Primary Bile Acid DiarrheaPhase 2NCT02713243

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

A Phase 2 study testing LJN452 in people with Primary Bile Acid Diarrhea, run by Novartis Pharmaceuticals at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Primary Bile Acid Diarrhea
What is being tested?: LJN452
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 20 participants
Where: 4 sitesin 2 countries
Study dates: 16 Jan 2016to 25 Jan 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

4 sites in 2 countries.

Country

City, postcode or hospital

4 sites in 2 countries

United Kingdom3 sites

Novartis Investigative Site
Harrow, Middlesex, HA1 3UJ
Novartis Investigative Site
London, W2 1PG
Novartis Investigative Site
Sheffield, S10 2JF

Other trials in United Kingdom

United States1 site

Novartis Investigative Site
Rochester, Minnesota, 55905

Other trials in United States

About this study

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).

Conditions: Primary Bile Acid Diarrhea
Being tested: LJN452, Placebo to LJN452
Keywords: Primary bile acid diarrhea,, FXR agonist,, bile acid malabsorption.

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LJN452Drug
Capsules containing LJN452
Placebo to LJN452Drug
Capsules containing placebo to LJN452

Study groups in NCT02713243
Study group	Role	What they receive
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. Receives: Drug: LJN452; Drug: 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. Receives: Drug: LJN452; Drug: Placebo to LJN452

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Patients Reported With Adverse Events , Serious Adverse Events and Death.
Number of patients reported with adverse events , serious adverse events and death.
Measured: 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
Measured: 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.
Measured: 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
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]
Measured: Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2)
(Cmax) of LJN452
Cmax is the observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume]
Measured: Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2)
Time to Reach Maximum Concentration After Drug Administration (Tmax)
Tmax is the time to reach the maximum concentration after drug administration [time]
Measured: 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
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
Measured: Baseline, Week 1 (Period 1 & 2), Week 2 (Period 1 & 2), Week 1 & 2 combined

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Jan 201625 Jan 2018

First posted18 Mar 2016 (estimated)
Study start16 Jan 2016
Primary completion25 Jan 2018
Study completion25 Jan 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Primary Bile Acid DiarrheaStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02713243
Sponsor's protocol ID: CLJN452X2202
Other IDs: 2015-003192-30, 2015
Status last verified: Aug 2019
First submitted: 15 Mar 2016
Last updated: 5 Jan 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 32702169

Study at a glance

From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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).
ClinicalTrials.gov ID: NCT02713243
Acronym / sponsor ID: CLJN452X2202
Conditions: Primary Bile Acid Diarrhea
Keywords: Primary bile acid diarrhea,, FXR agonist,, bile acid malabsorption.
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 16 Jan 2016 (actual)
Primary completion: 25 Jan 2018 (actual)
Study completion: 25 Jan 2018 (actual)
First posted: 18 Mar 2016 (estimated)
Results: Posted 1 May 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
LJN452 followed by placebo	Experimental	Drug: LJN452, Drug: Placebo to LJN452Randomized 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	Experimental	Drug: LJN452, Drug: Placebo to LJN452Randomized 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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 (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LJN452Capsules containing LJN452	Drug	LJN452 followed by placebo, Placebo followed by LJN452
Placebo to LJN452Capsules containing placebo to LJN452	Drug	LJN452 followed by placebo, Placebo followed by LJN452

Primary outcome

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

4 secondary outcomes

Area Under the Plasma Concentration-time Profile (AUCtau) of LJN452
Time frame: Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2)
(Cmax) of LJN452
Time frame: Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2)
Time to Reach Maximum Concentration After Drug Administration (Tmax)
Time frame: 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
Time frame: Baseline, Week 1 (Period 1 & 2), Week 2 (Period 1 & 2), Week 1 & 2 combined

Results and safety

Results posted to the registry on 1 May 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
LJN452 Followed by Placebo	10	9
Placebo Followed by LJN452	10	8

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

Time frame: up to Day 79. Number. Unit: count of participants

Measure	LJN452 ALL Patients n = 17	Placebo ALL Patients n = 19
AEs, Patients with AEs	9	14
Study drug-related AEs	0	4
Serious AEs	0	0
Death	0	0

Population analysed: Safety analysis set consists of 20 patients(10 pts per treatment period),17 \&19 patients received at least 1 LJN \& 1 Placebo dose, respectively, therefore 17 pts in the LJN452 \&19 in the Placebo treatment periods were analyzed. Adverse events were summarized using descriptive statistics only with no formal statistical analysis performed.

Primary outcome: 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. Mean (Standard Deviation). Unit: Stools per week

Measure	LJN452 ALL Patients n = 20	Placebo ALL Patients n = 20
Baseline	18.0 (9.39)	15.9 (6.92)
Week 1 (Period 1 & 2)	20.0 (11.62)	16.2 (7.19)
Week 2 (Period 1 & 2)	18.8 (9.68)	17.5 (10.88)
Week 1 & 2(Period 1 & 2)	19.4 (10.56)	16.8 (9.11)

LJN452 ALL Patients vs Placebo ALL Patients: Mean Difference (Net): 4.04 (95% CI 0.98 to 7.11), p = 0.01, Mixed Models Analysis
LJN452 ALL Patients vs Placebo ALL Patients: Mean Difference (Net): 1.31 (95% CI -1.77 to 4.38), p = 0.401, Mixed Models Analysis
LJN452 ALL Patients vs Placebo ALL Patients: Mean Difference (Net): 2.67 (95% CI 0.46 to 4.89), p = 0.019, Mixed Models Analysis

Population analysed: PD analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data.

Primary outcome: Stool Form 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. Mean (Standard Deviation). Unit: score on a scale

Measure	LJN452 ALL Patients n = 20	Placebo ALL Patients n = 20
Baseline	5.5 (0.87)	5.1 (0.94)
Week 1 (Period 1 & 2)	5.3 (0.78)	5.3 (0.79)
Week 2 (Period 1 & 2)	4.9 (0.82)	5.1 (1.01)
Week 1 & 2(Period 1 & 2)	5.1 (0.81)	5.2 (0.90)

LJN452 ALL Patients vs Placebo ALL Patients: Mean Difference (Net): 0.12 (95% CI -0.27 to 0.52), p = 0.533, Mixed Models Analysis
LJN452 ALL Patients vs Placebo ALL Patients: Mean Difference (Net): -0.09 (95% CI -0.49 to 0.30), p = 0.640, Mixed Models Analysis
LJN452 ALL Patients vs Placebo ALL Patients: Mean Difference (Net): 0.02 (95% CI -0.27 to 0.30), p = 0.916, Mixed Models Analysis

Population analysed: PD analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events are monitored from date of First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) Day 79. All other adverse events are monitored from First Patient First Treatment until Last Patient Last Visit (Day 79).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
LJN452 ALL Patients	0 of 17 (0%)	9 of 17 (52.9%)	0 of 17
Placebo ALL Patients	0 of 19 (0%)	14 of 19 (73.7%)	0 of 19

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32702169Camilleri 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.
A Plain Language Trial Summary is available on novartisclinicatrials.comLink provided by the sponsor.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Study Director Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

4 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LJN452 in people with Primary Bile Acid Diarrhea, run by Novartis Pharmaceuticals at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United Kingdom, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients Reported With Adverse Events , Serious Adverse Events and Death. (time frame: up to Day 79). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02713243, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2021.