Acetylcysteine 2% oral solution.
Overall Participants	57
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	38.7 (13.88)
Gender (Count of Participants)
Female	33 57.9%
Male	24 42.1%

Outcome Measures

1. Primary Outcome

Title	Onset of Warming Sensation
Description	Onset and duration of action of warming sensation was measured by two stop watches started when the participants took the oral solution. First watch was stopped at the start of warming sensation and the second watch was stopped at the end. If onset had not occurred by 10 minutes then time to onset was censored at 10 minutes. 53 of the 57 participants had onset within 10 minutes after dosing.
Time Frame	10 minutes post-dose

Outcome Measure Data

Analysis Population Description

The Safety Population was defined as all treated subjects, i.e., all subjects who received any dose of study drug. The Safety Population was the primary population for both the primary and secondary endpoint analyses and the safety analysis.

Arm/Group Title	2% Acetylcystine Solution
Arm/Group Description	Participants received a single dose of 200 mg (10 mL) of Acetylcysteine 2% oral solution.
Measure Participants	57
Median (Full Range) [Minutes]	0.233

2. Primary Outcome

Title	Duration of Warming Sensation
Description	Duration of action of warming sensation was measured by two stop watches started when the participants took the oral solution. First watch was stopped at the start of warming sensation and the second watch was stopped at the end. If onset of warming sensation occurred within 10 minutes of dosing but had not ended by the end of 10 minutes following dosing, then the duration was censored at 10 minutes minus the time to onset
Time Frame	10 minutes post-dose

Outcome Measure Data

Analysis Population Description

The safety Population was defined as all treated subjects, i.e., all subjects who received any dose of study drug. The Safety Population was the primary population for both the primary and secondary endpoint and safety analysis. Of the 57 subjects in the Safety Population, 53 reported an onset of a warming sensation within10 minutes after dosing.

Arm/Group Title	2% Acetylcystine Solution
Arm/Group Description	Participants received a single dose of 200 mg (10 mL) of Acetylcysteine 2% oral solution.
Measure Participants	53
Median (Full Range) [Minutes]	2.833

3. Primary Outcome

Title	Warming Sensation Intensity at Pre-Dose and 60 Sec (Seconds) Post-Dose
Description	Warming Sensation Intensity was measured on 100 mm visual analogue scale (VAS), marked as "no warming sensation" on the left hand side (= 0 mm) and "strongest possible warming sensation" at the right hand side (=100 mm) at pre-dose.
Time Frame	Pre-dose and 60 sec post-dose

Outcome Measure Data

Analysis Population Description

The Safety Population was defined as all treated subjects, i.e., all subjects who received any dose of study drug. The Safety Population was the primary population for both the primary and secondary endpoint analyses and the safety analysis.

Arm/Group Title	2% Acetylcystine Solution
Arm/Group Description	Participants received a single dose of 200 mg (10 mL) of Acetylcysteine 2% oral solution.
Measure Participants	57
Pre-dose	6.8 (8.69)
Post-dose (Observed)	36.1 (26.93)
Post-dose (Change)	29.2 (27.84)

4. Secondary Outcome

Title	Number of Participants With Acceptability of Warming Sensation
Description	Acceptability of strength of warming sensation was measured by a scale: 5= Much too strong; 4=Too strong (too warming); 3= Just about right (pleasant warming); 2= Too weak (not warming enough); 1= Much too weak
Time Frame	10 minutes post-dose

Outcome Measure Data

Analysis Population Description

The Safety Population was defined as all treated subjects, i.e., all subjects who received any dose of study drug. The Safety Population was the primary population for both the primary and secondary endpoint analyses and the safety analysis.

Arm/Group Title	2% Acetylcystine Solution
Arm/Group Description	Participants received a single dose of 200 mg (10 mL) of Acetylcysteine 2% oral solution.
Measure Participants	57
Much too strong	0 0%
Too strong	2 3.5%
Just about right	30 52.6%
Too Weak	16 28.1%
Much too weak	9 15.8%

5. Secondary Outcome

Title	Number of Participants With Overall Opinion of Warming Sensation
Description	Overall opinion of warming sensation was measured by scale: 9= Like extremely; 8= Like very much; 7= Like moderately; 6= Like slightly; 5= Neither like nor dislike; 4= Dislike slightly; 3= Dislike moderately; 2= Dislike very much; 1= Dislike extremely
Time Frame	10 minutes post-dose

Outcome Measure Data

Analysis Population Description

The Safety Population was defined as all treated subjects, i.e., all subjects who received any dose of study drug. The Safety Population was the primary population for both the primary and secondary endpoint analyses and the safety analysis.

Arm/Group Title	2% Acetylcystine Solution
Arm/Group Description	Participants received a single dose of 200 mg (10 mL) of Acetylcysteine 2% oral solution.
Measure Participants	57
Like extremely	1 1.8%
Like very Much	21 36.8%
Like moderately	11 19.3%
Like slightly	7 12.3%
Neither Like nor Dislike	10 17.5%
Dislike slightly	3 5.3%
Dislike Moderately	1 1.8%
Dislike Very Much	3 5.3%
Dislike extremely	0 0%

6. Secondary Outcome

Title	Number of Participants With Overall Opinion of Oral Solution
Description	Overall opinion of oral solution was measured by scale: 4 = Excellent; 3 = Good; 2 = Fair; 1 = Poor; 0 = Unacceptable.
Time Frame	1 hour post-dose

Outcome Measure Data

Analysis Population Description

The Safety Population was defined as all treated subjects, i.e., all subjects who received any dose of study drug. The Safety Population was the primary population for both the primary and secondary endpoint analyses and the safety analysis.

Arm/Group Title	2% Acetylcystine Solution
Arm/Group Description	Participants received a single dose of 200 mg (10 mL) of Acetylcysteine 2% oral solution.
Measure Participants	57
Excellent	2 3.5%
Good	21 36.8%
Fair	29 50.9%
Poor	5 8.8%
Unacceptable	0 0%

7. Secondary Outcome

Title	Local Oral Tolerability
Description	Local oral tolerability was assessed by performing oropharyngeal examination as follows: Results of oropharyngeal examination (Normal and abnormal); If abnormal, any signs of lesion on oral mucosa or irritation of oral mucosa.
Time Frame	Day 1 (at screening and end of study)

Outcome Measure Data

Analysis Population Description

The Safety Population was defined as all treated subjects, i.e., all subjects who received any dose of study drug. The Safety Population was the primary population for both the primary and secondary endpoint analyses and the safety analysis.

Arm/Group Title	2% Acetylcystine Solution
Arm/Group Description	Participants received a single dose of 200 mg (10 mL) of Acetylcysteine 2% oral solution.
Measure Participants	57
Oropharyngeal examination at screening (Normal)	52 91.2%
Oropharyngeal examination at study end (Normal)	52 91.2%
Oropharyngeal examination at screening (Abnormal)	5 8.8%
Oropharyngeal examination at study end (Abnormal)	5 8.8%
Abnormal (lesions on oral mucosa)	0 0%
Abnormal (No lesions on oral mucosa)	5 8.8%
Abnormal (Irritation of oral Mucosa)	0 0%
Abnormal (No irritation of oral Mucosa)	5 8.8%

Adverse Events

Arm/Group Title	2% Acetylcystine Solution
Arm/Group Description	Participants received a single dose of 200 mg (10 mL) of Acetylcysteine 2% oral solution.
All Cause Mortality
	2% Acetylcystine Solution
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	2% Acetylcystine Solution
	Affected / at Risk (%)	# Events
Total	0/57 (0%)
Other (Not Including Serious) Adverse Events
	2% Acetylcystine Solution
	Affected / at Risk (%)	# Events
Total	0/57 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.