A Drug Interaction Study of ACH-0145228

Sponsor

Alexion Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT04709081

Collaborator

Achillion, a wholly owned subsidiary of Alexion (Industry), Celerion (Industry)

Enrollment

Location

Arms

3.8

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: ACH-0145228 Drug: Midazolam Drug: Digoxin Drug: Itraconazole	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

38 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Part 1 and Part 2 could be conducted concurrently or separately.Part 1 and Part 2 could be conducted concurrently or separately.

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Dec 22, 2019

Actual Primary Completion Date :

Apr 16, 2020

Actual Study Completion Date :

Apr 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: ACH-0145228, Midazolam, and Digoxin 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 ACH-0145228 was dosed as 2 x 60 milligram (mg) (Part 1) or 1 x 40 mg (Part 2) powder in capsules. Other Names: ALXN2050 Drug: Midazolam Midazolam was dosed at 2 mg (1 milliliter [mL] of a 2 mg/mL syrup). Other Names: Midazolam HCl Drug: Digoxin Digoxin was dosed as Lanoxin (or generic equivalent) at 1 x 0.25 mg tablet. Other Names: Lanoxin
Experimental: Part 2: ACH-0145228 and Itraconazole 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 ACH-0145228 was dosed as 2 x 60 milligram (mg) (Part 1) or 1 x 40 mg (Part 2) powder in capsules. Other Names: ALXN2050 Drug: Itraconazole Itraconazole was dosed as Sporanox (or generic equivalent) at 200 mg (20 mL of a 10 mg/mL oral solution). Other Names: Sporanox

Arm

Intervention/Treatment

Experimental: Part 1: ACH-0145228, Midazolam, and Digoxin

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

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

Other Names:

ALXN2050

Drug: Midazolam

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

Other Names:

Midazolam HCl

Drug: Digoxin

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

Other Names:

Lanoxin

Experimental: Part 2: ACH-0145228 and Itraconazole

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

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

Other Names:

ALXN2050

Drug: Itraconazole

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

Other Names:

Sporanox

Outcome Measures

Primary Outcome Measures

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

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.