Study of Danicopan in Participants With Normal Kidney Function and Participants With Kidney Dysfunction

NCT04935294 | Completed Phase 1 FDA Drug

• 1 other identifier: ACH471-009
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 4

Brief Summary

This was an open-label, nonrandomized, multi-center, single-dose, parallel group study to evaluate the effect of severe renal impairment (RI) on the safety, tolerability, pharmacokinetics, and pharmacodynamics of danicopan (ACH-0144471) compared to demographically-matched healthy participants with normal renal function.

Conditions

Healthy; Renal Dysfunction

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Participants With Treatment-emergent Adverse Events

  Day 1 through Day 10 (+/- 2 days)

Secondary Outcomes (6)

• Area Under The Plasma Concentration-time Curve Extrapolated To Infinity (AUC0-inf) Of Danicopan

  Up to 72 hours postdose

• Maximum Observed Plasma Concentration (Cmax) Of Danicopan

  Up to 72 hours postdose

• Time To Reach The Maximum Observed Plasma Concentration (Tmax) Of Danicopan

  Up to 72 hours postdose

• Alternative Pathway Activity As Measured By Wieslab Assay

  Up to 72 hours postdose

• Change From Baseline In Plasma Bb Fragment Of Complement Factor B Concentration

  Baseline, Up to 72 hours postdose

Study Arms (2)

Group 1: Matched Control Group Of Healthy Participants

EXPERIMENTAL

Participants received a single 200-milligram (mg) treatment on Day 1.

Drug: Danicopan

Group 2: Severe RI And Not On Dialysis

EXPERIMENTAL

Participants received a single 200-mg treatment on Day 1.

Drug: Danicopan

Interventions

Danicopan DRUG

Oral tablet.

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

Group 1: Matched Control Group Of Healthy Participants; Group 2: Severe RI And Not On Dialysis

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 (BMI) in the range of 18.0 to 40.0 kilograms (kg)/meter squared, inclusive, with a minimum body weight of 50 kg at screening.
• Stable creatinine clearance.
• Participants with RI must have met the following additional criteria to be enrolled in this study
• A stable medication regimen was required. Concomitant medications must have been approved by the Sponsor and Investigator (or designee) or pre-specified in the protocol.
• Abnormal laboratory values must not have been clinically relevant at screening or check-in.
• Participants were in good general health at screening and check-in, allowing for the concurrent illnesses associated with chronic kidney disease.
• Stable severe RI.
• Healthy matched control participants with normal renal function must have met the following additional criteria to be enrolled in this study
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram, and vital sign measurements at screening or check-in, as determined by the Investigator (or designee).
• Participants had normal renal function.
• Participants must have been demographically matched to a renally impaired participant by age (± 10 years), sex, and BMI (± 20%) at screening.

You may not qualify if:

• History of any medical or psychiatric condition or disease (aside from RI for RI participants) that might have limited 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 of procedures that could alter absorption or excretion of orally administered drugs.
• Body temperature ≥ 38°Celsius on Day - 1 or Day 1 predose; history of febrile illness, or other evidence of infection, within 14 days prior to study drug administration.
• History or presence of drug or alcohol abuse within previous year; current tobacco/nicotine user; positive for alcohol and/or drug screen at screening.
• 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 prior to check-in, whichever was longer.
• For matched control participants, use of any prescription medications/products within 14 days prior to check-in and use of any over-the-counter, nonprescription preparations within 7 days prior to check-in, unless deemed acceptable by the Investigator (or designee).
• Donation of whole blood from 3 months prior to study drug administration, or of plasma from 30 days prior to study drug administration; receipt of blood products within 6 months prior to check-in.
• Participant required dialysis within the last 3 months prior to check-in.
• Participant did not produce sufficient urine output to permit urine sampling at screening and/or check-in; history of urinary incontinence prior to check-in.
• History of kidney transplant or actively on a transplant waiting list prior to check-in.
• Any acute or chronic non-renal condition prior to check-in that would have limited the participant's ability to complete or participate in this clinical study.
• Any major surgery within 4 weeks of study drug administration.

Sponsors & Collaborators

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

Study Sites (4)

Clinical Trial Site

Miami, Florida, 33014, United States

Location

Clinical Trial Site

Orlando, Florida, 32809, United States

Location

Clinical Trial Site

Minneapolis, Minnesota, 55404, United States

Location

Clinical Trial Site

Saint Paul, Minnesota, 55114, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

danicopan; rhoA GTP-Binding Protein

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

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

Study Record Dates

• First Submitted: June 21, 2021
• First Posted: June 23, 2021
• Study Start: January 24, 2018
• Primary Completion: May 29, 2018
• Study Completion: May 29, 2018
• Last Updated: June 23, 2021

Record last verified: 2021-06

Locations

US (4)