E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
primary bile acid diarrhea |
|
E.1.1.1 | Medical condition in easily understood language |
primary bile acid diarrhea |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10032786 |
E.1.2 | Term | Other specified intestinal malabsorption |
E.1.2 | System Organ Class | 100000004856 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•Safety and tolerability
•clinical symptoms |
|
E.2.2 | Secondary objectives of the trial |
•the pharmacokinetics of LJN452
•effect of LJN452 on use of rescue |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• A history of diarrheal symptoms for at least 3 months prior to dosing - Average stool frequency of at least 3 per day when off therapy AND Average stool form of >5 on Bristol Stool Chart.
•Previous laboratory or radiological confirmation of bile acid
malabsorption within the last 5 years with either fecal bile acid loss of ≥2,000 μmol per 48 hours OR 7 day 75Selenium
homocholic acid taurine (75SeHCAT) retention.
• Age ≥ 18 years |
|
E.4 | Principal 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.
•History of extrahepatic biliary obstructive disease or complete biliary obstruction.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception.
• 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Safety endpoints include type and frequency of adverse events, serious adverse events, and laboratory, vital signs, physical, and ECG
abnormalities.
•Change from baseline in stool frequency and stool form per Bristol Stool Chart. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
•across all visits
•predose, end of treatment period 1 and period 2 |
|
E.5.2 | Secondary end point(s) |
•Tmax, Cmax and AUCtau of LJN452.
•Use and type of rescue medications |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Day 1 and Day 12 in each treatment period
•all visits |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Germany |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |