Study of Radiolabeled Danicopan in Healthy Male Participants

A Phase I, Open-Label, Single Dose ADME Study of 14C-ACH-0144471 in Healthy Male Subjects

This was an open-label study to evaluate the absorption, distribution, metabolism, and excretion of radioactivity in healthy male participants following a single 150-milligram (mg) oral dose of carbon-14 ([14C])-ACH-014447 ([14C])-danicopan) containing approximately 100 microcuries (µCi) of [14C].

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: [14C]-Danicopan

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Key Inclusion Criteria:

• Healthy was defined as having no clinical relevant abnormalities identified by a detailed medical history, physical exam, blood pressure and pulse rate measurements, 12-lead electrocardiogram, and clinical laboratory tests.
• Body mass index of ≥ 18 and ≤ 30 kilograms (kg)/meter squared and weight of ≥ 50 kg and ≤ 100 kg.
• Regular daily bowel movements (that is, production of at least 1 stool per day).
• Non-smoker or ex-smoker who had not used tobacco or nicotine products for ≥ 3 months prior to screening.

Key Exclusion Criteria:

• History or clinically relevant evidence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
• History of conditions or procedures possibly affecting drug absorption or excretion. A history of appendectomy, cholecystectomy, and hernia repair was allowed if they were not associated with complications.
• Active bacterial infection or clinically significant active viral infection, a body temperature > 38°Celcius, or other evidence of infection on Day 1, or with a history of febrile illness within 7 days prior to Day 1.
• Healthy participants who had been exposed to significant radiation levels of > 5 millisieverts in the last year prior to screening.
• Clinically significant laboratory abnormalities at screening or Day -1, as well as absolute neutrophil counts, platelets, and hemoglobin outside of reference ranges.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [14C]-Danicopan; Participants were administered a single oral dose of danicopan between 151 and 154 mg (nominal dose of 150 mg), providing approximately 100 μCi of [14C] radiolabel in the form of [14C]-danicopan.	Drug: [14C]-Danicopan; Liquid-filled capsules.; Other Names: ALXN2040; ACH-4471; ACH4471; 4471; ACH-014447

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean Cumulative Percentages Of Total Radioactivity Recovered In Urine And Feces Following A Single Oral Dose Of [14C]-Danicopan	Up to 96 hours postdose or maximum of 216 hours postdose for extended collection period
Whole Blood And Plasma Pharmacokinetics (PK) Of Total Radioactivity After A Single Oral Dose Of [14C]-Danicopan: Area Under The Concentration-time Curve From Time 0 To The Time Of Last Quantifiable Concentration (AUC0-t)	Up to 96 hours postdose or maximum of 216 hours postdose for extended collection period
Whole Blood And Plasma PK Of Total Radioactivity After A Single Oral Dose Of [14C]-Danicopan: Area Under The Concentration-time Curve Extrapolated to Infinity (AUC0-inf)	Up to 96 hours postdose or maximum of 216 hours postdose for extended collection period
Whole Blood And Plasma PK Of Total Radioactivity After A Single Oral Dose Of [14C]-Danicopan: Maximum Observed Concentration (Cmax)	Up to 96 hours postdose or maximum of 216 hours postdose for extended collection period
Whole Blood And Plasma PK Of Total Radioactivity After A Single Oral Dose Of [14C]-Danicopan: Time To Maximum Observed Concentration (Tmax)	Up to 96 hours postdose or maximum of 216 hours postdose for extended collection period
Plasma PK Of Danicopan After A Single Oral Dose Of [14C]-Danicopan: AUC0-t	Up to 96 hours postdose
Plasma PK Of Danicopan After A Single Oral Dose Of [14C]-Danicopan: AUC0-inf	Up to 96 hours postdose
Plasma PK Of Danicopan After A Single Oral Dose Of [14C]-Danicopan: Cmax	Up to 96 hours postdose
Plasma PK Of Danicopan After A Single Oral Dose Of [14C]-Danicopan: Tmax	Up to 96 hours postdose
[14C]-Danicopan Metabolites In Plasma, Urine, And Feces	Up to 96 hours postdose or maximum of 216 hours postdose for extended collection period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Of Total Radioactivity Detected For Each [14C]-Danicopan Metabolite in Plasma, Urine, And Feces	[14C]-Danicopan metabolic profiling in plasma, urine, and feces was performed in samples containing sufficient amounts of radioactivity. The percent of dose represented by each of the metabolites was calculated using the radioactivity concentration equivalent data combined with the metabolic profiling data. The percentage of each identified metabolite to total radioactivity in plasma was estimated based on plasma metabolic profiling data.	Up to 96 hours postdose or maximum of 216 hours postdose for extended collection period
Incidence Of Treatment-emergent Adverse Events		Day 1 through Day 10

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2017
• Primary Completion (Actual): October 15, 2017
• Study Completion (Actual): October 15, 2017

Study Registration Dates

• First Submitted: May 12, 2021
• First Submitted That Met QC Criteria: May 12, 2021
• First Posted (Actual): May 17, 2021

Study Record Updates

• Last Update Posted (Actual): May 17, 2021
• Last Update Submitted That Met QC Criteria: May 12, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Distribution; Absorption; Danicopan; ALXN2040; ACH-0144471; Metabolism; Excretion; Total Radioactivity; ADME
• Other Study ID Numbers: ACH471-005

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