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An Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects

Primary Purpose

Orphan Cholestatic Liver Diseases, Progressive Familial Intrahepatic Cholestasis, Alagille Syndrome

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
3 mg [14C]-A4250 capsule
Sponsored by
Albireo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Orphan Cholestatic Liver Diseases

Eligibility Criteria

30 Years - 65 Years (Adult, Older Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

  1. Healthy males
  2. Age 30 to 65 years of age
  3. Body mass index of 18.0 to 35.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
  4. Must be willing and able to communicate and participate in the whole study
  5. Must have regular bowel movements (i.e., average stool production of ≥1 and ≤3 stools per day)
  6. Must provide written informed consent
  7. Must agree to use an adequate method of contraception

Exclusion Criteria:

  1. Subjects who have received any IMP in a clinical research study within the previous 3 months prior to screening
  2. Subjects who are study site employees, or immediate family members of a study site or sponsor employee
  3. Subjects who have 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 (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
  6. Current smokers and those who have smoked within the last 12 months. A confirmed positive urine cotinine test at screening or admission
  7. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
  8. Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999, shall participate in the study
  9. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
  10. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator
  11. Confirmed positive drugs of abuse test result at screening or admission
  12. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
  13. Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <90 mL/min using the Cockcroft-Gault equation
  14. History of cardiovascular, renal, hepatic, chronic respiratory or GI disease as judged by the investigator
  15. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
  16. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active
  17. Donation or loss of greater than 400 mL of blood within the previous 3 months
  18. Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 g per day paracetamol) or herbal remedies in the 14 days before IMP administration. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI and sponsor's medical monitor.
  19. Failure to satisfy the investigator of fitness to participate for any other reason

Sites / Locations

  • Quotient Clinical

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

3 mg [14C]-A4250 capsule

Arm Description

Outcomes

Primary Outcome Measures

To assess mass balance recovery of total radioactivity in urine
Amount excreted (Ae) and Ae as a percentage of the administered dose (% Ae), cumulative recovery (CumAe) and cumulative recovery expressed as a percentage of the dose (Cum%Ae)
To assess mass balance recovery of total radioactivity in faeces
Amount excreted (Ae) and Ae as a percentage of the administered dose (% Ae), cumulative recovery (CumAe) and cumulative recovery expressed as a percentage of the dose (Cum%Ae)
Metabolite profiling of A4250 of plasma using liquid-chromatography-radio-detection with subsequent mass spectrometry as appropriate
Identification of the chemical structure of each metabolite accounting for greater than 10% of circulating radioactivity in plasma
Metabolite profiling of A4250 of urine using liquid-chromatography-radio-detection with subsequent mass spectrometry as appropriate
Identification of the chemical structure of each metabolite accounting for greater than 10% of the dose in urine
Metabolite profiling of A4250 of faeces using liquid-chromatography-radio-detection with subsequent mass spectrometry as appropriate
Identification of the chemical structure of each metabolite accounting for greater than 10% of the dose in faeces

Secondary Outcome Measures

Full Information

First Posted
February 27, 2017
Last Updated
March 13, 2017
Sponsor
Albireo
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1. Study Identification

Unique Protocol Identification Number
NCT03082937
Brief Title
An Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects
Official Title
An Open Label, Single-Dose, Single Period Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-A4250 in Healthy Male Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
January 31, 2017 (Actual)
Primary Completion Date
March 8, 2017 (Actual)
Study Completion Date
March 8, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Albireo

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objectives of the study are to assess the mass balance recovery after a single dose of carbon-14 [14C]-A4250 as a capsule and to provide plasma, urine and faecal samples for metabolite profiling and structural identification in healthy male subjects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Orphan Cholestatic Liver Diseases, Progressive Familial Intrahepatic Cholestasis, Alagille Syndrome, Primary Biliary Cirrhosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
3 mg [14C]-A4250 capsule
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
3 mg [14C]-A4250 capsule
Intervention Description
Each subject will receive a single administration of 3 mg [14C]-A4250 capsule for oral administration containing not more than 4.3 MBq (116 μCi), in the fasted state.
Primary Outcome Measure Information:
Title
To assess mass balance recovery of total radioactivity in urine
Description
Amount excreted (Ae) and Ae as a percentage of the administered dose (% Ae), cumulative recovery (CumAe) and cumulative recovery expressed as a percentage of the dose (Cum%Ae)
Time Frame
Between pre-dose (admission to 0 hour) and post dose (ending on morning of discharge (up to day 10 depending on if mass balance cumulative recovery >90% or <1% of dose has been collected))
Title
To assess mass balance recovery of total radioactivity in faeces
Description
Amount excreted (Ae) and Ae as a percentage of the administered dose (% Ae), cumulative recovery (CumAe) and cumulative recovery expressed as a percentage of the dose (Cum%Ae)
Time Frame
Between pre-dose (admission to 0 hour) and post dose (ending on the morning of discharge (up to day 10 depending on if mass balance cumulative recovery >90% or <1% of dose has been collected))
Title
Metabolite profiling of A4250 of plasma using liquid-chromatography-radio-detection with subsequent mass spectrometry as appropriate
Description
Identification of the chemical structure of each metabolite accounting for greater than 10% of circulating radioactivity in plasma
Time Frame
Between pre-dose and up to 48 hours post dose
Title
Metabolite profiling of A4250 of urine using liquid-chromatography-radio-detection with subsequent mass spectrometry as appropriate
Description
Identification of the chemical structure of each metabolite accounting for greater than 10% of the dose in urine
Time Frame
Between pre-dose (admission to 0 hour) and post dose (ending on the morning of discharge (up to day 10 depending on if mass balance cumulative recovery >90% or <1% of dose has been collected))
Title
Metabolite profiling of A4250 of faeces using liquid-chromatography-radio-detection with subsequent mass spectrometry as appropriate
Description
Identification of the chemical structure of each metabolite accounting for greater than 10% of the dose in faeces
Time Frame
Between pre-dose (admission to 0 hour) and post dose (ending on the morning of discharge (up to day 10 depending on if mass balance cumulative recovery >90% or <1% of dose has been collected))

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy males Age 30 to 65 years of age Body mass index of 18.0 to 35.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator Must be willing and able to communicate and participate in the whole study Must have regular bowel movements (i.e., average stool production of ≥1 and ≤3 stools per day) Must provide written informed consent Must agree to use an adequate method of contraception Exclusion Criteria: Subjects who have received any IMP in a clinical research study within the previous 3 months prior to screening Subjects who are study site employees, or immediate family members of a study site or sponsor employee Subjects who have 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 (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) Current smokers and those who have smoked within the last 12 months. A confirmed positive urine cotinine test at screening or admission Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999, shall participate in the study Subjects who do 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 Confirmed positive drugs of abuse test result at screening or admission Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <90 mL/min using the Cockcroft-Gault equation 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 Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active Donation or loss of greater than 400 mL of blood within the previous 3 months Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 g per day paracetamol) or herbal remedies in the 14 days before IMP administration. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI and sponsor's medical monitor. Failure to satisfy the investigator of fitness to participate for any other reason
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mats Ekelund, MD
Organizational Affiliation
Albireo
Official's Role
Study Director
Facility Information:
Facility Name
Quotient Clinical
City
Ruddington
State/Province
Nottingham
ZIP/Postal Code
NG11 6JS
Country
United Kingdom

12. IPD Sharing Statement

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An Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects

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