Study of Danicopan in Participants With Hepatic Impairment

A Phase 1, 2-Part, Open-Label, Single-Dose, Parallel Group Study to Determine the Effect of Hepatic Impairment on the Safety, Tolerability, and Pharmacokinetics of ACH-0144471 in Adult Subjects

The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics (PK) of ACH-0144471 (danicopan) in participants with hepatic impairment (HI) as compared to healthy matched participants.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Danicopan

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Clinical Trial Site
    • Orlando, Florida, United States, 32809
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Body mass index range of 18.0 to 40.0 kilograms (kg)/square meter with a minimum body weight of 50 kg at Screening.
• Females must be of non-childbearing potential.
• Males must agree to abstinence or use a highly effective method of contraception.

HI Participants:

• Be sufficiently healthy for study participation.
• Diagnosis of chronic (>6 months) stable hepatic insufficiency.
• A stable medication regimen.
• In good general health at Screening and check-in, allowing for the concurrent illnesses associated with HI.
• Evidence of cirrhosis due to hepatitis C virus (HCV), hepatitis B virus (HBV) infection, cryptogenic, alcohol abuse, or nonalcoholic steatohepatitis.
• No evidence of hepatocellular carcinoma.
• Have HI as assessed by a Child-Pugh classification score at Screening.

Healthy Participants:

• Participants must be demographically matched to a hepatically impaired participant.
• Medically healthy and without a clinically significant medical history.

Key Exclusion Criteria:

• Evidence of any other clinically significant deviation from normal in a clinical laboratory for the match-controlled participants and laboratory findings beyond those that are consistent with the degree of HI from hepatic participants.
• History of any medical or psychiatric condition or disease.
• Any previous procedure that could alter the absorption or excretion of orally administered drugs.
• Body temperature greater than or equal to 38 degrees centigrade on Day -1 or Day 1 prior to dosing; history of febrile illness or other evidence of infection within 14 days prior to dosing.
• History or presence of drug or alcohol abuse within 6 months prior to dosing; current tobacco/nicotine user; positive for alcohol and/or drugs-of-abuse at Screening or check in.
• Participants who have received eculizumab at any dose or interval within the past 75 days.
• Participation in any other investigational study drug trial 30 days before dosing.
• Donation of whole blood from 3 months before dosing or of plasma from 30 days before dosing; receipt of blood products within 6 months before dosing.

HI Participants:

• Any acute or chronic non-hepatic condition that would limit the participant's ability to participate in this study.
• Any other unspecified reason that would make the participant unsuitable for enrollment.
• Any screening laboratory evaluation outside the laboratory reference ranges not related to HI.
• Fluctuating or rapidly deteriorating hepatic function within the screening period and up to 30 days prior to Day 1.
• History of chronic liver disease due to Wilson's disease.
• History of liver or other solid organ transplants.

Healthy Participants:

• Clinical laboratory evaluations outside of the reference range at Screening or check-in.
• Evidence of acute or chronic liver disease.
• Use of any prescription medications/products within 14 days prior to dosing.
• Use of over-the-counter, nonprescription preparations within 7 days prior to dosing.
• Evidence of chronic HBV or chronic HCV infection.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Healthy Match; Single 200-milligram (mg) dose of danicopan on Day 1 in healthy participants (matched control group with normal hepatic function).	Drug: Danicopan; Oral tablet.; Other Names: ALXN2040; ACH-0144471 (formerly); ACH-4471; ACH4471; 4471
Experimental: Part 1: Moderate HI; Single 200-mg dose of danicopan on Day 1 in participants with moderate HI.	Drug: Danicopan; Oral tablet.; Other Names: ALXN2040; ACH-0144471 (formerly); ACH-4471; ACH4471; 4471

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under The Plasma Concentration Versus Time Curve From Time 0 Extrapolated To Infinity (AUC0-inf) Of Danicopan	Up to 72 hours postdose
Area Under The Plasma Concentration Versus Time Curve From Time 0 To The Last Measurable Concentration (AUC0-t) Of Danicopan	Up to 72 hours postdose
Maximum Observed Plasma Concentration (Cmax) Of Danicopan	Up to 72 hours postdose
Time To Maximum Observed Plasma Concentration (Tmax) Of Danicopan	Up to 72 hours postdose

Secondary Outcome Measures

Outcome Measure	Time Frame
Participants Experiencing Treatment-emergent Adverse Events	Day 1 (postdose) through follow-up visit (10 [+/- 2] days after last study drug administration)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Actual): September 21, 2018
• Study Completion (Actual): September 21, 2018

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: June 1, 2018
• First Posted (Actual): June 13, 2018

Study Record Updates

• Last Update Posted (Actual): August 20, 2021
• Last Update Submitted That Met QC Criteria: August 16, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Hepatic Impairment; Danicopan; ALXN2040; ACH-0144471; Factor D Inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: ACH471-012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No