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

A

Albireo

Status and phase

Completed
Phase 1

Conditions

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

Treatments

Drug: Questran
Drug: A4250
Drug: CRC (A3384)
Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT02963077
2013-001175-21 (EudraCT Number)
A4250-001

Details and patient eligibility

About

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.

Enrollment

94 patients

Sex

All

Ages

18 to 60 years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

94 participants in 24 patient groups, including a placebo group

Cohort 1 SAD - 0.1 mg A4250
Experimental group
Description:
Dose: 0.1 mg of A4250. Sentinel dosing was used (2 sub-cohorts dosed a minimum of 24 h apart).
Treatment:
Drug: A4250
Cohort 2 SAD - 0.3 mg A4250
Experimental group
Description:
Dose: 0.3 mg of A4250.
Treatment:
Drug: A4250
Cohort 3 SAD - 1 mg A4250
Experimental group
Description:
Dose: 1 mg A4250.
Treatment:
Drug: A4250
Cohort 4 SAD - 3 mg A4250
Experimental group
Description:
Dose: 3 mg A4250.
Treatment:
Drug: A4250
Cohort 5 SAD - 10 mg A4250
Experimental group
Description:
Dose: 10 mg A4250.
Treatment:
Drug: A4250
Cohort 1 SAD placebo
Placebo Comparator group
Description:
Dose: 0.1 mg of A4250 matching placebo. Sentinel dosing was used (2 sub-cohorts dosed a minimum of 24 h apart).
Treatment:
Drug: Placebo
Cohort 2 SAD placebo
Placebo Comparator group
Description:
Dose: 0.3 mg A4250 matching placebo.
Treatment:
Drug: Placebo
Cohort 3 SAD placebo
Placebo Comparator group
Description:
Dose: 1 mg A4250 matching placebo.
Treatment:
Drug: Placebo
Cohort 4 SAD placebo
Placebo Comparator group
Description:
Dose: 3 mg A4250 matching placebo.
Treatment:
Drug: Placebo
Cohort 5 SAD placebo
Placebo Comparator group
Description:
Dose: 10 mg A4250 matching placebo.
Treatment:
Drug: Placebo
Cohort 1 MAD - 1 mg A4250 qd
Experimental group
Description:
Dose: 1 mg A4250 qd for 7 days.
Treatment:
Drug: A4250
Cohort 1 MAD placebo
Placebo Comparator group
Description:
Dose: 1 mg A4250 matching placebo qd for 7 days.
Treatment:
Drug: Placebo
Cohort 2 MAD - 3 mg A4250
Experimental group
Description:
Dose: 3 mg A4250 qd for 7 days
Treatment:
Drug: A4250
Cohort 2 MAD placebo
Placebo Comparator group
Description:
Dose: 3 mg A4250 matching placebo qd for 7 days.
Treatment:
Drug: Placebo
Cohort 3 MAD - 1.5 mg A4250 b.i.d for 7 days.
Experimental group
Description:
Dose: 1.5 mg A4250 b.i.d. for 7 days.
Treatment:
Drug: A4250
Cohort 3 MAD placebo
Placebo Comparator group
Description:
Dose: 1.5 A4250 matching placebo b.i.d for 7 days.
Treatment:
Drug: Placebo
Cohort 4 MAD - 3 mg A4250 qd + 1 mg Questran b.i.d
Experimental group
Description:
Dose: 3 mg A4250 qd + 1 mg Questran b.i.d for 7 days.
Treatment:
Drug: A4250
Drug: Questran
Cohort 4 MAD A4250 placebo + 1 mg Questran b.i.d
Active Comparator group
Description:
Dose: 3 mg A4250 matching placebo + 1 mg Questran b.i.d for 7 days.
Treatment:
Drug: Placebo
Drug: Questran
Cohort 5 MAD - 3 mg A4250 qd + 1 g CRC b.i.d
Experimental group
Description:
Dose: 3 mg A4250 qd + 1 g CRC b.i.d for 7 days.
Treatment:
Drug: CRC (A3384)
Drug: A4250
Cohort 5 MAD A4250 placebo + CRC placebo
Placebo Comparator group
Description:
Dose: 3 mg A4250 matching placebo qd + 1 g CRC placebo b.i.d for 7 days
Treatment:
Drug: Placebo
Cohort 6 MAD - 1 g CRC
Active Comparator group
Description:
Dose: 1 g CRC b.i.d
Treatment:
Drug: CRC (A3384)
Cohort 6 MAD CRC placebo
Placebo Comparator group
Description:
Dose: 1 g CRC matching placebo b.i.d.
Treatment:
Drug: Placebo
Cohort 7 MAD - 3 mg A4250 qd + 1 g CRC b.i.d
Experimental group
Description:
Dose: 3 mg A4250 qd + 1 g CRC b.i.d
Treatment:
Drug: CRC (A3384)
Drug: A4250
Cohort 7 MAD A4250 placebo + CRC placebo
Placebo Comparator group
Description:
Dose: 3 mg A4250 matching placebo qd + 1 g CRC matching placebo b.i.d.
Treatment:
Drug: Placebo

Trial contacts and locations

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Data sourced from clinicaltrials.gov

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