Complement alternative pathway-mediated diseases Not Applicable
Conditions
Interventions
Different volunteers will be enrolled in Part 1 and Part 2. In Part 1, up to 30 volunteers will be split into 2 cohorts. Each cohort will receive up to 6 oral doses of the test medicine as different r
Sponsors
Alexion Pharmaceuticals (United States)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be 18 to 55 years inclusive at the time of signing the informed consent. 2. Healthy males or non-pregnant, non-lactating healthy females. 3. Participants who are overtly healthy as determined by medical evaluation including medical history, physical or neurological examination, vital signs, 12-lead ECG, screening clinical laboratory profiles (hematology, biochemistry, coagulation, and urinalysis), as deemed by the Investigator or designee. 4. BMI within the range of 18.0 to 30.0 kg/m² (inclusive), with a minimum body weight of 50.0 kg at screening. 5. Female participants of childbearing potential and male participants must follow protocol specified contraception guidance. 6. Capable of giving signed informed consent as described in the clinical protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
Exclusion criteria
Exclusion criteria: 1. History of clinically significant respiratory, cardiovascular, dermatological, hepatic, renal, GI, endocrinological, haematological, psychological, psychiatric, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data. 2. History of meningococcal infection. 3. History of clinically significant hypersensitivity reactions to commonly used antibacterial agents, including beta lactams, penicillin, aminopenicillins, fluoroquinolones (specifically including ciprofloxacin), cephalosporins, and carbapenems, which in the opinion of the Investigator would make it difficult to properly provide either empiric antibiotic therapy or treat an active infection. 4. History of clinically significant hypersensitivity or idiosyncratic reaction to the study drugs or related compounds. 5. History of significant multiple and/or severe allergies (eg, drug, latex allergy, band aids, adhesive dressing, or medical tape). Hay fever is allowed unless it is active. 6. History of seizures including childhood seizures. 7. History of significant head injury, or head trauma requiring medical evaluation. 8. History of malignancy within 5 years of screening, with the exception of non-melanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence. 9. Any previous procedure, including history of stomach or intestinal surgery or resection, cholecystectomy, gallstones, TIPS, or surgical shunt, that could alter absorption or excretion of orally administered drugs. 10. Significant current or chronic history of liver disease. 11. Known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome). 12. Participants who do not have suitable veins for multiple venipunctures/cannulation as assessed by the Investigator or delegate at screening 13. Participants who are taking, or have taken, any prescribed or over-the-counter drug or vitamins/herbal remedies (other than up to 4 g paracetamol per day, hormonal contraception and HRT) in the 14 days before first study intervention administration. COVID-19 vaccines are accepted concomitant medication. Exceptions may apply, as determined by the Investigator. 14. Participants who have taken any CYP or P-gp inhibitors or inducers within 14 days prior to first administration of study intervention. 15. Donation of whole blood or loss of greater than 400 mL of blood from 3 months prior to first dosing, or donation of plasma from 30 days before first dosing. 16. Receipt of blood products within 6 months prior to first dosing. 17. Participants who have received any study intervention (IMP) in a clinical research study within the 90 days, or less than 5 elimination half-lives, whichever is longer, prior to first planned dose. 18. Participants who have taken part in Part 1 are not permitted to take part in Part 2. 19. The following laboratory evaluations at screening, including: 19.1. Serum creatinine > upper limit of normal (ULN) 19.2. Alanine aminotransaminase (ALT) > ULN; Aspartate transaminase (AST) > ULN; Alkaline phosphatase (ALP) > ULN; or Total bilirubin > ULN 19.3. Hemoglobin (Hb) ULN, international normalized ratio > ULN reference range, or prothrombin time > ULN. 20. Evidence of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1 1.1. PK parameters for ALXN2050 including but not limited to: Cmax, Tmax, C24, Clast, AUC(0-24), AUC(0-last), AUC(0-inf) and T1/2. 1.2. Calculation of the relative bioavailability for Cmax, AUC(0-last) and AUC(0-inf) of the ALXN2050 MR prototype formulations compared with the IR tablet formulation. Part 2 2.1. PK parameters for ALXN2050 including but not limited to: Cmax, Tmax, Ctrough and AUC(0-tau). | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1 1.1. To provide additional safety and tolerability information for ALXN2050 by assessing: incidence of adverse events (AEs), physical examinations and change from baseline for vital signs, electrocardiograms (ECGs), and laboratory safety tests. Part 2 2.1. To provide additional safety and tolerability information for ALXN2050 by assessing: incidence of AEs, physical examinations and change from baseline for vital signs, ECGs, and laboratory safety tests. | — |
Countries
England, United Kingdom
Contacts
Public ContactSharan Sidhu
Outcome results
None listed