Study of a Single Dose of Danicopan in Healthy Participants

A Single Ascending Dose Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of ACH 0144471 In Healthy Volunteers

This was a single ascending dose, randomized, double-blind study assessing the safety, tolerability, pharmacokinetics, and pharmacodynamics of danicopan in healthy participants. Four different doses (200 milligrams [mg], 600 mg, 1200 mg, 2400 mg) and dose-matched placebo were administered under fasted and fed conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Danicopan

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy defined as having no clinically relevant abnormalities identified by a detailed medical history, physical examination, blood pressure and pulse rate measurements, 12-lead electrocardiogram, and clinical laboratory tests.
• Body mass index of 18 to 30 kilograms (kg)/meter squared with a minimum body weight of 50 kg.

Exclusion Criteria:

• History or clinically relevant evidence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
• Any condition possibly affecting drug absorption (for example, gastrectomy), cholecystectomy to be considered acceptable.
• Body temperature ≥ 38°Celcius on Day -1 or Day 1 Hour 0; history of febrile illness or other evidence of infection within 14 days prior to study drug administration.
• Current tobacco/nicotine users; consumption of any alcohol within 72 hours before study drug administration or a history of regular alcohol consumption exceeding 21 drinks/week within 6 months of Screening; positive urine drug screen at Screening or Day -1.
• Clinically significant laboratory abnormalities at either Screening or Day -1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1: 200 mg; All participants (fasted) received either 200 mg of danicopan as a single oral dose or dose-matched placebo.	Drug: Placebo; Drug: Danicopan; Other Names: ALXN2040; ACH-0144471 (formerly); ACH-4471; ACH4471; 4471
EXPERIMENTAL: Group 2: 600 mg; All participants (fasted) received either 600 mg of danicopan as a single oral dose or dose-matched placebo.	Drug: Placebo; Drug: Danicopan; Other Names: ALXN2040; ACH-0144471 (formerly); ACH-4471; ACH4471; 4471
EXPERIMENTAL: Group 3: 1200 mg; All participants (fasted) received either 1200 mg of danicopan as a single oral dose or dose-matched placebo.	Drug: Placebo; Drug: Danicopan; Other Names: ALXN2040; ACH-0144471 (formerly); ACH-4471; ACH4471; 4471
EXPERIMENTAL: Group 4: 2400 mg; All participants (fasted) received either 2400 mg of danicopan administered as 2 single doses of 1200 mg each, 12 hours apart, or dose-matched placebo.	Drug: Placebo; Drug: Danicopan; Other Names: ALXN2040; ACH-0144471 (formerly); ACH-4471; ACH4471; 4471
EXPERIMENTAL: Group 5: 1200 mg; All participants (fed) received either 1200 mg of danicopan as a single oral dose or dose-matched placebo.	Drug: Placebo; Drug: Danicopan; Other Names: ALXN2040; ACH-0144471 (formerly); ACH-4471; ACH4471; 4471

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence Of Serious Adverse Events, Grade 3 Or 4 Adverse Events (AEs), AEs Leading To Discontinuation, And Clinically Significant Laboratory Abnormalities And Electrocardiogram Abnormalities	Day 1 through Day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under The Plasma Concentration-time Curve Extrapolated To Infinity (AUC0-inf) Of Danicopan Under Both Fed And Fasted Conditions	Up to 144 hours postdose
Maximal Plasma Concentration (Cmax) Of Danicopan Under Both Fed And Fasted Conditions	Up to 144 hours postdose
Time To Reach The Maximal Plasma Concentration (Tmax) Of Danicopan Under Both Fed And Fasted Conditions	Up to 144 hours postdose
Relationship Between Alternative Pathway Inhibition And Danicopan Plasma Concentrations	Up to 144 hours postdose

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Wiles JA, Galvan MD, Podos SD, Geffner M, Huang M. Discovery and Development of the Oral Complement Factor D Inhibitor Danicopan (ACH-4471). Curr Med Chem. 2020;27(25):4165-4180. doi: 10.2174/0929867326666191001130342.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 4, 2016
• Primary Completion (ACTUAL): June 21, 2016
• Study Completion (ACTUAL): June 21, 2016

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: Pharmacokinetics; Pharmacodynamics; Danicopan; ALXN2040; ACH-0144471; Factor D Inhibitor; Ascending Dose
• Other Study ID Numbers: ACH471-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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