A Drug Interaction Study of ACH-0145228

Alexion Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Itraconazole; Drug: ACH-0145228; Drug: Digoxin; Drug: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT04709081

CA28776 (Other Identifier)

ACH228-003

Details and patient eligibility

About

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.

Enrollment: 38 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. 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.
2. No clinically significant history or presence of electrocardiogram abnormalities at screening and prior to first dosing in Period 1.
3. Non-sterile male participants must agree to abstinence or use a highly effective method of contraception.
4. Female participants must be of non-childbearing potential and need not employ a method of contraception.

Exclusion criteria

1. Clinically significant laboratory abnormalities.
2. 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.
3. 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.
4. History or presence of clinically significant seizures, head injury, or head trauma.
5. History of procedures that could alter absorption or excretion of orally administered drugs.
6. A history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs.
7. Body temperature ≥ 38.0°Celsius at screening or prior to first dosing in Period 1.
8. 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.
9. 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.
10. History or presence of any risk factors for Torsades de Pointes.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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38 participants in 2 patient groups

Part 1: ACH-0145228, Midazolam, and Digoxin

Experimental group

Description:

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.

Treatment:

Drug: Midazolam

Drug: Digoxin

Drug: ACH-0145228

Part 2: ACH-0145228 and Itraconazole

Experimental group

Description:

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.

Treatment:

Drug: ACH-0145228

Drug: Itraconazole