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Completed

NCT Number: NCT02963077

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

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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Key information

Conditions

Orphan Cholestatic Liver Diseases Abnormalities, Multiple Alagille Syndrome Bile Duct Diseases Biliary Tract Diseases Cardiovascular Abnormalities Cardiovascular Diseases Cholestasis Cholestasis, Intrahepatic Cholestasis, progressive familial intrahepatic 1 Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Fibrosis Genetic Diseases, Inborn Heart Defects, Congenital Liver Cirrhosis Liver Cirrhosis, Biliary Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Primary Biliary Cirrhosis Progressive Familial Intrahepatic Cholestasis

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy males or non-pregnant, non-lactating healthy females
  • BMI of 18 to 32 kg/m2 or, if outside the range, considered not clinically significant by the investigator
  • Willing and able to communicate and participate in the whole study
  • Provided written informed consent
  • Agreed to use an adequate method of contraception

Exclusion criteria

  • Had participated in a clinical research study within the previous 3 months
  • Were study site employees, or immediate family members of a study site or sponsor employee
  • Had previously been enrolled in this study
  • History of any drug or alcohol abuse in the past 2 years
  • 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)
  • 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
  • Females of childbearing potential who were pregnant or lactating (female subjects must have had a negative urine pregnancy test at admission)
  • Did not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
  • Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator
  • Positive drugs of abuse test result
  • Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
  • History of cardiovascular, renal, hepatic, chronic respiratory or GI disease as judged by the investigator
  • Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients eg lactose or contraindications to cholestyramine/Questran
  • Presence or history of clinically significant allergy requiring treatment as per the judgement of the investigator Hayfever was allowed unless it was active
  • Donation or loss of greater than 400 mL of blood within the previous 3 months
  • 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
  • Failed to satisfy the investigator of fitness to participate for any other reason

Treatment and study plan

A4250

Drug

CRC (A3384)

Drug

Questran

Drug

Placebo

Drug

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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).

  5. 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).

  6. 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).

  7. 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).

  8. 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.

  9. 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.

  10. 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)

  11. 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)

  12. 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)

  13. 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

  14. 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

Sponsors and collaborators

Lead sponsor

Albireo

Industry

Registry information

Official study 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

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Nov 15, 2016
Registry last updated
Mar 7, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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