Study of Danicopan in Participants With Hepatic Impairment

NCT03555539 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ACH471-012
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Hepatic Impairment

Keywords

Hepatic Impairment; Danicopan; ALXN2040; ACH-0144471; Pharmacokinetics; Factor D Inhibitor; Safety

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• Participants Experiencing Treatment-emergent Adverse Events

  Day 1 (postdose) through follow-up visit (10 [+/- 2] days after last study drug administration)

Study Arms (2)

Part 1: Healthy Match

EXPERIMENTAL

Single 200-milligram (mg) dose of danicopan on Day 1 in healthy participants (matched control group with normal hepatic function).

Drug: Danicopan

Part 1: Moderate HI

EXPERIMENTAL

Single 200-mg dose of danicopan on Day 1 in participants with moderate HI.

Drug: Danicopan

Interventions

Danicopan DRUG

Oral tablet.

Also known as: ALXN2040, ACH-0144471 (formerly), ACH-4471, ACH4471, 4471

Part 1: Healthy Match; Part 1: Moderate HI

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (2)

Clinical Trial Site

Miami, Florida, 33136, United States

Location

Clinical Trial Site

Orlando, Florida, 32809, United States

Location

MeSH Terms

Interventions

danicopan; rhoA GTP-Binding Protein

Intervention Hierarchy (Ancestors)

rho GTP-Binding Proteins; Monomeric GTP-Binding Proteins; GTP-Binding Proteins; GTP Phosphohydrolases; Acid Anhydride Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Intracellular Signaling Peptides and Proteins

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: June 1, 2018
• First Posted: June 13, 2018
• Study Start: May 1, 2018
• Primary Completion: September 21, 2018
• Study Completion: September 21, 2018
• Last Updated: August 20, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share

Locations

US (2)