Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2015-003192-30 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LJN452 | Drug | Capsules containing LJN452 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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] | Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2) |
| (Cmax) of LJN452 |
Not provided
Key Inclusion Criteria:
Key Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Study Director Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Rochester | Minnesota | 55905 | United States | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32702169 | Derived | 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. |
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novartisclinicatrials.com | View source |
Not provided
Not provided
In total, 20 patients were enrolled in this study and received at least one dose of LJN452 or matching placebo for 14 days in Period 1. There will be a washout period between 7 to 28 days followed by Period 2 drug if patient on LJN452 or Placebo in Period 1 they will take Placebo or LJN452 respectively in Period 2 for 14 days
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | LJN452 Followed by Placebo | 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. |
| FG001 | Placebo Followed by 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | LJN452 Followed by Placebo | 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. |
| BG001 | Placebo Followed by LJN452 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients Reported With Adverse Events , Serious Adverse Events and Death. | Number of patients reported with adverse events , serious adverse events and death. | 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. | Posted | Number | count of participants | up to Day 79 |
|
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).
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LJN452 ALL Patients | All Patients on LJN452 in both Period 1 and Period 2 | 0 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 8627788300 | novartis.email@novartis.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 14, 2016 | Apr 10, 2019 | SAP_001.pdf |
| Prot | Yes | No | No | Study Protocol | Aug 15, 2016 | Aug 19, 2019 | Prot_002.pdf |
| ID | Term |
|---|---|
| C000630573 | tropifexor |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo to LJN452 | Drug | Capsules containing placebo to LJN452 |
|
Cmax is the observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume] |
| 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] | 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 | Baseline, Week 1 (Period 1 & 2), Week 2 (Period 1 & 2), Week 1 & 2 combined |
| Harrow |
| Middlesex |
| HA1 3UJ |
| United Kingdom |
| Novartis Investigative Site | London | W2 1PG | United Kingdom |
| Novartis Investigative Site | Sheffield | S10 2JF | United Kingdom |
| Protocol deviation |
|
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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
All Patients on Placebo in both Period 1 and Period 2
|
|
| Primary | 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 | PD analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. | Posted | Mean | Standard Deviation | Stools per week | Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 combined |
|
|
|
|
| Secondary | 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] | PK analysis set: Patients with at least one valid PK concentration measurement and no major protocol deviations affecting PK No statistical Analysis | Posted | Mean | Standard Deviation | hr*ng/mL | Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2) |
|
|
|
| Secondary | (Cmax) of LJN452 | Cmax is the observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume] | PK analysis set: Patients with at least one valid PK concentration measurement and no major protocol deviations affecting PK - No statistical Analysis | Posted | Mean | Standard Deviation | ng/mL | Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2) |
|
|
|
| Secondary | Time to Reach Maximum Concentration After Drug Administration (Tmax) | Tmax is the time to reach the maximum concentration after drug administration [time] | PK analysis set: Patients with at least one valid PK concentration measurement and no major protocol deviations affecting PK; No statistical Analysis | Posted | Median | Full Range | hr | Day 1 (Period 1 & 2) and Day 12 (Period 1 & 2) |
|
|
|
| Secondary | 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 | 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. | Posted | Mean | Standard Deviation | mg | Baseline, Week 1 (Period 1 & 2), Week 2 (Period 1 & 2), Week 1 & 2 combined |
|
|
|
| Primary | 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. | PD analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 1 (Period 1 & Period 2), Week 2 (Period 1 & Period 2), and Week 1 & 2 combined |
|
|
|
|
| 17 |
| 0 |
| 17 |
| 9 |
| 17 |
| EG001 | Placebo ALL Patients | All Patients on Placebo in both Period 1 and Period 2 | 0 | 19 | 0 | 19 | 14 | 19 |
| Abdominal distension | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Anal incontinence | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Bile acid malabsorption | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Frequent bowel movements | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (20.1) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (20.1) | Systematic Assessment |
|
| Biliary dyspepsia | Hepatobiliary disorders | MedDRA (20.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA (20.1) | Systematic Assessment |
|
| Limb injury | Injury, poisoning and procedural complications | MedDRA (20.1) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (20.1) | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
| Week 1 (Period 1 & 2) |
|
|
| Week 2 (Period 1 & 2) |
|
|
| Week 1 & 2(Period 1 & 2) |
|
|
| 0.401 |
| Mean Difference (Net) |
| 1.31 |
| 2-Sided |
| 95 |
| -1.77 |
| 4.38 |
| Superiority |
| Week 1&2 (Period 1 & 2) | Mixed Models Analysis | 0.019 | Mean Difference (Net) | 2.67 | 2-Sided | 95 | 0.46 | 4.89 | Superiority |
|
|
|
| Week 1 (Period 1 & 2) |
|
|
| Week 2 (Period 1 & 2) |
|
|
| Week 1 & 2(Period 1 & 2) |
|
|
| Week 1 (Period 1 & 2) |
|
|
| Week 2 (Period 1 & 2) |
|
|
| Week 1 & 2(Period 1 & 2) |
|
|
| 0.640 |
| Mean Difference (Net) |
| -0.09 |
| 2-Sided |
| 95 |
| -0.49 |
| 0.30 |
| Superiority |
| Week 1&2 (Period 1 & 2) | Mixed Models Analysis | 0.916 | Mean Difference (Net) | 0.02 | 2-Sided | 95 | -0.27 | 0.30 | Superiority |