Orphan Cholestatic Liver DiseasesPhase 1NCT02963077

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

A Phase 1 study testing A4250, CRC (A3384) and Questran in people with Orphan Cholestatic Liver Diseases and Primary Biliary Cirrhosis, run by Albireo.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

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. Read more about this study

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Orphan Cholestatic Liver Diseases, Primary Biliary Cirrhosis, Progressive Familial Intrahepatic Cholestasis
What is being tested?: A4250, CRC (A3384) and Questran
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 94 participants
Where: No sites listed yet
Study dates: Jul 2013to May 2014
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Show all 17Show fewer

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

About this study

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

Conditions: Orphan Cholestatic Liver Diseases, Primary Biliary Cirrhosis, Progressive Familial Intrahepatic Cholestasis, Alagille Syndrome
Being tested: A4250, CRC (A3384), Questran, Placebo
Medical subject headings: Liver Cirrhosis, Biliary, Cholestasis, progressive familial intrahepatic 1, Alagille Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

A4250Drug
CRC (A3384)Drug
QuestranDrug
PlaceboDrug

Study groups in NCT02963077
Study group	Role	What they receive
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). Receives: Drug: A4250
Cohort 2 SAD - 0.3 mg A4250	Experimental	Dose: 0.3 mg of A4250. Receives: Drug: A4250
Cohort 3 SAD - 1 mg A4250	Experimental	Dose: 1 mg A4250. Receives: Drug: A4250
Cohort 4 SAD - 3 mg A4250	Experimental	Dose: 3 mg A4250. Receives: Drug: A4250
Cohort 5 SAD - 10 mg A4250	Experimental	Dose: 10 mg A4250. Receives: Drug: A4250
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). Receives: Drug: Placebo
Cohort 2 SAD placebo	Placebo comparator	Dose: 0.3 mg A4250 matching placebo. Receives: Drug: Placebo
Cohort 3 SAD placebo	Placebo comparator	Dose: 1 mg A4250 matching placebo. Receives: Drug: Placebo
Cohort 4 SAD placebo	Placebo comparator	Dose: 3 mg A4250 matching placebo. Receives: Drug: Placebo
Cohort 5 SAD placebo	Placebo comparator	Dose: 10 mg A4250 matching placebo. Receives: Drug: Placebo
Cohort 1 MAD - 1 mg A4250 qd	Experimental	Dose: 1 mg A4250 qd for 7 days. Receives: Drug: A4250
Cohort 1 MAD placebo	Placebo comparator	Dose: 1 mg A4250 matching placebo qd for 7 days. Receives: Drug: Placebo
Cohort 2 MAD - 3 mg A4250	Experimental	Dose: 3 mg A4250 qd for 7 days Receives: Drug: A4250
Cohort 2 MAD placebo	Placebo comparator	Dose: 3 mg A4250 matching placebo qd for 7 days. Receives: Drug: Placebo
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. Receives: Drug: A4250
Cohort 3 MAD placebo	Placebo comparator	Dose: 1.5 A4250 matching placebo b.i.d for 7 days. Receives: Drug: Placebo
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. Receives: Drug: A4250; Drug: Questran
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. Receives: Drug: Questran; Drug: Placebo
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. Receives: Drug: A4250; Drug: CRC (A3384)
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 Receives: Drug: Placebo
Cohort 6 MAD - 1 g CRC	Active comparator	Dose: 1 g CRC b.i.d Receives: Drug: CRC (A3384)
Cohort 6 MAD CRC placebo	Placebo comparator	Dose: 1 g CRC matching placebo b.i.d. Receives: Drug: Placebo
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 Receives: Drug: A4250; Drug: CRC (A3384)
Cohort 7 MAD A4250 placebo + CRC placebo	Placebo comparator	Dose: 3 mg A4250 matching placebo qd + 1 g CRC matching placebo b.i.d. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean (± SD) Plasma Pharmacokinetic Concentrations of A4250 Following A Single Oral 10 mg A4250 Dose - Tmax
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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 4 h compared to pre-dose
Measured: 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
Measured: 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
Measured: AUC(0-12) on Day 7 (only for Part II)
Geometric (geometric CV%) Mean for AUC(0-12) on Day 7 for plasma C4
Measured: 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
Measured: 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
Measured: 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
Measured: Change from Day 1 Pre-dose to Day 7 at 24 hours Post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2013May 2014

First posted15 Nov 2016 (estimated)
Study startJul 2013
Primary completionMay 2014
Study completionMay 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Orphan Cholestatic Liver DiseasesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 94 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02963077
Sponsor's protocol ID: A4250-001
Other IDs: 2013-001175-21
Status last verified: Mar 2024
First submitted: 1 Nov 2016
Last updated: 7 Mar 2024
Results posted: No
Data monitoring committee: No
Individual data sharing: No