Trial Outcomes & Findings for 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 (NCT NCT00491894)

Last Updated: 2012-07-09

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

137 participants

Primary outcome timeframe

6 months

Results posted on

2012-07-09

Participant Flow

First patient was enrolled on April 03, 2007 and last patient completed on May 30, 2008

After a washout and screening period, and 2-day baseline period, patients were enrolled in a 4-week dose titration period which commenced with the goal of identifying an optimal 3 times daily maintenance dose for each patient. The resulting individualized optimal maintenance dose was to be administered for the remainder of the 24-week study

Participant milestones

Participant milestones
Measure	Patients With Chronic Drooling A 4-week dose titration period until an optimal individualized response was obtained for each patient or a maximum dose of 0.1 mg/kg/dose was reached. Doses were not to exceed 3.0 mg/kg TID
Overall Study STARTED	137
Overall Study COMPLETED	103
Overall Study NOT COMPLETED	34

Reasons for withdrawal

Reasons for withdrawal
Measure	Patients With Chronic Drooling A 4-week dose titration period until an optimal individualized response was obtained for each patient or a maximum dose of 0.1 mg/kg/dose was reached. Doses were not to exceed 3.0 mg/kg TID
Overall Study Adverse Event	14
Overall Study Withdrawal by Subject	5
Overall Study Death	3
Overall Study Lost to Follow-up	3
Overall Study Lack of Efficacy	2
Overall Study Other-Failed to meet any criteria	2
Overall Study Physician Decision	2
Overall Study Protocol Violation	2
Overall Study Other-Intake of prohibited medication	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Patients With Chronic Drooling n=137 Participants A 4-week dose titration period until an optimal individualized response was obtained for each patient or a maximum dose of 0.1 mg/kg/dose was reached. Doses were not to exceed 3.0 mg/kg TID
Age, Categorical <=18 years	137 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	11.0 years STANDARD_DEVIATION 4.35 • n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants
Sex: Female, Male Male	77 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	121 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	29 Participants n=5 Participants
Race (NIH/OMB) White	98 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: The analysis was done by intention to treat method. For purposes of statistical estimation, patients who dropped out due to lack of efficacy had their worst observation carried forward. Patients who dropped out for reasons other than lack of efficacy had their last observation carried forward

Outcome measures

Outcome measures
Measure	Patients With Chronic Drooling n=137 Participants A 4-week dose titration period until an optimal individualized response was obtained for each patient or a maximum dose of 0.1 mg/kg/dose was reached. Doses were not to exceed 3.0 mg/kg TID
Proportion of Responders According to the Modified Teacher's Drooling Scale (mTDS) Missing	7 Participants
Proportion of Responders According to the Modified Teacher's Drooling Scale (mTDS) Responders	68 Participants
Proportion of Responders According to the Modified Teacher's Drooling Scale (mTDS) Non-Responders	62 Participants

SECONDARY outcome

Timeframe: Baseline

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.

Outcome measures

Outcome measures
Measure	Patients With Chronic Drooling n=137 Participants A 4-week dose titration period until an optimal individualized response was obtained for each patient or a maximum dose of 0.1 mg/kg/dose was reached. Doses were not to exceed 3.0 mg/kg TID
Parent/Caregiver's Assessment of the Extent of Drooling Using Visual Analog Scale (VAS)	6.56 VAS score Standard Deviation 2.34

SECONDARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	Patients With Chronic Drooling n=137 Participants A 4-week dose titration period until an optimal individualized response was obtained for each patient or a maximum dose of 0.1 mg/kg/dose was reached. Doses were not to exceed 3.0 mg/kg TID
Parent/Caregiver's Assessment of the Extent of Drooling Using VAS	3.21 VAS score Standard Deviation 2.20

SECONDARY outcome

Timeframe: Week 24

Population: The analysis for parent/caregiver's Global Assessment was done by intention to treat method

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)

Outcome measures

Outcome measures
Measure	Patients With Chronic Drooling n=137 Participants A 4-week dose titration period until an optimal individualized response was obtained for each patient or a maximum dose of 0.1 mg/kg/dose was reached. Doses were not to exceed 3.0 mg/kg TID
Parent/Caregiver's Global Assessment of Treatment Responders	101 Participants
Parent/Caregiver's Global Assessment of Treatment Non-Responders	20 Participants
Parent/Caregiver's Global Assessment of Treatment Missing	16 Participants

SECONDARY outcome

Timeframe: Week 24

Population: The analysis for investigator's Global Assessment was done by intention to treat method

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)

Outcome measures

Outcome measures
Measure	Patients With Chronic Drooling n=137 Participants A 4-week dose titration period until an optimal individualized response was obtained for each patient or a maximum dose of 0.1 mg/kg/dose was reached. Doses were not to exceed 3.0 mg/kg TID
Investigator's Global Assessment of Treatment Responders	109 Participants
Investigator's Global Assessment of Treatment Non-Responders	18 Participants
Investigator's Global Assessment of Treatment Missing	10 Participants

Adverse Events

Patients With Chronic Drooling

Serious events: 14 serious events

Other events: 122 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Patients With Chronic Drooling n=137 participants at risk A 4-week dose titration period until an optimal individualized response was obtained for each patient or a maximum dose of 0.1 mg/kg/dose was reached. Doses were not to exceed 3.0 mg/kg TID
Nervous system disorders Nystagmus	0.73% 1/137 • Number of events 1 • 6 months
Nervous system disorders Convulsion	0.73% 1/137 • Number of events 1 • 6 months
Nervous system disorders Hydrocephalus	0.73% 1/137 • Number of events 1 • 6 months
Nervous system disorders Anoxic encephalopathy	0.73% 1/137 • Number of events 1 • 6 months
Infections and infestations Urinary tract infection	0.73% 1/137 • Number of events 1 • 6 months
Infections and infestations Otitis media	0.73% 1/137 • Number of events 1 • 6 months
Infections and infestations Esophageal candidiasis	0.73% 1/137 • Number of events 1 • 6 months
Infections and infestations Cellulitis	0.73% 1/137 • Number of events 1 • 6 months
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	0.73% 1/137 • Number of events 1 • 6 months
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.73% 1/137 • Number of events 1 • 6 months
Respiratory, thoracic and mediastinal disorders Aspiration	0.73% 1/137 • Number of events 1 • 6 months
Metabolism and nutrition disorders Dehydration	0.73% 1/137 • Number of events 1 • 6 months
General disorders Multi-organ failure	0.73% 1/137 • Number of events 1 • 6 months
Gastrointestinal disorders Impaired gastric emptying	0.73% 1/137 • Number of events 1 • 6 months
Gastrointestinal disorders Gastrointestinal motility disorder	0.73% 1/137 • Number of events 1 • 6 months
Injury, poisoning and procedural complications Therapeutic agent toxicity	0.73% 1/137 • Number of events 1 • 6 months
Infections and infestations Pneumonia	2.2% 3/137 • Number of events 3 • 6 months

Other adverse events

Other adverse events
Measure	Patients With Chronic Drooling n=137 participants at risk A 4-week dose titration period until an optimal individualized response was obtained for each patient or a maximum dose of 0.1 mg/kg/dose was reached. Doses were not to exceed 3.0 mg/kg TID
Gastrointestinal disorders Constipation	20.4% 28/137 • 6 months
Gastrointestinal disorders Diarrhea	17.5% 24/137 • 6 months
Gastrointestinal disorders Vomiting	17.5% 24/137 • 6 months
Gastrointestinal disorders Dry mouth	10.9% 15/137 • 6 months
Gastrointestinal disorders Lip dry	3.6% 5/137 • 6 months
Infections and infestations Otitis media	8.0% 11/137 • 6 months
Infections and infestations Urinary tract infection	7.3% 10/137 • 6 months
Infections and infestations Upper respiratory tract infection	8.0% 11/137 • 6 months
Infections and infestations Influenza	5.1% 7/137 • 6 months
Infections and infestations Pharyngitis streptococcal	5.1% 7/137 • 6 months
Infections and infestations Sinusitis	4.4% 6/137 • 6 months
Infections and infestations Gastroenteritis viral	4.4% 6/137 • 6 months
Infections and infestations Nasopharyngitis	3.6% 5/137 • 6 months
Infections and infestations Viral upper respiratory tract infection	3.6% 5/137 • 6 months
Respiratory, thoracic and mediastinal disorders Nasal congestion	10.9% 15/137 • 6 months
Respiratory, thoracic and mediastinal disorders Epistaxis	5.1% 7/137 • 6 months
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	4.4% 6/137 • 6 months
Nervous system disorders Convulsion	7.3% 10/137 • 6 months
Nervous system disorders Somnolence	5.1% 7/137 • 6 months
Nervous system disorders Headache	4.4% 6/137 • 6 months
General disorders Pyrexia	14.6% 20/137 • 6 months
General disorders Irritability	5.8% 8/137 • 6 months
Skin and subcutaneous tissue disorders Rash	8.0% 11/137 • 6 months
Injury, poisoning and procedural complications Feeding tube complication	3.6% 5/137 • 6 months
Injury, poisoning and procedural complications Procedural pain	3.6% 5/137 • 6 months
Vascular disorders Flushing	10.9% 15/137 • 6 months
Psychiatric disorders Restlessness	3.6% 5/137 • 6 months
Investigations Urine output decreased	3.6% 5/137 • 6 months
Renal and urinary disorders Dysuria	6.6% 9/137 • 6 months

Additional Information

Shionogi Clinical Trials Administrator

Shionogi USA

Phone: 800-849-9707

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can embargo results from a PI's center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 60 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.
Publication restrictions are in place

Restriction type: OTHER