NCT02963077

Brief 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.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
94

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jul 2013

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2013

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2014

Completed
2.5 years until next milestone

First Submitted

Initial submission to the registry

November 1, 2016

Completed
14 days until next milestone

First Posted

Study publicly available on registry

November 15, 2016

Completed
Last Updated

March 7, 2024

Status Verified

March 1, 2024

Enrollment Period

10 months

First QC Date

November 1, 2016

Last Update Submit

March 6, 2024

Conditions

Orphan Cholestatic Liver DiseasesPrimary Biliary CirrhosisProgressive Familial Intrahepatic CholestasisAlagille Syndrome

Outcome Measures

Primary Outcomes (14)

  • 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

  • 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

  • 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

  • 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).

  • 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).

  • 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).

  • 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).

  • 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.

  • 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.

  • Geometric (geometric CV%) Mean for AUC(0-12) on Day 7 for plasma FGF19

    AUC(0-12) on Day 7 (only for Part II)

  • Geometric (geometric CV%) Mean for AUC(0-12) on Day 7 for plasma C4

    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

    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

    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

    Change from Day 1 Pre-dose to Day 7 at 24 hours Post-dose

Study Arms (24)

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).

Drug: A4250

Cohort 2 SAD - 0.3 mg A4250

EXPERIMENTAL

Dose: 0.3 mg of A4250.

Drug: A4250

Cohort 3 SAD - 1 mg A4250

EXPERIMENTAL

Dose: 1 mg A4250.

Drug: A4250

Cohort 4 SAD - 3 mg A4250

EXPERIMENTAL

Dose: 3 mg A4250.

Drug: A4250

Cohort 5 SAD - 10 mg A4250

EXPERIMENTAL

Dose: 10 mg A4250.

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).

Drug: Placebo

Cohort 2 SAD placebo

PLACEBO COMPARATOR

Dose: 0.3 mg A4250 matching placebo.

Drug: Placebo

Cohort 3 SAD placebo

PLACEBO COMPARATOR

Dose: 1 mg A4250 matching placebo.

Drug: Placebo

Cohort 4 SAD placebo

PLACEBO COMPARATOR

Dose: 3 mg A4250 matching placebo.

Drug: Placebo

Cohort 5 SAD placebo

PLACEBO COMPARATOR

Dose: 10 mg A4250 matching placebo.

Drug: Placebo

Cohort 1 MAD - 1 mg A4250 qd

EXPERIMENTAL

Dose: 1 mg A4250 qd for 7 days.

Drug: A4250

Cohort 1 MAD placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Cohort 2 MAD - 3 mg A4250

EXPERIMENTAL

Dose: 3 mg A4250 qd for 7 days

Drug: A4250

Cohort 2 MAD placebo

PLACEBO COMPARATOR

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

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.

Drug: A4250

Cohort 3 MAD placebo

PLACEBO COMPARATOR

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

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.

Drug: A4250Drug: 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.

Drug: QuestranDrug: 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.

Drug: A4250Drug: 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

Drug: Placebo

Cohort 6 MAD - 1 g CRC

ACTIVE COMPARATOR

Dose: 1 g CRC b.i.d

Drug: CRC (A3384)

Cohort 6 MAD CRC placebo

PLACEBO COMPARATOR

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

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

Drug: A4250Drug: 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.

Drug: Placebo

Interventions

A4250DRUG
Cohort 1 MAD - 1 mg A4250 qdCohort 1 SAD - 0.1 mg A4250Cohort 2 MAD - 3 mg A4250Cohort 2 SAD - 0.3 mg A4250Cohort 3 MAD - 1.5 mg A4250 b.i.d for 7 days.Cohort 3 SAD - 1 mg A4250Cohort 4 MAD - 3 mg A4250 qd + 1 mg Questran b.i.dCohort 4 SAD - 3 mg A4250Cohort 5 MAD - 3 mg A4250 qd + 1 g CRC b.i.dCohort 5 SAD - 10 mg A4250Cohort 7 MAD - 3 mg A4250 qd + 1 g CRC b.i.d
CRC (A3384)DRUG
Cohort 5 MAD - 3 mg A4250 qd + 1 g CRC b.i.dCohort 6 MAD - 1 g CRCCohort 7 MAD - 3 mg A4250 qd + 1 g CRC b.i.d
QuestranDRUG
Cohort 4 MAD - 3 mg A4250 qd + 1 mg Questran b.i.dCohort 4 MAD A4250 placebo + 1 mg Questran b.i.d
PlaceboDRUG
Cohort 1 MAD placeboCohort 1 SAD placeboCohort 2 MAD placeboCohort 2 SAD placeboCohort 3 MAD placeboCohort 3 SAD placeboCohort 4 MAD A4250 placebo + 1 mg Questran b.i.dCohort 4 SAD placeboCohort 5 MAD A4250 placebo + CRC placeboCohort 5 SAD placeboCohort 6 MAD CRC placeboCohort 7 MAD A4250 placebo + CRC placebo

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Liver Cirrhosis, BiliaryCholestasis, progressive familial intrahepatic 1Alagille Syndrome

Interventions

Cholestyramine Resin

Condition Hierarchy (Ancestors)

Cholestasis, IntrahepaticCholestasisBile Duct DiseasesBiliary Tract DiseasesDigestive System DiseasesLiver DiseasesLiver CirrhosisFibrosisPathologic ProcessesPathological Conditions, Signs and SymptomsHeart Defects, CongenitalCardiovascular AbnormalitiesCardiovascular DiseasesAbnormalities, MultipleCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGenetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

PolystyrenesPlasticsPolymersMacromolecular SubstancesBiomedical and Dental MaterialsManufactured MaterialsTechnology, Industry, and Agriculture

Study Officials

  • Ipsen Medical Director

    Ipsen

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 1, 2016

First Posted

November 15, 2016

Study Start

July 1, 2013

Primary Completion

May 1, 2014

Study Completion

May 1, 2014

Last Updated

March 7, 2024

Record last verified: 2024-03

Data Sharing

IPD Sharing
Will not share