A Drug Interaction Study of ACH-0145228

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ACH-0145228; Drug: Midazolam; Drug: Digoxin; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Clinical Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals
• Collaborators: Celerion; Achillion, a wholly owned subsidiary of Alexion

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2019
• Primary Completion (Actual): April 16, 2020
• Study Completion (Actual): April 16, 2020

Study Registration Dates

• First Submitted: January 12, 2021
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 14, 2021

Study Record Updates

• Last Update Posted (Actual): January 14, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Complement; Capsule; Factor D Inhibitor; Drug Interaction
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Anti-Infective Agents; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Cardiotonic Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Digoxin; Midazolam; Itraconazole
• Other Study ID Numbers: ACH228-003; CA28776 (Other Identifier: Celerion)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No