Safety, tolerability, pharmacokinetics and pharmacodynamics of an oral formulation of A3907 Not Applicable
Conditions
Interventions
This trial will be conducted at a single treatment center. Part A is a double-blind, randomized, placebo-controlled, single ascending dose (SAD), sequential group design. Part B is a double-blind, ran
Sponsors
Albireo (Sweden)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Healthy male subjects and female subjects of nonchildbearing potential aged between 18 and 60 years (inclusive) with a body mass index between 18.0 and 32.0 kg/m² (inclusive)
Exclusion criteria
Exclusion criteria: 1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee) 2. History of any illness that, in the opinion of the investigator (or designee), might confound the results of the study or pose an additional risk to the subject by their participation in the study 3. Significant history of gastric retention, constipation, urinary retention, urinary obstruction or difficulty in voiding, as determined by the investigator (or designee) 4. History of narrow-angle glaucoma 5. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, including the active ingredient, excipients, or related compounds 6. History of stomach or intestinal surgery or resection or other medical condition that would potentially alter the absorption, metabolism, and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed) 7. Planned weight loss, being on any weight-reducing diet, or being on or planning to start any prescription or over-the-counter anti-obesity agent 8. Confirmed (e.g., two consecutive measurements separated by 10 minutes) systolic blood pressure >140 or 90 or 90 or 37.8°C or 1.5× ULN (upper limit of normal) 9.2. Total bilirubin >1.5× ULN (total bilirubin >1.5× ULN is acceptable if direct bilirubin 2× ULN 10. History or presence of clinically significant impaired renal function as indicated by abnormal creatinine, urea, or urinary constituents as determined by the investigator (or designee) or glomerular filtration rate of 21 units per week for males and >14 units for females. One unit of alcohol equals ½ pint (285 ml) of beer or lager, 1 glass (125 ml) of wine, or 1/6 gill (25 ml) of spirits 14. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at screening or check-in 15. Positive hepatitis B surface antigen or hepatitis C antibody test result within 3 months prior to dosing, or positive hepatitis panel or positive human immunodeficiency virus test at screening. Subjects with positive hepatitis C antibody due to prior resolved disease can be enrolled if a confirmatory hepatitis C RNA test is negative. 16. Participation in a clinical study involving administration of an investigational drug (new chemical entity) within 90 days prior to dosing or in >4 clinical studies within 12 months prior to dosing 17. Use or intent to use any me
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability assessed using: 1. Incidence and severity of adverse events. AEs are recorded during each visit: Part A: Screening (Days -28 to -2), Day -1, Day 1, Day 2, Day 3/ET Follow up Visit (Day 10±1) Part B: Screening (Days -28 to -2), Day -1, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9/ET Follow up Visit (Day 16±1) 2. Laboratory abnormalities (clinical chemistry, hematology, coagulation, urinalysis): Part A: Screening (Days -28 to -2), Day -1, Day 2, Day 3/ET Follow up Visit (Day 10±1) Part B: Screening (Days -28 to -2), Day -1, Day 2, Day 4, Day 7, Day 9/ET Follow up Visit (Day 16±1) 3. 12-lead ECG parameters obtained at predose, 1, 2, 4, and 8 hours post-dose. ECG predose will be measured in triplicate. All other measurements will be performed singly. Part A: Screening (Days -28 to -2), Day -1, Day 1, Day 2, Day 3/ET Follow up Visit (Day 10±1) Part B: Screening (Days -28 to -2), Day -1, Day 1, Day 3, Day 5, Day 7, Day 9/ET Follow up Visit (Day 16±1) 4. Vital signs measurements taken at predose, 1, 2, 4, and 8 hours post-dose: Part A: Screening (Days -28 to -2), Day -1, Day 1, Day 2, Day 3/ET Follow up Visit (Day 10±1) Part B: Screening (Days -28 to -2), Day -1, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9/ET Follow up Visit (Day 16±1) 5. Physical examinations: 5.1. Complete physical exam performed on screening day (days-28 to -2) and on day-1 5.2. Symptom-directed physical examination for part A (single dose) will be performed on day 1 and day 3/ET. Part B (multiple dose) will collect symptom-directed physicals on days: 1, 4, 7, 9/ET, and day 17 follow up 5.3. On dosing days the physical examination should be performed post-dose 6. Number of bowel | — |
Secondary
| Measure | Time frame |
|---|---|
| Blood and urine samples will be collected for the analysis of plasma and urinary concentrations of A3907. Pharmacokinetic parameters will be derived by noncompartmental analysis. For Part A, the PK parameters will include: 1. AUC from time zero to infinity (AUC0-8) 2. AUC from time zero to the time of the last quantifiable concentration (AUC0-tlast) •percentage of AUC that is due to extrapolation from the last quantifiable concentration to infinity (%AUCextrap) 3. AUC from time zero to 24 hours postdose (AUC0- 24) 4. Maximum observed concentration (Cmax) 5. Time of Cmax (tmax) 6. Apparent terminal elimination rate constant (?z) 7. Apparent terminal elimination half-life (t1/2) 8. Apparent total clearance (CL/F) 9. Apparent volume of distribution (Vz/F) 10. Amount of drug excreted in urine (Ae) 11. Percentage of dose recovered in urine (fe) 12. Renal clearance (CLR) In Part B, the PK parameters will include: 1. AUC over a dosing interval (AUC0-t) 2. Cmax 3. tmax 4. ?z 5. t1/2 6. CL/F 7. Vz/F 8. Observed accumulation ratio based on AUC0-t (ARAUC) 9. Ae 10. fe 11. CLR Measured using: 1. Urine intervals collected at 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours postdose 2. Blood samples collected predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose 3. Blood samples collected Day 1 predose and at 4 and 24 hours post-dose | — |
Countries
England, United Kingdom
Contacts
Public ContactAnna Wallebäck
Outcome results
None listed