Drug-Drug Interaction (DDI) Study of ALXN2050 in Healthy Adult Participants

A Three-Part Phase 1 Study to Evaluate the Potential Drug Interactions Between ALXN2050 and Cyclosporine, Tacrolimus, and Mycophenolate Mofetil in Healthy Adult Participants

This study will evaluate the potential drug interactions between ALXN2050 and cyclosporine (Part 1), between ALXN2050 and tacrolimus (Part 2), and between ALXN2050 and mycophenolate mofetil (MMF) (Part 3).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ALXN2050; Drug: Cyclosporine; Drug: Tacrolimus; Drug: MMF

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Clinical Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Medically healthy with no clinically significant or relevant abnormalities as determined by medical history, physical or neurological examination, vital signs, 12-lead electrocardiogram, screening clinical laboratory profiles (hematology, biochemistry, coagulation, and urinalysis), as deemed by the Investigator or designee at Screening.
• Body mass index within the range 18.0 to 32.0 kilograms (kg)/meter^2, inclusive, with a minimum body weight of 50.0 kg at Screening.

Exclusion Criteria:

• History of any medical or psychiatric condition or disease that might limit the participant's ability to complete or participate in this clinical study, confound the results of the study, or pose an additional risk to the participant by their participation in the study.
• Participation in another investigational drug or investigational device study within 5 half- lives (if known) or 30 days prior to the first dose of study intervention, whichever is longer.
• History of drug or alcohol abuse within 2 years prior to the first dose of study intervention or positive drugs-of-abuse or alcohol screen at Screening or Day -1; current tobacco users or smokers or a positive cotinine test at Screening.
• Donation of whole blood from 3 months prior to the first dose of study intervention, or of plasma from 30 days prior to the first dose of study intervention; receipt of blood products within 6 months prior to the first dose of study intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - Cyclosporine; Participants will receive ALXN2050 and cyclosporine in a fixed sequence over 3 periods. Period 1: Participants will receive multiple doses of ALXN2050. Period 2: Participants will receive multiple doses of cyclosporine. Period 3: Participants will receive multiple doses of ALXN2050 co-administered with multiple doses of cyclosporine. There will be a washout period between the last dose of ALXN2050 in Period 1 and the first dose of cyclosporine in Period 2 and between the last dose of cyclosporine in Period 2 and the first dosing in Period 3.	Drug: ALXN2050; Oral tablet.; Other Names: ACH-0145228 (formerly); Drug: Cyclosporine; Oral capsule.
Experimental: Part 2 - Tacrolimus; Participants will receive tacrolimus and ALXN2050 in a fixed sequence over 2 periods. Period 1: Participants will receive a single dose of tacrolimus. Period 2: Participants will receive multiple doses of ALXN2050 alone and co-administered with a single dose of tacrolimus. There will be a washout period between the dose of tacrolimus in Period 1 and the first dose of ALXN2050 in Period 2.	Drug: ALXN2050; Oral tablet.; Other Names: ACH-0145228 (formerly); Drug: Tacrolimus; Oral capsule.
Experimental: Part 3 - MMF; Participants will receive MMF and ALXN2050 in a fixed sequence over 2 periods. Period 1: Participants will receive a single dose of MMF. Period 2: Participants will receive multiple doses of ALXN2050 alone and co-administered with a single dose of MMF. There will be a washout period between the dose of MMF in Period 1 and the first dose of ALXN2050 in Period 2.	Drug: ALXN2050; Oral tablet.; Other Names: ACH-0145228 (formerly); Drug: MMF; Oral tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1 Cyclosporine: Area Under The Concentration-Time Curve From Time Zero To The 12-hour Time Point (AUC0-12) Following Multiple Dose Cyclosporine Alone Versus When Dosed In The Presence Of Steady-state ALXN2050	Up to 72 hours postdose
Part 1: ALXN2050 AUC0-12 Following Multiple Dose ALXN2050 When Dosed Alone Versus When Dosed In The Presence Of Steady-state Cyclosporine	Up to 72 hours postdose
Part 1: Cyclosporine Maximum Observed Concentration (Cmax) Following Multiple Dose Cyclosporine When Dosed Alone Versus When Dosed In The Presence Of Steady-state ALXN2050	Up to 72 hours postdose
Part 1: ALXN2050 Cmax Following Multiple Dose ALXN2050 When Dosed Alone Versus When Dosed In The Presence Of Steady-state Cyclosporine	Up to 72 hours postdose
Part 1: Cyclosporine Time To Maximum Plasma Concentration (Tmax) Following Multiple Dose Cyclosporine When Dosed Alone Versus When Dosed In The Presence Of Steady-state ALXN2050	Up to 72 hours postdose
Part 1: ALXN2050 Tmax Following Multiple Dose ALXN2050 When Dosed Alone Versus When Dosed In The Presence Of Steady-state Cyclosporine	Up to 72 hours postdose
Part 2: Tacrolimus Area Under The Concentration-Time Curve From Time Zero To The Last Observed Concentration (AUC0-t) Following Single Dose Tacrolimus When Dosed Alone Versus When Dosed In The Presence Of Steady-state ALXN2050	Up to 144 hours postdose
Part 2: Tacrolimus Area Under the Concentration-Time Curve From Time Zero To Infinity (AUC0-inf) Following Single Dose Tacrolimus When Dosed Alone Versus When Dosed In The Presence of Steady-state ALXN2050	Up to 144 hours postdose
Part 2: Tacrolimus Cmax Following Single Dose Tacrolimus When Dosed Alone Versus When Dosed In The Presence Of Steady-state ALXN2050	Up to 144 hours postdose
Part 2: Tacrolimus Tmax Following Single Dose Tacrolimus When Dosed Alone Versus When Dosed In The Presence Of Steady-state ALXN2050	Up to 144 hours postdose
Part 3: Mycophenolic Acid (MPA) And Mycophenolic Acid Glucuronide (MPAG) (Active Metabolites Of MMF) AUC0-t Following Single Dose MMF When Dosed Alone Versus When Dosed In The Presence Of Steady-state ALXN2050	Up to 72 hours postdose
Part 3: MPA and MPAG AUC0-inf Following Single Dose MMF When Dosed Alone Versus When Dosed In The Presence Of Steady-State ALXN2050	Up to 72 hours postdose
Part 3: MPA And MPAG Cmax Following Single Dose MMF When Dosed Alone Versus When Dosed In The Presence Of Steady-state ALXN2050	Up to 72 hours postdose
Part 3: MPA And MPAG Tmax Following Single Dose MMF When Dosed Alone Versus When Dosed In The Presence Of Steady-state ALXN2050	Up to 72 hours postdose

Secondary Outcome Measures

Outcome Measure	Time Frame
Parts 1-3: Number of Participants Experiencing Treatment-emergent Adverse Events	Day 1 through up to 12 days postdose

Collaborators and Investigators

• Sponsor: Alexion

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2022
• Primary Completion (Actual): March 21, 2022
• Study Completion (Actual): March 21, 2022

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 21, 2022

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Tacrolimus; Mycophenolate Mofetil; Factor D Inhibitor; Cyclosporine; Drug-Drug Interaction; ALXN2050
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Tacrolimus; Cyclosporine; Cyclosporins
• Other Study ID Numbers: ALXN2050-HV-110

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; CSR

Drug and device information, study documents

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