A Study to Evaluate Potential Drug Interactions Between ALXN2080 and Itraconazole, Fluconazole & Carbamazepine in Healthy Adults

A Phase 1 Study to Evaluate the Potential Drug Interactions Between ALXN2080 and Itraconazole, Fluconazole, and Carbamazepine in Healthy Adult Participants

The primary objectives of this study are to determine the effect of multiple doses of itraconazole on the single dose PK of ALXN2080, to determine the effect of multiple doses of fluconazole on the single dose PK of ALXN2080 (optional), and to determine the effect of multiple doses of carbamazepine on the single dose PK of ALXN2080.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ALXN2080; Drug: Itraconazole; Drug: Fluconazole (AxMP); Drug: Carbamazepine (AxMP)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Ruddington, United Kingdom, NG11 6JS
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy males or non-pregnant, non-lactating healthy females.
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, vital signs, triplicate 12-lead ECG, screening clinical laboratory profiles (hematology, clinical chemistry, coagulation, and urinalysis), as deemed by the Investigator or designee.
• Female participants of childbearing potential and male participants must follow protocol-specified contraception guidance
• BMI within the range of 18.0 to 32.0 kg/m2 (inclusive) and a minimum body weight of 50.0 kg at screening.

Exclusion Criteria:

• History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, neurological, psychiatric or other disorders; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
• History of meningococcal infection.
• History of additional risk factors for Torsades de Pointes (eg, heart failure, hypokalemia, family history of Long QT syndrome).
• History of unexplained, recurrent infection, or infection requiring treatment with systemic antibiotics within 14 days prior to Period 1 Day 1.
• History of significant multiple and/or severe allergies (hay fever is allowed unless it is active), including significant hypersensitivity reactions to commonly used antibacterial agents, including beta-lactams, penicillin, amoxicillin, aminopenicillin, fluoroquinolones (specifically including ciprofloxacin), cephalosporins, and carbapenems, which in the opinion of the Investigator would make it difficult to provide empiric antibiotic therapy or treat an active infection.
• Diseases or conditions or previous procedures known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• History of malignancy within 5 years prior to screening, with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence.
• Known hepatic or biliary abnormalities (including participants with Gilbert's syndrome).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; During Part 1, Period 1, participants will receive a single dose of ALXN2080 on the morning of Day 1. In Part 1, Period 2, participants will receive a dose of itraconazole orally once daily on the morning of Day 1 to Day 13. On the morning of Day 5, participants will be given a single dose of ALXN2080 co-administered with itraconazole.	Drug: ALXN2080; Participants will receive ALXN2080 orally.; Drug: Itraconazole; Participants will receive Itraconazole orally.
Experimental: Part 2 (Optional); During Part 2, Period 1, participants will receive a single dose of ALXN2080 on the morning of Day 1. In Part 2, Period 2, participants will receive a single loading dose of fluconazole, followed by a dose of fluconazole qd on the morning of Day 2 to Day 10. On the morning of Day 4, participants will be given a single dose of ALXN2080 co-administered with fluconazole.	Drug: ALXN2080; Participants will receive ALXN2080 orally.; Drug: Fluconazole (AxMP); Participants will receive Fluconazole orally.
Experimental: Part 3; During Part 3, Period 1 participants will receive a single dose of ALXN2080 on the morning of Day 1. In Part 3, Period 2, participants will receive a dose of carbamazepine bid on the morning and evening of Day 1 to Day 3, followed by a dose of carbamazepine bid on the morning and evening of Day 4 to Day 6 and a dose of carbamazepine bid on the morning and evening of Day 7 to Day 23. On the morning of Day 19, participants will be given a single dose of ALXN2080 co-administered with carbamazepine.	Drug: ALXN2080; Participants will receive ALXN2080 orally.; Drug: Carbamazepine (AxMP); Participants will receive Carbamazepine orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of ALXN2080	Day 1 up to Day 24
Area Under the Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-last) of ALXN2080	Day 1 up to Day 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax of Itraconazole	Day 4 up to Day 6
Area under the Curve for the Defined Interval Between Doses AUC(tau) of Itraconazole	Day 4 up to Day 6
Cmax of Fluconazole	Day 2 up to Day 5
AUC(tau) of Fluconazole	Day 2 up to Day 5
Cmax of Carbamazepine	Day 2 up to Day 20
AUC(tau) of Carbamazepine	Day 2 up to Day 20
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Baseline up to Day 34

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2024
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): May 16, 2024

Study Registration Dates

• First Submitted: December 5, 2023
• First Submitted That Met QC Criteria: December 8, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): June 20, 2024
• Last Update Submitted That Met QC Criteria: June 17, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Fluconazole; carbamazepine; itraconazole; ALXN2080
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones, Hormone Substitutes, and Hormone Antagonists; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Anticonvulsants; Sodium Channel Blockers; Antimanic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Itraconazole; Fluconazole; Carbamazepine
• Other Study ID Numbers: D7420C00003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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