Study of Danicopan in Participants With Hepatic Impairment

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: Danicopan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study was to be conducted sequentially in 2 parts. Part 1: Participants with moderate HI (based on Child-Pugh scores) were compared to demographically matched participants with normal hepatic function. Following a review of PK and safety data from Part 1, a decision was to be made by the principle investigators and the sponsor whether to conduct Part 2 of this study, which was planned to enroll participants with severe and mild HI.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Healthy Match<br>Single 200-milligram (mg) dose of danicopan on Day 1 in healthy participants (matched control group with normal hepatic function). | Drug: Danicopan<br>* Oral tablet.<br>* Other names: 4471;|
| Experimental: Part 1: Moderate HI<br>Single 200-mg dose of danicopan on Day 1 in participants with moderate HI. | Drug: Danicopan<br>* Oral tablet.<br>* Other names: 4471;|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic Impairment, Danicopan, ALXN2040, ACH-0144471, Pharmacokinetics, Factor D Inhibitor, Safety