Non-interventional study with Binosto 70 mg effervescent tablets once weekly investigating gastro-intestinal events and medication errors (Gastro-PASS)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  BINOSTO ONCE WEEKLY
• Medicinal product name, other:
  Binosto
• Study drug International non-proprietary name (INN) or common name:
  ALENDRONATE SODIUM TRIHYDRATE
• Anatomical Therapeutic Chemical (ATC) code:
  (M05BA04) alendronic acid

  alendronic acid

Population studied

• Short description of the study population:
  Inclusion criteria were patients newly prescribed ALN EFF and naïve to bisphosphonate therapy; women with osteoporosis; written informed consent; and the ability to comply with the requirements of the study. Patients with a history of upper GI symptoms were also included. Exclusion criteria were the presence of any contraindications to ALN EFF according to Summary of Product Characteristics (SmPC).
• Age groups:
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Estimated number of subjects:
  1.200

Study design details

• Study design:
  Prospective, observational, multicenter, multinational, single arm, postauthorization safety study (PASS)
• Main study objective:
  The primary objective of the study is to investigate known safety concerns associated with oral bisphosphonates, namely oesophageal toxicity, gastritis, gastric ulcers and duodenitis, as well as medication errors that may be relevant to alendronic acid 70 mg effervescent tablets (Binosto), a novel pharmaceutical formulation of alendronate.
• Data analysis plan:
  Analyses will be mainly descriptive for the overall study population and subgroups. Comparisons will be made at baseline between the Binosto cohort and the non-concurrent cohort. For the longitudinal phase, the cumulative incidence (proportion) of the primary and secondary endpoints will be calculated with 95% confidence intervals. A univariate analysis of differences between the Binosto cohort and the non-concurrent cohort will be conducted for the frequency and incidence of upper gastrointestinal adverse events, using chi-square tests and relative incidence rates with 95% confidence intervals. The proportion (and 95% confidence intervals) of subjects with medication errors will be calculated. Persistence and discontinuation will be analysed using Kaplan-Meier curves. The incidence rates and their 95% confidence intervals for solicited individual gastric AEs, at each of the three follow-up visits and overall at the end of the prospective study, will be calculated.
• Summary results:
  Patients (N = 1028) aged 67 ± 9 years (mean ± SD) received ALN EFF weekly. The cumulative incidence of upper GI AEs (oesophageal toxicity, gastritis, gastric ulcers, and duodenitis) related to ALN EFF (primary endpoint) was 9.6% (95% confidence interval [CI] 7.9–11.6%), the vast majority being of mild intensity. The most frequently occurring upper GI AEs related to ALN EFF were dyspepsia (2.7%), gastroesophageal reflux disease (2.4%), and nausea (2.2%). None of the relevant upper GI AEs listed in the primary endpoint and no serious AEs were reported. At least one medication error occurred in 29.9% (95% CI 27.1–32.8%) of patients. However, the majority of medication errors were associated with administration instructions applicable to any oral bisphosphonate and only seven medication errors were associated with the ALN EFF formulation. ALN EFF was discontinued in 209 of 1028 (20.3%) patients. The most frequent reasons for discontinuation were AEs related to ALN EFF (46.9%) and patients' decision (42.6%). Compliance with ALN EFF was high, reflected by a mean Morisky Green score of 92.8 ± 18.6. PMW with osteoporosis treated with ALN EFF in a real world setting experienced few upper GI AEs. In addition, they had a low discontinuation and high compliance compared with other formulations, suggesting that ALN EFF may increase patient satisfaction and therefore long term adherence and efficacy.