A Safety and Pharmakokinetic Study of A4250 Alone or in Combination With A3384

• Register: ClinicalTrials.gov
• Last refreshed on: 18 March 2024
• Main ID: NCT02963077
• Date of registration: 01/11/2016
• Prospective Registration: No
• Primary sponsor: Albireo
• Public title: A Safety and Pharmakokinetic Study of A4250 Alone or in Combination With A3384
• Scientific title: A Phase I, Double-Blind Single and Multiple Ascending Dose Study to Assess Safety and Pharmacokinetics of A4250 as Monotherapy, and in Combination With Colonic Release Cholestyramine (A3384) or Commercially Available Cholestyramine (Questran™) in Healthy Subjects
• Date of first enrolment: July 2013
• Target sample size: 94
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02963077
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 1

Contacts

• Name: Ipsen Medical Director
• Affiliation: Ipsen

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Healthy males or non-pregnant, non-lactating healthy females

2. BMI of 18 to 32 kg/m2 or, if outside the range, considered not clinically significant
by the investigator

3. Willing and able to communicate and participate in the whole study

4. Provided written informed consent

5. Agreed to use an adequate method of contraception

Exclusion Criteria:

1. Had participated in a clinical research study within the previous 3 months

2. Were study site employees, or immediate family members of a study site or sponsor
employee

3. Had previously been enrolled in this study

4. History of any drug or alcohol abuse in the past 2 years

5. Regular alcohol consumption, in males >21 units per week and females >14 units per
week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)

6. Current smokers and those who had smoked within the last 12 months. A breath carbon
monoxide (CO) reading of greater than 10 ppm at screening

7. Females of childbearing potential who were pregnant or lactating (female subjects must
have had a negative urine pregnancy test at admission)

8. Did not have suitable veins for multiple venepunctures/cannulation as assessed by the
investigator at screening

9. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by
the investigator

10. Positive drugs of abuse test result

11. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or
human immunodeficiency virus (HIV) results

12. History of cardiovascular, renal, hepatic, chronic respiratory or GI disease as judged
by the investigator

13. Serious adverse reaction or serious hypersensitivity to any drug or the formulation
excipients eg lactose or contraindications to cholestyramine/Questran

14. Presence or history of clinically significant allergy requiring treatment as per the
judgement of the investigator Hayfever was allowed unless it was active

15. Donation or loss of greater than 400 mL of blood within the previous 3 months

16. Were taking, or had taken, any prescribed or over-the-counter drug (other than up to 4
g per day paracetamol, hormone replacement therapy [HRT] and hormonal contraception)
or herbal remedies in the 14 days before IMP administration unless they were not
considered to have interfered with the objectives of the study, as agreed by the PI
and sponsor's medical monitor on a case by case basis

17. Failed to satisfy the investigator of fitness to participate for any other reason



Age minimum: 18 Years
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

Alagille Syndrome

Orphan Cholestatic Liver Diseases

Primary Biliary Cirrhosis

Progressive Familial Intrahepatic Cholestasis

Intervention(s)

Drug: A4250

Drug: Placebo

Drug: Questran

Drug: CRC (A3384)

Primary Outcome(s)

Mean (± SD) Plasma Pharmacokinetic Concentrations of A4250 Following A Single Oral 10 mg A4250 Dose - Tmax [Time Frame: 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 C4 from Day 1 Pre-Dose to 24 h Post-Dose [Time Frame: 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) Plasma Pharmacokinetic Concentrations of A4250 Following a Single Oral 10 mg A4250 Dose - Cmax [Time Frame: 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]

Geometric (geometric CV%) Mean for AUC(0-12) on Day 7 for plasma FGF19 [Time Frame: AUC(0-12) on Day 7 (only for Part II)]

Mean (± SD) Plasma Pharmacokinetic Concentrations of A4250 Following a Single Oral 10 mg A4250 Dose - AUC 0-t [Time Frame: 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) Changes in Faecel Total Bile Acids from Day 1 Pre-Dose on Day 7 at 24 h Post-dose [Time Frame: Change from Day 1 Pre-dose to Day 7 at 24 hours Post-dose]

Mean (SD) Change in C4 from Day 1 Pre-Dose to 4 h Post-Dose [Time Frame: 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) Changes in Total Bile Acids for A4250 24 h compared to pre-dose [Time Frame: Samples were taken pre-dose, and post-dose at 4 hours and 24 hours.]

Mean (SD) Change in Faecal Total Bile Acids Excreted (ng) from Day 1 Pre-Dose on Day 7 Post-Dose [Time Frame: Change from Day 1 Pre-dose to Day 7 at 24 hours Post-dose]

Mean (SD) Changes in Total Bile Acids for A4250 4 h compared to pre-dose [Time Frame: Samples were taken pre-dose and post-dose at 4 hours and 24 hours.]

Mean (SD) Change in FGF19 from Day 1 Pre-Dose to 24 h Post-Dose [Time Frame: 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).]

Geometric (geometric CV%) Mean for AUC(0-12) on Day 7 for plasma C4 [Time Frame: 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 [Time Frame: AUC(0-12) on Day 7 (only Part II)]

Mean (SD) Change in FGF19 from Day 1 Pre-Dose to 4 h Post-Dose [Time Frame: 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).]

Secondary ID(s)

2013-001175-21

A4250-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors