Clinical trial NCT02713243: To Assess Safety, Tolerability and Efficacy of LJN452 in Patients With Primary Bile Acid Diarrhea.
Official 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Bile Acid Diarrhea
Keywords: Primary bile acid diarrhea,
FXR agonist,
bile acid malabsorption.
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-03-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether LJN452 improves the symptoms of bile acid diarrhea and to assess its safety and tolerability profile in patients with primary bile acid diarrhea (pBAD) to guide decision-making regarding further clinical development in this indication.


Eligibility criteria: Key Inclusion Criteria:

* A history of diarrheal symptoms for at least 3 months prior to dosing - Average stool frequency of at least 2 per day when off therapy AND Average stool form of \>5 on Bristol Stool Chart.
* Previous laboratory or radiological confirmation of bile acid malabsorption with either fecal bile acid loss OR 7 day 75Selenium homocholic acid taurine (75SeHCAT) retention.
* Age ≥ 18 years.

Key Exclusion Criteria:

* Patients with other diagnoses leading to diarrhea, including colorectal neoplasia, ulcerative colitis, Crohn's disease, celiac disease, chronic pancreatitis, drug-induced diarrhea or active infection AND Patients who have not been investigated by standard clinical assessments to exclude these disorders.
* Treatment with bile acid sequestrants (colestyramine, colestipol, colesevelam) for 2 weeks before the first dose of LJN452. A washout of 14 days for these agents will be allowed before first dosing.
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
* A positive Hepatitis B surface antigen or Hepatitis C test result.
* History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.

Primary outcomes:
measure: Number of Patients Reported With Adverse Events , Serious Adverse Events and Death.
timeFrame: up to Day 79
measure: Stool Frequency at Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 Combined
timeFrame: Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 combined
measure: Stool Form at Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 Combined
timeFrame: Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 combined
Secondary outcomes:
measure: Area Under the Plasma Concentration-time Profile (AUCtau) of LJN452
timeFrame: Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2)
measure: (Cmax) of LJN452
timeFrame: Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2)
measure: Time to Reach Maximum Concentration After Drug Administration (Tmax)
timeFrame: Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2)
measure: Total Dose of Rescue Medication Used at Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 Combined
timeFrame: Baseline, Week 1 (Period 1 & 2), Week 2 (Period 1 & 2), Week 1 & 2 combined
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Harrow
country: United Kingdom
facility: Novartis Investigative Site
state: Middlesex
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Sheffield
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Study Director Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Camilleri M, Nord SL, Burton D, Oduyebo I, Zhang Y, Chen J, Im K, Bhad P, Badman MK, Sanders DS, Walters JRF. Randomised clinical trial: significant biochemical and colonic transit effects of the farnesoid X receptor agonist tropifexor in patients with primary bile acid diarrhoea. Aliment Pharmacol Ther. 2020 Sep;52(5):808-820. doi: 10.1111/apt.15967. Epub 2020 Jul 23.