NCT02713243

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jan 2016

Geographic Reach
2 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 16, 2016

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

March 15, 2016

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 18, 2016

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 25, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 25, 2018

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

May 1, 2019

Completed
Last Updated

January 5, 2021

Status Verified

August 1, 2019

Enrollment Period

2 years

First QC Date

March 15, 2016

Results QC Date

January 25, 2019

Last Update Submit

December 9, 2020

Conditions

Primary Bile Acid Diarrhea

Keywords

Primary bile acid diarrhea,FXR agonist,bile acid malabsorption.

Outcome Measures

Primary Outcomes (3)

  • Number of Patients Reported With Adverse Events , Serious Adverse Events and Death.

    Number of patients reported with adverse events , serious adverse events and death.

    up to Day 79

  • Stool Frequency at 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

    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

    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.

    Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 combined

Secondary Outcomes (4)

  • Area Under the Plasma Concentration-time Profile (AUCtau) of LJN452

    Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2)

  • (Cmax) of LJN452

    Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2)

  • Time to Reach Maximum Concentration After Drug Administration (Tmax)

    Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2)

  • 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

Study Arms (2)

LJN452 followed by placebo

EXPERIMENTAL

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.

Drug: LJN452Drug: Placebo to LJN452

Placebo followed by LJN452

EXPERIMENTAL

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.

Drug: LJN452Drug: Placebo to LJN452

Interventions

LJN452DRUG

Capsules containing LJN452

LJN452 followed by placeboPlacebo followed by LJN452
Placebo to LJN452DRUG

Capsules containing placebo to LJN452

LJN452 followed by placeboPlacebo followed by LJN452

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Novartis Investigative Site

Rochester, Minnesota, 55905, United States

Location

Novartis Investigative Site

Harrow, Middlesex, HA1 3UJ, United Kingdom

Location

Novartis Investigative Site

London, W2 1PG, United Kingdom

Location

Novartis Investigative Site

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 32702169DERIVED

Related Links

MeSH Terms

Interventions

tropifexor

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals
novartis.email@novartis.com
8627788300

Study Officials

  • Study Director Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 15, 2016

First Posted

March 18, 2016

Study Start

January 16, 2016

Primary Completion

January 25, 2018

Study Completion

January 25, 2018

Last Updated

January 5, 2021

Results First Posted

May 1, 2019

Record last verified: 2019-08

Locations

US(1)GB(3)