Study of ALXN2050 in Healthy Adult Participants of Japanese Descent

Study Overview
=================
Brief Summary
-----------------
This is a Phase 1 bridging study being conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ALXN2050 after both single- and multiple-dosing in healthy participants of Japanese descent.

Official Title
-----------------
A Phase 1 Study to Determine the Safety, Tolerability, and Pharmacokinetics of ALXN2050 in Healthy Participants of Japanese Descent

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: ALXN2050
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key 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. Participants must be of Japanese descent defined as: First generation (born to 2 Japanese parents and 4 Japanese grandparents); Born in Japan, and not have lived outside Japan for greater than 5 years; Lifestyle, including diet, must not have significantly changed since leaving Japan. Participants must be able to speak, read, and understand the Japanese and English languages. Body mass index within the range 18.5 to 30.0 kilograms (kg)/meter squared, inclusive, with a minimum body weight of 50.0 kg at Screening. Key Exclusion Criteria: History of any medical or psychiatric condition or disease that, in the opinion of the Investigator or designee, 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. History of significant multiple and/or severe allergies. Any previous procedure that could alter absorption or excretion of orally administered drugs. 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. Body temperature ≥ 38.0°Celcius, at Screening or prior to the first dose of study intervention. 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/nicotine 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: ALXN2050 (Dose 1)<br>Participants will receive ALXN2050 (Dose 1) as follows under fasting conditions: 120-milligrams (mg) single dose, 3-day washout, then 120-mg twice daily (BID) dosing. | Drug: ALXN2050<br>* Oral tablet.<br>* Other names: ACH-0145228 (formerly);|
| Experimental: Cohort 1: Placebo (Dose 1)<br>Participants will receive placebo (Dose 1) as follows under fasting conditions: 120-mg placebo single dose, 3-day washout, then 120-mg placebo BID dosing. | Drug: Placebo<br>* Oral tablet.<br>|
| Experimental: Cohort 2: ALXN2050 (Dose 2)<br>Participants will receive ALXN2050 (Dose 2) as follows under fasting conditions: 180-mg single dose, 3-day washout, then 180-mg BID dosing. | Drug: ALXN2050<br>* Oral tablet.<br>* Other names: ACH-0145228 (formerly);|
| Experimental: Cohort 2: Placebo (Dose 2)<br>Participants will receive placebo (Dose 2) as follows under fasting conditions: 180-mg placebo single dose, 3-day washout, then 180-mg placebo BID dosing. | Drug: Placebo<br>* Oral tablet.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Of Participants With Treatment-emergent Adverse Events | see Time Frame - defined | Day 1 (after first dose) through follow-up (7 +/- 2 days after final dose) | 
| Area Under The Concentration-time Curve From Time Zero To Infinity (AUCinf) For Single-dose ALXN2050 | see Time Frame - defined | Up to 72 hours postdose | 
| Maximum Plasma Concentration (Cmax) For Single-dose ALXN2050 | see Time Frame - defined | Up to 72 hours postdose | 
| Time To Maximum Plasma Concentration (Tmax) For Single-dose ALXN2050 | see Time Frame - defined | Up to 72 hours postdose | 
| Area Under The Concentration-time Curve From Time Zero To The 12-hour Time Point (AUC0-12) For Multiple-dose ALXN2050 | see Time Frame - defined | Up to 72 hours postdose | 
| Cmax For Multiple-dose ALXN2050 | see Time Frame - defined | Up to 72 hours postdose | 
| Tmax For Multiple-dose ALXN2050 | see Time Frame - defined | Up to 72 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alternative Pathway Activity As Measured By Wieslab Assay | see Time Frame - defined | Up to 72 hours postdose | 
| Complement Factor B Fraction b Levels | see Time Frame - defined | Up to 72 hours postdose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ALXN2050, Pharmacokinetics, Pharmacodynamics, Japanese Descent