Drooling or sialorrhea refers to an unintentional loss of saliva and other oral contents from the mouth. Although drooling may be encountered in healthy children, but beyond the age of 3 years is considered abnormal. Uncontrolled sialorrhoea can have negative consequences on health and quality of life.
Since the 1990s, glycopyrronium has been used for the management of sialorrhoea (drooling) in children with impaired central nervous system, such as cerebral palsy, due to its interfering action on saliva production. However, the effectiveness of glycopyrronium bromide should be balanced against the adverse effects associated with treatment.
The Marketing Authorization applicant has been asked by the Medicines and Healthcare products Regulatory Agency (MHRA) to provide additional safety information on prescribing of glycopyrronium bromide as part of the licensing application for the management of severe sialorrhoea (chronic pathological drooling) in children aged 3-17 years.
This study will use the information from the CPRD to investigate the safety profile of oral glycopyrronium bromide in children aged between 3-17 years.
In the context of the glycopyrronium Bromide (1mg/5mL) oral solution marketing authorization application, the MHRA recommended additional information to support safety profile of drug in children. In response to this, the Company (Ennogen Healthcare Ltd.) will conduct a retrospective observational study using CPRD data.
This descriptive study will help the applicant to show that glycopyrronium bromide is a safe medicine for treating severe drooling of saliva in children and adolescents (aged 3-17 years) with conditions affecting the nervous system, such as cerebral palsy and neurogenerative disease.
The study aims to analyse the CPRD data and understand the safety profile of oral glycopyrronium bromide in children aged 3-17 years. The study will mainly focus on any adverse drug events related to drug interactions, anticholinergic, cardiovascular, central nervous system, hepatic and renal effects of oral glycopyrronium bromide.
A descriptive, exploratory statistical analysis will be used to analyse the data, and is generally limited to frequency and incidence rates. The Applicant will consider the correlation and relatedness between glycopyrronium bromide exposure and adverse events. Adverse events frequency and incidence rates will be calculated for each adverse event from the total number of patients who have been exposed to oral glycopyrronium bromide. The frequency of most common adverse events per SOC will be calculated and will be presented in tabular format and graphs. Similarly, severe adverse events and drug-drug interactions relevant for glycopyrronium in general will also be considered. This study will support benefit and risk of the product in regards to its risk and other common and rare adverse events that may have occurred with exposure with glycopyrronium bromide. This will also help healthcare professionals in adequately managing and monitoring of patients in respect to dosing and in further treatment.
· To understand the safety profile of glycopyrronium bromide in children aged 3-17 years.
Glycopyrronium bromide is a medication of the muscarinic anticholinergic group. Most common adverse events of antimuscarinics agents include constipation, dizziness, drowsiness, dry mouth, dyspepsia, flushing, headache, nausea, palpitations, skin reactions, tachycardia, urinary disorders, vision disorders, and vomiting. Additionally, angioedema and confusion are reported rare or very rarely for these class of drugs.
Hence specific outcomes of interest will include:
Cardiovascular System (CVS) effects including cardiac dysrhythmia, abnormal ECG
Central Nervous System (CNS) effects including headache, confusion, restlessness, flushing, pyrexia, frustration, dizziness, abnormal behaviour and drowsiness
Gastrointestinal effects including constipation, dry mouth, nausea, vomiting, diarrhoea, diarrhoea symptom and dyspepsia
Hepatic and renal effects including at risk for impaired liver function, liver enzyme abnormal, urinary retention
Respiratory effects including nasal congestion and pneumonia
Vision disorders including blurred vision
Angioedema
Drug interactions
Drug overdose
Use in patients with renal impairment
All adverse events associated with the use of glycopyrronium bromide (including specific outcomes of interest) in the described population will be reviewed as described in Section O (Statistical analysis).
Bhavin Kalola - Chief Investigator - Ennogen
Pipasha Biswas - Corresponding Applicant - Symogen
Bhanu Rudra - Collaborator - Symogen