To Assess Safety, Tolerability and Efficacy of LJN452 in Patients With Primary Bile Acid Diarrhea.

Phase 2

Completed

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Placebo followed by LJN452	Placebo to LJN452	Randomized patients in this arm will receive single oral dose of placebo daily for 14 days. There will be a washout period between 7 to 28 days followed by single oral dose of LJN452 daily for 14 days.
LJN452 followed by placebo	LJN452	Randomized patients in this arm will receive single oral dose of LJN452 daily for 14 days. There will be a washout period between 7 to 28 days followed by single oral dose of placebo daily for 14 days.
LJN452 followed by placebo	Placebo to LJN452	Randomized patients in this arm will receive single oral dose of LJN452 daily for 14 days. There will be a washout period between 7 to 28 days followed by single oral dose of placebo daily for 14 days.
Placebo followed by LJN452	LJN452	Randomized patients in this arm will receive single oral dose of placebo daily for 14 days. There will be a washout period between 7 to 28 days followed by single oral dose of LJN452 daily for 14 days.

Primary Outcome Measures

Name	Time	Method
Number of Patients Reported With Adverse Events , Serious Adverse Events and Death.	up to Day 79	Number of patients reported with adverse events , serious adverse events and death.
Stool Frequency at Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 Combined	Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 combined	Stool frequency at Baseline, Week 1 (Period 1 \& Period 2), Week 2 (Period 1 \& Period 2), and Week 1 \& 2 combined
Stool Form at Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 Combined	Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 combined	Stool Form at Baseline, Week 1 (Period 1 \& Period 2), Week 2 (Period 1 \& Period 2), and Week 1 \& 2 combined Clinical Symptoms will be measured as change from baseline in stool types per Bristol Stool Scale. The Bristol Stool Scale is a medical aid designed to classify feces on a scale from 1 to 7 according to increasing wateriness.

Secondary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration-time Profile (AUCtau) of LJN452	Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2)	AUCtau- is the area under the plasma (or serum or blood) concentration-time curve from time zero to the end of the dosing interval tau \[mass x time / volume\]
Time to Reach Maximum Concentration After Drug Administration (Tmax)	Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2)	Tmax is the time to reach the maximum concentration after drug administration \[time\]
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	Baseline, Week 1 (Period 1 & 2), Week 2 (Period 1 & 2), Week 1 & 2 combined	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; Rescue Medication used was loperamide
(Cmax) of LJN452	Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2)	Cmax is the observed maximum plasma (or serum or blood) concentration following drug administration \[mass / volume\]