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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Common Cold

Intervention / Treatment
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* Drug: Acetylcystine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2% Acetylcystine Solution<br>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<br>* Clear oral solution containing 2% acetylcysteine (g/mL) in a 100 mL amber glass bottle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Onset of Warming Sensation | 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. | 10 minutes post-dose | 
| Duration of Warming Sensation | 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 | 10 minutes post-dose | 
| Warming Sensation Intensity at Pre-Dose and 60 Sec (Seconds) 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. | Pre-dose and 60 sec post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Acceptability of Warming Sensation | 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 | 10 minutes post-dose | 
| Number of Participants With Overall Opinion of Warming Sensation | 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 | 10 minutes post-dose | 
| Number of Participants With Overall Opinion of Oral Solution | Overall opinion of oral solution was measured by scale: 4 = Excellent; 3 = Good; 2 = Fair; 1 = Poor; 0 = Unacceptable. | 1 hour post-dose | 
| Local Oral Tolerability | 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. | Day 1 (at screening and end of study) |