Safety and Efficacy Study of Oral Glycopyrrolate Liquid for the Treatment of Pathologic (Chronic Moderate to Severe) Drooling in Pediatric Patients 3 to 18 Years of Age With Cerebral Palsy or Other Neurologic Conditions

A Six-Month, Multi-Center, Open-Label Study to Assess the Safety and Efficacy of Oral Glycopyrrolate Liquid for the Treatment of Pathologic (Chronic Moderate to Severe) Drooling in Pediatric Patients 3 to 18 Years of Age With Cerebral Palsy or Other Neurologic Conditions

This is an open-label clinical research study of an oral glycopyrrolate liquid for the treatment of chronic moderate to severe drooling in patients with cerebral palsy or other neurological conditions. Patients participating in the study will receive oral glycopyrrolate liquid (1 mg/5 ml) three times a day (TID) for study duration of 24 weeks. After a washout, screening, and 2-day baseline period, patients will be enrolled in a 4-week dose titration period. Glycopyrrolate liquid doses will be titrated using dose levels in the Dose Titration Schedule. Titration will begin at 0.02 mg/kg per dose TID and sequentially increased in 0.02 mg/kg per dose increments TID every 5-7 days during the first four weeks until optimal individualized response is obtained for each patient or a maximum dose of 0.1 mg/kg TID is reached, not exceeding 3 mg TID or Dose-level 5 in the Dose Titration Schedule, whichever is lesser. Optimal dose for each patient is the dose at which he/she is receiving the maximum benefit from the study drug (greatest improvement in drooling) while experiencing minimum side effects. All patients will receive close attention by study staff throughout the study.

Inclusion Criteria:

To be included in this study, patients must meet the following criteria:

• Male or female, weighing at least 13 kilograms (27 pounds), aged 3 through 18 years
• Diagnosis of cerebral palsy and/or mental retardation or any other neurologic impairment or condition (cognitively capable and cognitively impaired patients may be enrolled)
• Chronic drooling in the absence of treatment to the extent that the chin or clothing becomes wet on most days by confirming the Modified Teacher's Drooling Scale score ≥ 5
• Must be living in a situation where reliable parents/caregivers are willing and capable of administering medications, as determined by the investigator
• Written informed consent signed by the parent or legally acceptable representative
• Written assent signed by the age-appropriate patient if mentally capable, as determined by the investigator, and required by the site's Institutional Review Board
• If female of childbearing potential, the patient must have a negative pregnancy test at screening and Visit 2
• If female of childbearing potential and sexually active, she must use a medically acceptable form of contraception

Exclusion Criteria:

Patients are excluded from this study if they meet any of the following criteria:

• Patients who used glycopyrrolate within approximately 24 hours prior to the start of the baseline period, which began on Day -2
• Patients who used prohibited medications within 5 plasma half-lives of the medication prior to the start of the baseline period
• Patients injected with intrasalivary gland botulinum toxin within 10 months prior to the start of the baseline period
• Patients using intraoral devices or prosthetics for the treatment of drooling within 1 week prior to the start of the baseline period
• Patients receiving acupuncture for the treatment of drooling or who have received acupuncture for the treatment of drooling within 3 months prior to the start of the baseline period
• Patients who have medical conditions contraindicating anticholinergic therapy including gastrointestinal reflux, narrow-angle glaucoma, obstructive uropathy, obstructive disease of the gastrointestinal tract (i.e., delayed gastric emptying, pyloroduodenal stenosis, etc.), paralytic ileus, intestinal atony, vesicoureteral reflux, reactive airway disease, myasthenia gravis, hyperthyroidism, cardiac arrhythmias and/or tachycardia, and/or clinically significant electrocardiogram abnormalities, as determined by the investigator
• Patients who have a known contraindication to the study medication, including allergy to the study medication or any of its components
• Patients who have poorly controlled seizures defined as daily seizures
• Patients who have a history of obstructive disease of the gastrointestinal tract (i.e., intestinal obstruction)
• Patients who have clinically significant hepatic or renal impairment, at the discretion of the investigator
• Patients who are pregnant or breastfeeding
• Patients who have received any investigational drugs within 30 days of study entry
• Patient, families, or parents/caregivers who are expected to be non-compliant with the study procedures, as judged by the investigator
• Patients who are unable to meet the requirements of the study for any reason, as determined by the investigator
• Patients who have unstable mental disease, as determined by the investigator