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

Primary Biliary Cirrhosis Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02963077
• Other study ID #: A4250-001
• Secondary ID: 2013-001175-21
• Status: Completed
• Phase: Phase 1
• Start date: July 2013
• Est. completion date: May 2014

Study information

• Verified date: March 2024
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Alagille Syndrome
• Cholestasis
• Cholestasis, Intrahepatic
• Liver Cirrhosis, Biliary
• Liver Diseases
• Orphan Cholestatic Liver Diseases
• Primary Biliary Cirrhosis
• Progressive Familial Intrahepatic Cholestasis

Intervention

Drug:
• A4250

• CRC (A3384)

• Questran

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Albireo

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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.
Primary	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.
Primary	Geometric (geometric CV%) Mean for AUC(0-12) on Day 7 for plasma FGF19		AUC(0-12) on Day 7 (only for Part II)
Primary	Geometric (geometric CV%) Mean for AUC(0-12) on Day 7 for plasma C4		AUC(0-12) on Day 7 (only Part II)
Primary	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)
Primary	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
Primary	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