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

NCT05202145 | Completed Phase 1 FDA Drug

• 1 other identifier: ALXN2050-HV-110
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Healthy

Keywords

ALXN2050; Cyclosporine; Tacrolimus; Mycophenolate Mofetil; Drug-Drug Interaction; Pharmacokinetics; Safety; Factor D Inhibitor

Outcome Measures

Primary Outcomes (14)

• 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 Outcomes (1)

• Parts 1-3: Number of Participants Experiencing Treatment-emergent Adverse Events

  Day 1 through up to 12 days postdose

Study Arms (3)

Part 1 - Cyclosporine

EXPERIMENTAL

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; Drug: Cyclosporine

Part 2 - Tacrolimus

EXPERIMENTAL

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; Drug: Tacrolimus

Part 3 - MMF

EXPERIMENTAL

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; Drug: MMF

Interventions

ALXN2050 DRUG

Oral tablet.

Also known as: ACH-0145228 (formerly)

Part 1 - Cyclosporine; Part 2 - Tacrolimus; Part 3 - MMF

Cyclosporine DRUG

Oral capsule.

Part 1 - Cyclosporine

Tacrolimus DRUG

Oral capsule.

Part 2 - Tacrolimus

MMF DRUG

Oral tablet.

Part 3 - MMF

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (1)

Clinical Study Site

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

rhoA GTP-Binding Protein; Cyclosporine; Tacrolimus

Intervention Hierarchy (Ancestors)

rho GTP-Binding Proteins; Monomeric GTP-Binding Proteins; GTP-Binding Proteins; GTP Phosphohydrolases; Acid Anhydride Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Intracellular Signaling Peptides and Proteins; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This will be a 3-part study with each part being an open-label, fixed-sequence study in healthy adult participants. The 3 parts of the study may be conducted concurrently.

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: January 21, 2022
• Study Start: January 11, 2022
• Primary Completion: March 21, 2022
• Study Completion: March 21, 2022
• Last Updated: April 4, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR

Locations

US (1)