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

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Biliary Cirrhosis; Alagille Syndrome; Progressive Familial Intrahepatic Cholestasis; Orphan Cholestatic Liver Diseases
• Intervention / Treatment: Drug: 3 mg [14C]-A4250 capsule

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham
    • Ruddington, Nottingham, United Kingdom, NG11 6JS
      • Quotient Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3 mg [14C]-A4250 capsule	Drug: 3 mg [14C]-A4250 capsule; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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))
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)	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))
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	Between pre-dose and up to 48 hours post dose
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	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))
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	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))

Collaborators and Investigators

• Sponsor: Albireo
• Investigators: Study Director: Ipsen Medical Director, Ipsen

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2017
• Primary Completion (Actual): March 8, 2017
• Study Completion (Actual): March 8, 2017

Study Registration Dates

• First Submitted: February 27, 2017
• First Submitted That Met QC Criteria: March 13, 2017
• First Posted (Actual): March 17, 2017

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Fibrosis; Biliary Tract Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Abnormalities, Multiple; Bile Duct Diseases; Liver Cirrhosis; Liver Diseases; Cholestasis; Liver Cirrhosis, Biliary; Cholestasis, Intrahepatic; Alagille Syndrome
• Other Study ID Numbers: A4250-007; 2016-002923-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No