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

This study has been completed.
Sponsor:
Information provided by:
Shionogi Inc.
ClinicalTrials.gov Identifier:
NCT00491894
First received: June 22, 2007
Last updated: June 5, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Cerebral Palsy
Neurological Conditions
Mental Retardation
Sialorrhea
Drug: Oral Glycopyrrolate Liquid
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Shionogi Inc.:

Primary Outcome Measures:
  • Proportion of Responders According to the Modified Teacher's Drooling Scale (mTDS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Parent/Caregiver's Assessment of the Extent of Drooling Using Visual Analog Scale (VAS) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Parent/Caregiver's Assessment of the Extent of Drooling Using VAS [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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.

  • Parent/Caregiver's Global Assessment of Treatment [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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)

  • Investigator's Global Assessment of Treatment [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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)


Enrollment: 137
Study Start Date: March 2007
Study Completion Date: June 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   3 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00491894

Locations
United States, Colorado
Rocky Mountain Pediatrics
Lakewood, Colorado, United States, 80214
United States, Georgia
Child Neurology Associates, PC
Atlanta, Georgia, United States, 30342
United States, New York
St. Mary's for Children
Bayside, New York, United States, 11360
United States, Ohio
Akron's Childrens
Akron, Ohio, United States, 44308
Hattie Larltham Center for Children with Disabilities
Mantua, Ohio, United States, 44255
United States, Oklahoma
The Children's Center
Bethany, Oklahoma, United States, 73008
United States, Texas
Alamo City Clinical Research
San Antonio, Texas, United States, 78258
Sponsors and Collaborators
Shionogi
Investigators
Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line Shionogi
  More Information

No publications provided

Responsible Party: Shionogi Clinical Trials Administrator, Shionogi
ClinicalTrials.gov Identifier: NCT00491894     History of Changes
Obsolete Identifiers: NCT00425087
Other Study ID Numbers: Sc-GLYCO-06-01
Study First Received: June 22, 2007
Results First Received: August 2, 2010
Last Updated: June 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Shionogi Inc.:
Mental Retardation
Neurological Impairment
Cerebral Palsy
Drooling
Neurological Conditions

Additional relevant MeSH terms:
Cerebral Palsy
Disease
Paralysis
Intellectual Disability
Sialorrhea
Brain Damage, Chronic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Pathologic Processes
Neurologic Manifestations
Signs and Symptoms
Neurobehavioral Manifestations
Mental Disorders Diagnosed in Childhood
Mental Disorders
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Glycopyrrolate
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014