Antitussive Effect of a Naturally Flavored Syrup Containing Diphenhydramine, Compared With Dextromethorphan and Placebo

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the antitussive (cough-suppressing) effects of two liquid medications: a combination of diphenhydramine and phenylephrine in a naturally cocoa flavoring, and, dextromethorphan syrup, compared with placebo.

Official Title
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Antitussive Effect of a Naturally Flavored, Multi-Component Syrup Containing Diphenhydramine, Compared With Dextromethorphan and Placebo

Conditions
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Cough Reflex Sensitivity

Intervention / Treatment
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* Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo
* Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan
* Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo
* Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa
* Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan
* Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy adult nonsmokers onset of acute, viral upper respiratory tract infection (common cold) within 72 hours of enrollment Exclusion Criteria: smokers history of asthma or other respiratory disorders

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A, B, then C<br>Subjects received the following: Period 1: single oral dose of diphenhydramine 25 mg and phenylephrine 10 mg, in naturally-flavored cocoa syrup (treatment A). Period 2: dextromethorphan syrup 30 mg (treatment B); Period 3: placebo liquid, dextrose in water, 20 mL (treatment C). Intervention: capsaicin cough challenge testing 2 hours after study drug ingestion.Each dosing period separated by 1-2 day washout period. | Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo<br>* diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; placebo.<br>Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan<br>* diphenhydramine 25 mg and phenylephrine 10 mg; placebo; dextromethorphan 30 mg.<br>Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo<br>* dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg; placebo<br>Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa<br>* dextromethorphan 30 mg; placebo; diphenhydramine 25 mg and phenylephrine 10 mg<br>Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan<br>* placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg<br>Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa<br>* placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg<br>|
| Experimental: A, C, then B<br>Subjects received the following: Period 1: single oral doce of diphenhydramine 25 mg and phenylephrine 10 mg, in naturally-flavored cocoa syrup (treatment A); Period 2: placebo liquid, dextrose in watwer, 20 mL (treatment C); Period 3: dextromethorphan syrup 30 mg (treatment B). Intervention: capsaicin cough challenge testing 2 hours after study drug ingestion.Each dosing period separated by 1-2 day washout period. | Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo<br>* diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; placebo.<br>Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan<br>* diphenhydramine 25 mg and phenylephrine 10 mg; placebo; dextromethorphan 30 mg.<br>Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo<br>* dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg; placebo<br>Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa<br>* dextromethorphan 30 mg; placebo; diphenhydramine 25 mg and phenylephrine 10 mg<br>Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan<br>* placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg<br>Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa<br>* placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg<br>|
| Experimental: B, A, then C<br>Subjects received the following: Period 1: dextromethorphan syrup 30 mg (treatment B); Period 2: single dose of oral diphenhydramine 25 mg and phenylephrine 10 mg, in a naturally-flavored cocoa syrup (treatment A); Period 3: placebo liquid, dextrose in water, 20 mL (treatment C). Intervention: capsaicin cough challenge testing 2 hours after study drug ingestion. Each dosing period separated by 1-2 day washout period. | Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo<br>* diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; placebo.<br>Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan<br>* diphenhydramine 25 mg and phenylephrine 10 mg; placebo; dextromethorphan 30 mg.<br>Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo<br>* dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg; placebo<br>Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa<br>* dextromethorphan 30 mg; placebo; diphenhydramine 25 mg and phenylephrine 10 mg<br>Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan<br>* placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg<br>Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa<br>* placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg<br>|
| Experimental: B, C, then A<br>Subjects received the following: Period 1: dextromethorphan 30 mg syrup (treatment B); Period 2: placebo liquid, dextrose in water, 20 mL (treatment C); Period 3: single dose of oral diphenhydramine 25 mg and phenylephrine 10 mg in a naturally-flavored cocoa syrup (treatment A). Intervention: capsaicin cough challenge testing 2 hours after study drug ingestion. Each dosing period separated by 1-2 day washout period. | Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo<br>* diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; placebo.<br>Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan<br>* diphenhydramine 25 mg and phenylephrine 10 mg; placebo; dextromethorphan 30 mg.<br>Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo<br>* dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg; placebo<br>Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa<br>* dextromethorphan 30 mg; placebo; diphenhydramine 25 mg and phenylephrine 10 mg<br>Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan<br>* placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg<br>Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa<br>* placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg<br>|
| Experimental: C, A, then B<br>Subjects received the following: Period 1: placebo liquid, dextrose in water, 20 mL (treatment C); Period 2: a single oral dose of diphenhydramine 25 mg and phenylephrine 10 mg in a naturally-flavored cocoa syrup (treatment A); Period 3: dextromethorphan 30 mg syrup (treatment B). Intervention: capsaicin cough challenge testing 2 hours after study drug ingestion. Each dosing period separated by 1-2 day washout period. | Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo<br>* diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; placebo.<br>Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan<br>* diphenhydramine 25 mg and phenylephrine 10 mg; placebo; dextromethorphan 30 mg.<br>Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo<br>* dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg; placebo<br>Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa<br>* dextromethorphan 30 mg; placebo; diphenhydramine 25 mg and phenylephrine 10 mg<br>Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan<br>* placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg<br>Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa<br>* placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg<br>|
| Experimental: C, B, then A<br>Subjects received the following: Period 1: placebo liquid, dextrose in water, 20 mL (treatment C); Period 2: dextromethorphan 30 mg syrup (treatment B); Period 3: a single oral dose of diphenhydramine 25 mg and phenylephrine 10 mg in a naturally-flavored cocoa syrup (treatment A). Intervention: capsaicin cough challenge testing 2 hours after study drug ingestion. Each dosing period separated by 1-2 day washout period. | Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo<br>* diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; placebo.<br>Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan<br>* diphenhydramine 25 mg and phenylephrine 10 mg; placebo; dextromethorphan 30 mg.<br>Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo<br>* dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg; placebo<br>Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa<br>* dextromethorphan 30 mg; placebo; diphenhydramine 25 mg and phenylephrine 10 mg<br>Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan<br>* placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg<br>Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa<br>* placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cough Reflex Sensitivity to Capsaicin | increase in C5 (decrease in cough reflex sensitivity). Capsaicin cough challenge involves subjects breathing in incremental doubling concentrations of aerosolized capsaicin, 1 minute apart, until the concentration of capsaicin (micromolar) inducing 5 or more coughs (C5) is reached. | 2 hours after study drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cough, cough reflex, capsaicin, diphenhydramine, phenylephrine, dextromethorphan, placebo