Dextromethorphan Pediatric Acute Cough Study

This is a placebo-controlled, double-blind, randomized, parallel group pilot study in
approximately 150 subjects to evaluate the efficacy of dextromethorphan hydrobromide DXM) on
acute cough in a pediatric population. Subjects will be otherwise healthy males and females
aged 6-11 inclusive who are experiencing acute cough as a symptom of common cold or upper
respiratory tract infection. Subjects must have had onset of symptoms within 3 days of
screening and qualify based on physical exam and symptom questionnaire. Eligible subjects
will be given a single-blind placebo, and fitted with a cough counting device for a 2 hour
run-in period. Qualifying subjects will be stratified by age and then randomized to either
DXM or placebo in a 1:1 ratio and fitted with the cough recording device for the first 24
hours of treatment. Subjects will receive approximately 9 doses of investigational product
over the course of the 4 day study and will complete patient reported outcome questions
before the morning and afternoon doses. Subjects will return to the study site on Day 2 to
remove the cough recorder and Day 4 (+2 days) to complete the final visit. A review of any
reported adverse events will also be completed. Validated Patient Reported Outcomes (PRO)
used in the study include morning cough assessment, afternoon cough assessment, Child Global
Question, and Child Cold Symptom Checklist

Inclusion Criteria:

- Generally healthy male or female children/adolescents ages 6 to 11 years, inclusive.

- Subject has an acute cough and other symptoms consistent with a common cold/acute
upper respiratory tract infection (URTI) diagnosis as deemed by the investigator or
qualified designee based on findings from medical history review, full physical
examination and vital signs.

- The onset of symptoms must be no more than 3 days prior to Visit 1, as determined by
the subject or parent/legally acceptable representative.

- Qualifying response on the Child Cold Symptom Checklist.

- Parent/legally acceptable representative, and subject agrees the subject will not use
any other cough or cold treatments during the study.

Exclusion Criteria:

- A subchronic, or chronic cough due to any condition other than an URTI or common cold
as established by the investigator, nurse practitioner, or physician's assistant, in
accordance with the American College of Chest Physicians' (ACCP) Guidelines for
Diagnosis and Management of Cough. Special attention should be paid to highly
prevalent conditions commonly presenting with cough such as asthma, rhinitis, or
gastroesophageal reflux disease (GERD).

- Symptoms of runny nose, stuffy nose, sore throat, or sneezing due to any condition
other than URTI or common cold (eg, seasonal or perennial allergic rhinitis,
sinusitis, strep throat, vasomotor rhinitis, etc.) as established by the investigator.

- An acute cough that occurs with excessive phlegm (mucus) or is chronic such as occurs
with smoking, asthma, bronchitis, allergies, or a gastroesophageal condition (eg, acid
reflux and GERD) or history of such a cough.

- Clinical features of a complication of the common cold during the physical examination
at screening (eg, otitis media, sinusitis, or pneumonia) with or without the need for
systematic antibiotics.

- Pneumonia (active or with a symptom-free period of <30 days), asthma (active or with a
symptom-free period of <1 year), or other significant pulmonary diseases.

- Fever greater than 39ºC (102ºF oral temperature) at the time of screening if, in the
judgment of the investigator, the individual is too ill to participate in the study or
the fever is due to reasons other than URTI.

- Signs of dehydration (as may be due to vomiting, diarrhea, or lack of fluid intake)
during the physical examination at screening.

- Diabetes or hypoglycemic disorders.

- Known contraindications to the investigational product or acetaminophen (APAP).

- Sitting blood pressure reading at or above the limits as documented in the protocol.

- Obstructive sleep apnea caused by enlarged tonsils and adenoids, low muscle tone, or
allergies.

- History of known or suspected allergy or hypersensitivity to dextromethorphan (DXM) or
APAP, or any of the non medicinal ingredients contained in the single-blind
confection, double-blind investigational products, or APAP.

- History of taking any of the specified prohibited medications or products within the
corresponding washout periods prior to taking the first dose of investigational
product.

- History of taking a medication that is sedating within the past 24 hours prior to
screening (eg sedatives, hypnotics, tranquilizers, anticonvulsants, benzodiazepines,
and clonidine).

- Subject has a sibling contemporaneously participating in this study.

Randomization Criteria:

- Subjects must complete the 2 hour ambulatory cough counting baseline run-in recording
period and must return to the study site for randomization at least 2 hours after the
recording started.

- Subjects whose equipment failed, preventing collection of cough count data for at
least 2 hours during the Baseline Run-in Period, or those who took off the device
during this period will be excluded from further study participation.

- Subjects who do not return to the study site (before 3:30 pm) in time for the
afternoon dose will not be randomized.

- Qualifying response on Child Global Question