Study of a Single Dose of Danicopan in Healthy Participants

NCT04889677 | Completed Phase 1

• 1 other identifier: ACH471-001
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Danicopan; ALXN2040; ACH-0144471; Factor D Inhibitor; Pharmacokinetics; Pharmacodynamics; Ascending Dose

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (5)

Group 1: 200 mg

EXPERIMENTAL

All participants (fasted) received either 200 mg of danicopan as a single oral dose or dose-matched placebo.

Drug: Danicopan; Drug: Placebo

Group 2: 600 mg

EXPERIMENTAL

All participants (fasted) received either 600 mg of danicopan as a single oral dose or dose-matched placebo.

Drug: Danicopan; Drug: Placebo

Group 3: 1200 mg

EXPERIMENTAL

All participants (fasted) received either 1200 mg of danicopan as a single oral dose or dose-matched placebo.

Drug: Danicopan; Drug: Placebo

Group 4: 2400 mg

EXPERIMENTAL

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: Danicopan; Drug: Placebo

Group 5: 1200 mg

EXPERIMENTAL

All participants (fed) received either 1200 mg of danicopan as a single oral dose or dose-matched placebo.

Drug: Danicopan; Drug: Placebo

Interventions

Danicopan DRUG

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

Group 1: 200 mg; Group 2: 600 mg; Group 3: 1200 mg; Group 4: 2400 mg; Group 5: 1200 mg

Placebo DRUG

Group 1: 200 mg; Group 2: 600 mg; Group 3: 1200 mg; Group 4: 2400 mg; Group 5: 1200 mg

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Clinical Trial Site

Auckland, New Zealand

Location

Related Publications (1)

• 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.

  PMID: 31573880 RESULT

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: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2021
• First Posted: May 17, 2021
• Study Start: February 4, 2016
• Primary Completion: June 21, 2016
• Study Completion: June 21, 2016
• Last Updated: May 17, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1)