A Drug Interaction Study of ACH-0145228

Study Overview
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Brief Summary
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This was a 2-part study (Part 1 and Part 2), with each part being an open-label, fixed sequence, 2-period study in healthy adult participants.

Official Title
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A Two-Part Phase 1 Study to Evaluate the Potential Drug Interaction Between ACH-0145228 and Midazolam, Digoxin, and Itraconazole in Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: ACH-0145228
* Drug: Midazolam
* Drug: Digoxin
* Drug: Itraconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index in the range of 18.0 to 32.0 kilograms (kg)/meter squared, inclusive, with a minimum body weight of 50.0 kg at screening. No clinically significant history or presence of electrocardiogram abnormalities at screening and prior to first dosing in Period 1. Non-sterile male participants must agree to abstinence or use a highly effective method of contraception. Female participants must be of non-childbearing potential and need not employ a method of contraception. Exclusion Criteria: Clinically significant laboratory abnormalities. 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. History or presence of drug or alcohol abuse within previous 2 years, current tobacco/nicotine user, or positive for alcohol and/or drug screen at screening or Day -1 of Period 1. History or presence of clinically significant seizures, head injury, or head trauma. History of procedures that could alter absorption or excretion of orally administered drugs. A history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs. Body temperature ≥ 38.0°Celsius at screening or prior to first dosing in Period 1. Donation of whole blood from 3 months prior to first dosing, or of plasma from 30 days before first dosing, or receipt of blood products within 6 months prior to first dosing. Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives (if known) or 30 days before first dosing, whichever is longer. History or presence of any risk factors for Torsades de Pointes.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part 1 and Part 2 could be conducted concurrently or separately.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: ACH-0145228, Midazolam, and Digoxin<br>Period 1: Participants received single doses of midazolam and digoxin. Period 2: Participants received ACH-0145228 twice daily, in addition to coadministration with single doses of midazolam and digoxin. Scheduled pharmacokinetics (PK) blood and urine samples were collected, with a washout period of at least 7 days between collection of the last PK blood sample in Period 1 and the first dose of ACH-0145228 in Period 2. | Drug: ACH-0145228<br>* ACH-0145228 was dosed as 2 x 60 milligram (mg) (Part 1) or 1 x 40 mg (Part 2) powder in capsules.<br>* Other names: ALXN2050;Drug: Midazolam<br>* Midazolam was dosed at 2 mg (1 milliliter [mL] of a 2 mg/mL syrup).<br>* Other names: Midazolam HCl;Drug: Digoxin<br>* Digoxin was dosed as Lanoxin (or generic equivalent) at 1 x 0.25 mg tablet.<br>* Other names: Lanoxin;|
| Experimental: Part 2: ACH-0145228 and Itraconazole<br>Period 1: Participants received a single dose of ACH-0145228. Period 2: Participants received itraconazole once daily, in addition to coadministration with a single dose of ACH-0145228. Scheduled PK blood samples were collected, with a washout period of at least 2 days between collection of the last PK blood sample in Period 1 and the first dose of itraconazole in Period 2. | Drug: ACH-0145228<br>* ACH-0145228 was dosed as 2 x 60 milligram (mg) (Part 1) or 1 x 40 mg (Part 2) powder in capsules.<br>* Other names: ALXN2050;Drug: Itraconazole<br>* Itraconazole was dosed as Sporanox (or generic equivalent) at 200 mg (20 mL of a 10 mg/mL oral solution).<br>* Other names: Sporanox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Area Under The Concentration Versus Time Curve From Time 0 Extrapolated To Infinity (AUC0-inf) Of Single-dose Midazolam Under Multiple Doses Of ACH-0145228 |  | Up to 24 hours postdose | 
| Part 1: Maximum Observed Concentration (Cmax) Of Single-dose Midazolam Under Multiple Doses Of ACH-0145228 |  | Up to 24 hours postdose | 
| Part 1: Time To Maximum Observed Concentration (Tmax) Of Single-dose Midazolam Under Multiple Doses Of ACH-0145228 |  | Up to 24 hours postdose | 
| Part 1: AUC0-inf Of Single-dose Digoxin Under Multiple Doses Of ACH-0145228 |  | Up to 168 hours postdose | 
| Part 1: Cmax Of Single-dose Digoxin Under Multiple Doses Of ACH-0145228 |  | Up to 168 hours postdose | 
| Part 1: Tmax Of Single-dose Digoxin Under Multiple Doses Of ACH-0145228 |  | Up to 168 hours postdose | 
| Part 2: AUC0-inf Of Single-dose ACH-0145228 Under Multiple Doses Of Itraconazole |  | Up to 96 hours postdose | 
| Part 2: Cmax Of Single-dose ACH-0145228 Under Multiple Doses Of Itraconazole |  | Up to 96 hours postdose | 
| Part 2: Tmax Of Single-dose ACH-0145228 Under Multiple Doses Of Itraconazole |  | Up to 96 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number Of Participants With Treatment-emergent Adverse Events (TEAEs) After Multiple Doses Of ACH-0145228 Coadministered With A Single Dose Of Midazolam |  | Day 1 (postdose) through follow-up (14 [+/- 2] days after last study drug administration) | 
| Part 1: Number Of Participants With TEAEs After Multiple Doses Of ACH-0145228 Coadministered With A Single Dose Of Digoxin |  | Day 1 (postdose) through follow-up (14 [+/- 2] days after last study drug administration) | 
| Part 2: Number Of Participants With TEAEs After A Single Dose Of ACH-0145228 Coadministered With Multiple Doses Of Itraconazole |  | Day 1 (postdose) through follow-up (14 [+/- 2] days after last study drug administration) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Factor D Inhibitor, Complement, Capsule, Pharmacokinetics, Drug Interaction