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.

Study Overview

• Status: Completed
• Conditions: Cerebral Palsy; Sialorrhea; Mental Retardation; Neurological Conditions
• Intervention / Treatment: Drug: Oral Glycopyrrolate Liquid

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Lakewood, Colorado, United States, 80214
      • Rocky Mountain Pediatrics
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Child Neurology Associates, PC
  • New York
    • Bayside, New York, United States, 11360
      • St. Mary's for Children
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron's Childrens
    • Mantua, Ohio, United States, 44255
      • Hattie Larltham Center for Children with Disabilities
  • Oklahoma
    • Bethany, Oklahoma, United States, 73008
      • The Children's Center
  • Texas
    • San Antonio, Texas, United States, 78258
      • Alamo City Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients with Chronic Drooling; Arm receiving study drug	Drug: Oral Glycopyrrolate Liquid; Study medication is administered three times a day at 7-8 AM, 1-2 PM, and 7-8 PM by the parent/caregiver

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Responders According to the Modified Teacher's Drooling Scale (mTDS)	The primary efficacy variable was patient's response status using the change from baseline to Week 24 evaluations of the mTDS assessment. Each patient was classified as a responder or non-responder according to the change in their mean mTDS rating from baseline to Week 24. Responders were patients who had at least a 3-point decrease in mTDS rating from baseline	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parent/Caregiver's Assessment of the Extent of Drooling Using Visual Analog Scale (VAS)	Parents/caregivers were to complete a 10 cm "Parent/Caregiver's Assessment of Extent of Drooling for the Day" VAS assessment (0 = normal; 10 = extremely wet) to provide an overall assessment of the extent of drooling for that day.	Baseline
Parent/Caregiver's Assessment of the Extent of Drooling Using VAS	Parents/caregivers were to complete a 10 cm "Parent/Caregiver's Assessment of Extent of Drooling for the Day" VAS assessment (0 = normal; 10 = extremely wet) to provide an overall assessment of the extent of drooling for that day.	Week 24
Parent/Caregiver's Global Assessment of Treatment	The parent/caregiver performed an overall evaluation of glycopyrrolate liquid for the treatment of drooling, benefits, and side effects over the duration of the study. The parent/caregiver selected one of the following choices to assess if 'This is a worthwhile treatment': 1 = strongly agree, 2 = agree, 3 = neutral, 4 = disagree, 5 = strongly disagree. A dichotomous global assessment was also performed and summarized with the categories 'responder' (strongly agree and agree responses aggregated) and 'non-responder'(neutral, disagree, and strongly disagree responses aggregated)	Week 24
Investigator's Global Assessment of Treatment	The investigator performed an overall evaluation of glycopyrrolate liquid for the treatment of drooling, benefits, and side effects over the duration of the study. The investigator selected one of the following choices to assess if 'This is a worthwhile treatment': 1 = strongly agree, 2 = agree, 3 = neutral, 4 = disagree, 5 = strongly disagree. A dichotomous global assessment was also performed and summarized with the categories 'responder' (strongly agree and agree responses aggregated) and 'non-responder' (neutral, disagree, and strongly disagree responses aggregated)	Week 24

Collaborators and Investigators

• Sponsor: Shionogi

Publications and helpful links

General Publications

• Zeller RS, Lee HM, Cavanaugh PF, Davidson J. Randomized Phase III evaluation of the efficacy and safety of a novel glycopyrrolate oral solution for the management of chronic severe drooling in children with cerebral palsy or other neurologic conditions. Ther Clin Risk Manag. 2012;8:15-23. doi: 10.2147/TCRM.S26893. Epub 2012 Jan 25.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: June 22, 2007
• First Submitted That Met QC Criteria: June 25, 2007
• First Posted (Estimate): June 26, 2007

Study Record Updates

• Last Update Posted (Estimate): July 9, 2012
• Last Update Submitted That Met QC Criteria: June 5, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Cerebral Palsy; Mental Retardation; Drooling; Neurological Impairment; Neurological Conditions
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Brain Damage, Chronic; Stomatognathic Diseases; Mouth Diseases; Neurodevelopmental Disorders; Salivary Gland Diseases; Cerebral Palsy; Disease; Paralysis; Intellectual Disability; Sialorrhea; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Glycopyrrolate
• Other Study ID Numbers: Sc-GLYCO-06-01