An Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects
Phase 1
Completed
- Conditions
- Orphan Cholestatic Liver DiseasesProgressive Familial Intrahepatic CholestasisAlagille SyndromePrimary Biliary Cirrhosis
- Interventions
- Drug: 3 mg [14C]-A4250 capsule
- Registration Number
- NCT03082937
- Lead Sponsor
- Albireo
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 6
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 3 mg [14C]-A4250 capsule 3 mg [14C]-A4250 capsule -
- Primary Outcome Measures
Name Time Method Metabolite profiling of A4250 of faeces using liquid-chromatography-radio-detection with subsequent mass spectrometry as appropriate 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)) Identification of the chemical structure of each metabolite accounting for greater than 10% of the dose in faeces
To assess mass balance recovery of total radioactivity in urine 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)) 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 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)) 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 Between pre-dose and up to 48 hours post dose 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 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)) Identification of the chemical structure of each metabolite accounting for greater than 10% of the dose in urine
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Quotient Clinical
🇬🇧Ruddington, Nottingham, United Kingdom