A Drug Interaction Study of ACH-0145228

NCT04709081 | Completed Phase 1 FDA Drug

• 2 other identifiers: ACH228-003CA28776
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Factor D Inhibitor; Complement; Capsule; Pharmacokinetics; Drug Interaction

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (3)

• 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)

Study Arms (2)

Part 1: ACH-0145228, Midazolam, and Digoxin

EXPERIMENTAL

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; Drug: Midazolam; Drug: Digoxin

Part 2: ACH-0145228 and Itraconazole

EXPERIMENTAL

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; Drug: Itraconazole

Interventions

ACH-0145228 DRUG

ACH-0145228 was dosed as 2 x 60 milligram (mg) (Part 1) or 1 x 40 mg (Part 2) powder in capsules.

Also known as: ALXN2050

Part 1: ACH-0145228, Midazolam, and Digoxin; Part 2: ACH-0145228 and Itraconazole

Midazolam DRUG

Midazolam was dosed at 2 mg (1 milliliter \[mL\] of a 2 mg/mL syrup).

Also known as: Midazolam HCl

Part 1: ACH-0145228, Midazolam, and Digoxin

Digoxin DRUG

Digoxin was dosed as Lanoxin (or generic equivalent) at 1 x 0.25 mg tablet.

Also known as: Lanoxin

Part 1: ACH-0145228, Midazolam, and Digoxin

Itraconazole DRUG

Itraconazole was dosed as Sporanox (or generic equivalent) at 200 mg (20 mL of a 10 mg/mL oral solution).

Also known as: Sporanox

Part 2: ACH-0145228 and Itraconazole

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead
• Achillion, a wholly owned subsidiary of Alexion: collaborator
• Celerion: collaborator

Study Sites (1)

Clinical Study Site

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

Midazolam; Digoxin; Itraconazole

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Piperazines

Study Design

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

Model Details: Part 1 and Part 2 could be conducted concurrently or separately.

Study Record Dates

• First Submitted: January 12, 2021
• First Posted: January 14, 2021
• Study Start: December 22, 2019
• Primary Completion: April 16, 2020
• Study Completion: April 16, 2020
• Last Updated: January 14, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)