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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-001175-21 | EudraCT Number |
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The primary objectives of the study are to evaluate the safety, tolerability and pharmacokinetics of A4250 after single or multiple oral doses in healthy subjects. In addition, will evaluate A4250 in combination with cholestyramine.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 SAD - 0.1 mg A4250 | Experimental | Dose: 0.1 mg of A4250. Sentinel dosing was used (2 sub-cohorts dosed a minimum of 24 h apart). |
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| Cohort 2 SAD - 0.3 mg A4250 | Experimental | Dose: 0.3 mg of A4250. |
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| Cohort 3 SAD - 1 mg A4250 | Experimental | Dose: 1 mg A4250. |
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| Cohort 4 SAD - 3 mg A4250 | Experimental | Dose: 3 mg A4250. |
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| Cohort 5 SAD - 10 mg A4250 | Experimental | Dose: 10 mg A4250. |
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| Cohort 1 SAD placebo | Placebo Comparator | Dose: 0.1 mg of A4250 matching placebo. Sentinel dosing was used (2 sub-cohorts dosed a minimum of 24 h apart). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| A4250 | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean (± SD) Plasma Pharmacokinetic Concentrations of A4250 Following A Single Oral 10 mg A4250 Dose - Tmax | Pharmacokinetic blood samples were taken pre-dose, and post-dose at: 0.5 hour, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours | |
| Mean (± SD) Plasma Pharmacokinetic Concentrations of A4250 Following a Single Oral 10 mg A4250 Dose - Cmax | Pharmacokinetic blood samples were taken pre-dose, and post-dose at: 0.5 hour, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours | |
| Mean (± SD) Plasma Pharmacokinetic Concentrations of A4250 Following a Single Oral 10 mg A4250 Dose - AUC 0-t | Pharmacokinetic blood samples were taken pre-dose, and post-dose at: 0.5 hour, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours | |
| Mean (SD) Change in FGF19 from Day 1 Pre-Dose to 4 h Post-Dose | Pharmacodynamic blood samples were taken pre-dose and at 4 hours and 24 hours post-dosing, and at follow-up (5-7 days after final dose). | |
| Mean (SD) Change in FGF19 from Day 1 Pre-Dose to 24 h Post-Dose | Pharmacodynamic blood samples were taken pre-dose and at 4 hours and 24 hours post-dosing, and at follow-up (5-7 days after final dose). | |
| Mean (SD) Change in C4 from Day 1 Pre-Dose to 4 h Post-Dose | Pharmacodynamic blood samples were taken pre-dose and at 4 hours and 24 hours post-dosing, and at follow-up (5-7 days after final dose). | |
| Mean (SD) Change in C4 from Day 1 Pre-Dose to 24 h Post-Dose | Pharmacodynamic blood samples were taken pre-dose and at 4 hours and 24 hours post-dosing, and at follow-up (5-7 days after final dose). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ipsen Medical Director | Ipsen | Study Director |
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| ID | Term |
|---|---|
| D008105 | Liver Cirrhosis, Biliary |
| C535933 | Cholestasis, progressive familial intrahepatic 1 |
| D016738 | Alagille Syndrome |
| ID | Term |
|---|---|
| D002780 | Cholestasis, Intrahepatic |
| D002779 | Cholestasis |
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
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| ID | Term |
|---|---|
| D002792 | Cholestyramine Resin |
| ID | Term |
|---|---|
| D011137 | Polystyrenes |
| D010969 | Plastics |
| D011108 | Polymers |
| D046911 | Macromolecular Substances |
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| Cohort 2 SAD placebo | Placebo Comparator | Dose: 0.3 mg A4250 matching placebo. |
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| Cohort 3 SAD placebo | Placebo Comparator | Dose: 1 mg A4250 matching placebo. |
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| Cohort 4 SAD placebo | Placebo Comparator | Dose: 3 mg A4250 matching placebo. |
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| Cohort 5 SAD placebo | Placebo Comparator | Dose: 10 mg A4250 matching placebo. |
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| Cohort 1 MAD - 1 mg A4250 qd | Experimental | Dose: 1 mg A4250 qd for 7 days. |
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| Cohort 1 MAD placebo | Placebo Comparator | Dose: 1 mg A4250 matching placebo qd for 7 days. |
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| Cohort 2 MAD - 3 mg A4250 | Experimental | Dose: 3 mg A4250 qd for 7 days |
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| Cohort 2 MAD placebo | Placebo Comparator | Dose: 3 mg A4250 matching placebo qd for 7 days. |
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| Cohort 3 MAD - 1.5 mg A4250 b.i.d for 7 days. | Experimental | Dose: 1.5 mg A4250 b.i.d. for 7 days. |
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| Cohort 3 MAD placebo | Placebo Comparator | Dose: 1.5 A4250 matching placebo b.i.d for 7 days. |
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| Cohort 4 MAD - 3 mg A4250 qd + 1 mg Questran b.i.d | Experimental | Dose: 3 mg A4250 qd + 1 mg Questran b.i.d for 7 days. |
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| Cohort 4 MAD A4250 placebo + 1 mg Questran b.i.d | Active Comparator | Dose: 3 mg A4250 matching placebo + 1 mg Questran b.i.d for 7 days. |
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| Cohort 5 MAD - 3 mg A4250 qd + 1 g CRC b.i.d | Experimental | Dose: 3 mg A4250 qd + 1 g CRC b.i.d for 7 days. |
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| Cohort 5 MAD A4250 placebo + CRC placebo | Placebo Comparator | Dose: 3 mg A4250 matching placebo qd + 1 g CRC placebo b.i.d for 7 days |
|
| Cohort 6 MAD - 1 g CRC | Active Comparator | Dose: 1 g CRC b.i.d |
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| Cohort 6 MAD CRC placebo | Placebo Comparator | Dose: 1 g CRC matching placebo b.i.d. |
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| Cohort 7 MAD - 3 mg A4250 qd + 1 g CRC b.i.d | Experimental | Dose: 3 mg A4250 qd + 1 g CRC b.i.d |
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| Cohort 7 MAD A4250 placebo + CRC placebo | Placebo Comparator | Dose: 3 mg A4250 matching placebo qd + 1 g CRC matching placebo b.i.d. |
|
| CRC (A3384) | Drug |
|
| Questran | Drug |
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| Placebo | Drug |
|
| Mean (SD) Changes in Total Bile Acids for A4250 4 h compared to pre-dose | Samples were taken pre-dose and post-dose at 4 hours and 24 hours. |
| Mean (SD) Changes in Total Bile Acids for A4250 24 h compared to pre-dose | Samples were taken pre-dose, and post-dose at 4 hours and 24 hours. |
| Geometric (geometric CV%) Mean for AUC(0-12) on Day 7 for plasma FGF19 | AUC(0-12) on Day 7 (only for Part II) |
| Geometric (geometric CV%) Mean for AUC(0-12) on Day 7 for plasma C4 | AUC(0-12) on Day 7 (only Part II) |
| Geometric (geometric CV%) Mean for AUC(0-12) on Day 7 for plasma Total Bile Acids | AUC(0-12) on Day 7 (only Part II) |
| Mean (SD) Changes in Faecel Total Bile Acids from Day 1 Pre-Dose on Day 7 at 24 h Post-dose | Change from Day 1 Pre-dose to Day 7 at 24 hours Post-dose |
| Mean (SD) Change in Faecal Total Bile Acids Excreted (ng) from Day 1 Pre-Dose on Day 7 Post-Dose | Change from Day 1 Pre-dose to Day 7 at 24 hours Post-dose |
| D004066 |
| Digestive System Diseases |
| D008107 | Liver Diseases |
| D008103 | Liver Cirrhosis |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D001697 |
| Biomedical and Dental Materials |
| D008420 | Manufactured Materials |
| D013676 | Technology, Industry, and Agriculture |