Multiple dose study of LJN452 in patients with PBAD

• Research type

  Research Study

• Full title

  A double blind, randomized placebo controlled crossover multiple dose study of LJN452 to assess safety, tolerability and efficacy in patients with primary bile acid diarrhea (PBAD).

• IRAS ID

  190075

• Contact name

  Julian Walters

• Contact email

  julian.walters@imperial.ac.uk

• Sponsor organisation

  Novartis Pharma Services AG

• Eudract number

  2015-003192-30

• Duration of Study in the UK

  1 years, 7 months, 6 days

• Research summary

  Bile acid diarrhoea (BAD) is an under­recognised but common condition of chronic watery diarrhoea. BAD may be secondary to ileal disease affecting the reabsorption of bile acids (bile acid malabsorption) or can be of unknown cause (idiopathic) termed primary BAD (PBAD).

  In PBAD, blood levels of the hormone fibroblast growth factor 19 (FGF19) are reduced which produces impaired feedback inhibition of bile acid synthesis. This leads to excess faecal bile acids, which then produce diarrhoea by stimulating secretion in the colon. FGF19 is known to be synthesised in the ileum (small intestine) in response to activation of Farnesoid­X­receptors (FXRs) by agonists such as chenodeoxycholic acid (an abundant natural bile acid). LJN452 (investigational drug) is also a FXR agonist that is being developed by Novartis for the treatment of PBAD.

  The purpose of this study is to determine whether LJN452 improves the symptoms of bile acid diarrhea, is safe and tolerated (will be taken) in patients with primary bile acid diarrhea (PBAD).

  Patients with PBAD will enter this study which consists of 4 parts that will run in the following order. A screening/run in period (up to 28 days), treatment period 1 (14 days), a washout period (up to 28 days) followed by treatment period 2 (14 days). The duration for each patient entering the study will be a maximum of 13 weeks.

  Patients will be given either placebo capsules or LJN452 capsules to take daily for 14 days in treatment period 1. Patients who receive placebo in treatment period 1 will receive LJN452 in treatment period 2 (and vice-versa). Patients with PBAD will take part in the study at hospital sites the UK.

  The study results will be used to make decisions on future clinical development of LJN452.

• REC name

  London - Brent Research Ethics Committee

• REC reference

  16/LO/0351

• Date of REC Opinion

  11 Mar 2016

• REC opinion

  Favourable Opinion