Linaclotid (1) – Constella®

• Clinical trials
  • This study is a multicentre, double-blind, parallel-group Phase II dose-finding trial with a 12-week treatment period, in which 496 patients diagnosed with RDS-O according to ROM-II criteria were enrolled.
  • The MCP-103-302 study is a multicentre, double-blind, parallel-group, placebo-controlled pivotal trial conducted in the USA in 2009 and 2010.
  • This double-blind, parallel-group, placebo-controlled registration study was conducted at several centres in the USA and Canada between July 2009 and July 2010.

Patients with moderate to severe irritable bowel syndrome with constipation (IBS-C)

• Based on these considerations, the information in the dossier, the results of the benefit assessment and the statements submitted, the G-BA finds no proof of additional benefit from linaclotide compared with the appropriate comparator therapy—a change in diet in accordance with medical advice and symptom-oriented treatment (constipation, bloating, cramps, pain).
• Side effects
  • With regard to side effects, diarrhoea is the most common adverse drug reaction.
  • According to the EPAR, this occurred in 160 (20 %) of the patients treated with linaclotide in the study population, compared with 24 (3 %) of those receiving placebo.
  • Of these, 91 patients in the linaclotide group and 6 patients in the placebo group suffered from moderate to severe diarrhoea.
  • In 50 % of the affected linaclotide patients, the diarrhoea persisted for more than 28 days, whilst around one third experienced episodes lasting less than seven days.
  • With regard to therapy discontinuations due to treatment-related side effects, both registration studies showed an increased number of discontinuations with linaclotide compared with placebo (LIN-MD-31: 7.9% vs. 2.5%; MCP-103-302: 10.2% vs. 2.5%).

Courtesy translation only, please refer to the German original.