Glycopyrroniumbromid (1) – Sialanar®

• Clinical trials
  • Zeller 2012a is a randomised, controlled, double-blind, parallel-group Phase III trial comparing glycopyrronium bromide with placebo.
  • Mier 2000 is a randomised, controlled, double-blind, crossover trial.
  • Zeller 2012b is a single-arm, open-label study.

a) In children and adolescents aged 3 years and over with chronic neurological conditions for the symptomatic treatment of severe sialorrhoea (chronic pathologically increased salivation)

• Consequently, the G-BA concludes, on the basis of the criteria set out in Section 5(7) of the AM-NutzenV, the G-BA has determined that glycopyrronium bromide offers a non-quantifiable additional benefit for the symptomatic treatment of severe sialorrhoea in children and adolescents aged 3 years and over with chronic neurological disorders, compared with placebo.
• mortality
  • No deaths occurred in the Zeller 2012a and Mier 2000 studies.
  • There is therefore no difference between the two treatment groups in terms of mortality.
• Morbidity – Modified Teacher’s Drooling Scale (mTDS)
  • The modified Teacher’s Drooling Scale (mTDS) simultaneously measures the frequency and severity of hypersalivation.
  • The study results for the mTDS endpoint from the Mier 2000 study cannot be used for the benefit assessment due to methodological uncertainties.
  • Usable data for the patient-relevant mTDS endpoint are available only from the Zeller 2012a study.
  • Both analysis strategies show a significant effect in the same direction for the mTDS endpoint in favour of glycopyrronium bromide (Hedges’ g: 1.55 [0.79; 2.30] and 1.42 [0.68; 2.16], respectively).
  • On this basis, it is not possible to estimate with sufficient certainty the extent of the advantage to the patient.
  • The result for the mTDS endpoint is therefore classified overall as non-quantifiable.
  • No further data are available for the morbidity category.
• Health-related quality of life
  • No data on health-related quality of life were collected in either the Zeller 2012a study or the Mier 2000 study.
  • Consequently, no evaluable data are available for this endpoint category.
• Side effects
  • For the patient-relevant endpoints SAE, AE and discontinuation due to AE, descriptive values for both treatment groups were reported in the Zeller 2012a study.
  • For the Mier 2000 study, no analysable data are available for the SAE endpoint, whilst high rates of AE and discontinuation due to AE were observed in the intervention group.
  • The PTs in the Zeller 2012a study, which show an absolute difference of ≥ 10 % between the two treatment groups, include side effects such as dry mouth, drowsiness and urinary retention, as well as the adverse events of vomiting, upper respiratory tract infections, nasal congestion, cough and rash.
  • With regard to the Mier 2000 study, the AEs for which an absolute difference of ≥ 10% was recorded between the two treatment groups include side effects such as constipation, excessive dryness of the mouth and secretions, urinary retention, facial flushing and behavioural changes, as well as vomiting.
  • Uncertainties remain regarding the side effects, meaning that no definitive assessment can be made overall.
• Overall assessment
  • For the benefit assessment of the active ingredient glycopyrronium bromide for the symptomatic treatment of severe sialorrhoea (chronic pathologically increased salivation) in children and adolescents aged 3 years and over with chronic neurological conditions, the results are based on 2 randomised, double-blind studies are available, in which glycopyrronium bromide was compared with placebo in children and adolescents with sialorrhoea and a chronic neurological condition.
  • With regard to the endpoint category of mortality, there is neither an advantage nor a disadvantage between the two treatment groups.
  • In the morbidity category, only one patient-relevant endpoint – salivary flow as measured by mTDS – was assessed, for which there is a statistically significant difference in favour of glycopyrronium bromide.
  • This is assessed as non-quantifiable.
  • Other patient-relevant endpoints, such as health-related quality of life, were not assessed.
  • In the ‘side effects’ category, no definitive assessment can be made overall.
  • Overall, there remains a non-quantifiable additional benefit in the morbidity category, which is not called into question by results in other endpoint categories.

Courtesy translation only, please refer to the German original.