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

NCT ID: NCT02963077

Last Updated: 2024-03-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

94 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-31

Study Completion Date

2014-05-31

Brief Summary

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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.

Detailed Description

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Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Cohort 1 SAD - 0.1 mg A4250

Dose: 0.1 mg of A4250. Sentinel dosing was used (2 sub-cohorts dosed a minimum of 24 h apart).

Group Type EXPERIMENTAL

A4250

Intervention Type DRUG

Cohort 2 SAD - 0.3 mg A4250

Dose: 0.3 mg of A4250.

Group Type EXPERIMENTAL

A4250

Intervention Type DRUG

Cohort 3 SAD - 1 mg A4250

Dose: 1 mg A4250.

Group Type EXPERIMENTAL

A4250

Intervention Type DRUG

Cohort 4 SAD - 3 mg A4250

Dose: 3 mg A4250.

Group Type EXPERIMENTAL

A4250

Intervention Type DRUG

Cohort 5 SAD - 10 mg A4250

Dose: 10 mg A4250.

Group Type EXPERIMENTAL

A4250

Intervention Type DRUG

Cohort 1 SAD placebo

Dose: 0.1 mg of A4250 matching placebo. Sentinel dosing was used (2 sub-cohorts dosed a minimum of 24 h apart).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Cohort 2 SAD placebo

Dose: 0.3 mg A4250 matching placebo.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Cohort 3 SAD placebo

Dose: 1 mg A4250 matching placebo.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Cohort 4 SAD placebo

Dose: 3 mg A4250 matching placebo.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Cohort 5 SAD placebo

Dose: 10 mg A4250 matching placebo.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Cohort 1 MAD - 1 mg A4250 qd

Dose: 1 mg A4250 qd for 7 days.

Group Type EXPERIMENTAL

A4250

Intervention Type DRUG

Cohort 1 MAD placebo

Dose: 1 mg A4250 matching placebo qd for 7 days.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Cohort 2 MAD - 3 mg A4250

Dose: 3 mg A4250 qd for 7 days

Group Type EXPERIMENTAL

A4250

Intervention Type DRUG

Cohort 2 MAD placebo

Dose: 3 mg A4250 matching placebo qd for 7 days.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Cohort 3 MAD - 1.5 mg A4250 b.i.d for 7 days.

Dose: 1.5 mg A4250 b.i.d. for 7 days.

Group Type EXPERIMENTAL

A4250

Intervention Type DRUG

Cohort 3 MAD placebo

Dose: 1.5 A4250 matching placebo b.i.d for 7 days.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Cohort 4 MAD - 3 mg A4250 qd + 1 mg Questran b.i.d

Dose: 3 mg A4250 qd + 1 mg Questran b.i.d for 7 days.

Group Type EXPERIMENTAL

A4250

Intervention Type DRUG

Questran

Intervention Type DRUG

Cohort 4 MAD A4250 placebo + 1 mg Questran b.i.d

Dose: 3 mg A4250 matching placebo + 1 mg Questran b.i.d for 7 days.

Group Type ACTIVE_COMPARATOR

Questran

Intervention Type DRUG

Placebo

Intervention Type DRUG

Cohort 5 MAD - 3 mg A4250 qd + 1 g CRC b.i.d

Dose: 3 mg A4250 qd + 1 g CRC b.i.d for 7 days.

Group Type EXPERIMENTAL

A4250

Intervention Type DRUG

CRC (A3384)

Intervention Type DRUG

Cohort 5 MAD A4250 placebo + CRC placebo

Dose: 3 mg A4250 matching placebo qd + 1 g CRC placebo b.i.d for 7 days

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Cohort 6 MAD - 1 g CRC

Dose: 1 g CRC b.i.d

Group Type ACTIVE_COMPARATOR

CRC (A3384)

Intervention Type DRUG

Cohort 6 MAD CRC placebo

Dose: 1 g CRC matching placebo b.i.d.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Cohort 7 MAD - 3 mg A4250 qd + 1 g CRC b.i.d

Dose: 3 mg A4250 qd + 1 g CRC b.i.d

Group Type EXPERIMENTAL

A4250

Intervention Type DRUG

CRC (A3384)

Intervention Type DRUG

Cohort 7 MAD A4250 placebo + CRC placebo

Dose: 3 mg A4250 matching placebo qd + 1 g CRC matching placebo b.i.d.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Interventions

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A4250

Intervention Type DRUG

CRC (A3384)

Intervention Type DRUG

Questran

Intervention Type DRUG

Placebo

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Albireo

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Other Identifiers

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2013-001175-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

A4250-001

Identifier Type: -

Identifier Source: org_study_id

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