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

NCT03082937 | Completed Phase 1

• 2 other identifiers: A4250-0072016-002923-27
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (5)

• 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))

Study Arms (1)

3 mg [14C]-A4250 capsule

EXPERIMENTAL

Drug: 3 mg [14C]-A4250 capsule

Interventions

3 mg [14C]-A4250 capsule DRUG

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.

3 mg [14C]-A4250 capsule

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Albireo: lead

Study Sites (1)

Quotient Clinical

Ruddington, Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Cholestasis, progressive familial intrahepatic 1; Alagille Syndrome; Liver Cirrhosis, Biliary

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2017
• First Posted: March 17, 2017
• Study Start: January 31, 2017
• Primary Completion: March 8, 2017
• Study Completion: March 8, 2017
• Last Updated: March 7, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)