Back to results

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

Primary Purpose

Primary Bile Acid Diarrhea

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

LJN452

Placebo to LJN452

About this trial

This is an interventional treatment trial for Primary Bile Acid Diarrhea focused on measuring Primary bile acid diarrhea,, FXR agonist,, bile acid malabsorption.

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

LJN452 followed by placebo

Placebo followed by LJN452

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

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

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

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

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

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]

(Cmax) of LJN452

Cmax is the observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume]

Time to Reach Maximum Concentration After Drug Administration (Tmax)

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

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

Full Information

NCT ID

NCT02713243

First Posted

March 15, 2016

Last Updated

December 9, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02713243

Brief Title

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

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

January 16, 2016 (Actual)

Primary Completion Date

January 25, 2018 (Actual)

Study Completion Date

January 25, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Bile Acid Diarrhea

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LJN452 followed by placebo

Arm Type

Experimental

Arm Description

Arm Title

Placebo followed by LJN452

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

LJN452

Intervention Description

Capsules containing LJN452

Intervention Type

Drug

Intervention Name(s)

Placebo to LJN452

Intervention Description

Capsules containing placebo to LJN452

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

up to Day 79

Title

Stool Frequency at Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 Combined

Description

Stool frequency at Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 combined

Time Frame

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

Title

Stool Form at Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 Combined

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

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 Frame

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

Title

(Cmax) of LJN452

Description

Cmax is the observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume]

Time Frame

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

Title

Time to Reach Maximum Concentration After Drug Administration (Tmax)

Description

Tmax is the time to reach the maximum concentration after drug administration [time]

Time Frame

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

Title

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

Description

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

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Study Director Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

Novartis Investigative Site

City

Harrow

State/Province

Middlesex

ZIP/Postal Code

HA1 3UJ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

London

ZIP/Postal Code

W2 1PG

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Sheffield

ZIP/Postal Code

S10 2JF

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

32702169

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.

Results Reference

derived

Links:

URL

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=372

Description

A Plain Language Trial Summary is available on novartisclinicatrials.com

Learn more about this trial

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

We'll reach out to this number within 24 hrs