Study of the Metabolism of Danicopan in Healthy Adults

NCT04609696 | Completed Phase 1 FDA Drug

• 1 other identifier: ALXN2040-HV-119
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 2-part open-label, randomized, single-dose, 3-sequence, 3-period crossover, relative bioavailability, and food-effect study comparing different formulations of danicopan in healthy adult participants.

Conditions

Healthy

Keywords

Tablet; Capsule; Danicopan; Bioavailability; Factor D Inhibitor; Food Effect

Outcome Measures

Primary Outcomes (10)

• Relative Bioavailability Of Danicopan Prototype PIC 1 Formulation And Tablet Formulation

  The relative bioavailability of the PIC 1 formulation versus the tablet formulation will be measured by the ratio of select pharmacokinetic (PK) parameters: maximum observed plasma concentration (Cmax), area under the concentration-time curve from time of administration to the last measurable concentration (AUC0-t), and area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf).

  Up to 72 hours postdose

• AUC0-inf Of Danicopan Prototype PIC 1 Formulation Under Both Fed And Fasted Conditions

  Up to 72 hours postdose

• AUC0-t Of Danicopan Prototype PIC 1 Formulation Under Both Fed And Fasted Conditions

  Up to 72 hours postdose

• Cmax Of Danicopan Prototype PIC 1 Formulation Under Both Fed And Fasted Conditions

  Up to 72 hours postdose

• Time to maximum observed plasma concentration (Tmax) Of Danicopan Prototype PIC 1 Formulation Under Both Fed And Fasted Conditions

  Up to 72 hours postdose

• Relative Bioavailability Of Danicopan Prototype PIC 2 Formulation And Tablet Formulation

  The relative bioavailability of the PIC 2 formulation versus the tablet formulation will be measured by the ratio of select PK parameters: Cmax, AUC0-t, and AUC0-inf.

  Up to 72 hours postdose

• AUC0-inf Of Danicopan Prototype PIC 2 Formulation Under Both Fed And Fasted Conditions

  Up to 72 hours postdose

• AUC0-t Of Danicopan Prototype PIC 2 Formulation Under Both Fed And Fasted Conditions

  Up to 72 hours postdose

• Cmax Of Danicopan Prototype PIC 2 Formulation Under Both Fed And Fasted Conditions

  Up to 72 hours postdose

• Tmax Of Danicopan Prototype PIC 2 Formulation Under Both Fed And Fasted Conditions

  Up to 72 hours postdose

Secondary Outcomes (4)

• Number Of Participants Receiving Prototype PIC 1 And Tablet With Treatment-emergent Adverse Events Under Fed Conditions

  Day 1 (postdose) through follow-up (10 [+/- 2] days dosing on Day 1)

• Number Of Participants Receiving Prototype PIC 1 With Treatment-emergent Adverse Events Under Fasted Conditions

  Day 1 (postdose) through follow-up (10 [+/- 2] days dosing on Day 1)

• Number Of Participants Receiving Prototype PIC 2 And Tablet With Treatment-emergent Adverse Events Under Fed Conditions

  Day 1 (postdose) through follow-up (10 [+/- 2] days dosing on Day 1)

• Number Of Participants Receiving Prototype PIC 2 With Treatment-emergent Adverse Events Under Fasted Conditions

  Day 1 (postdose) through follow-up (10 [+/- 2] days dosing on Day 1)

Study Arms (6)

Part 1: Sequence 1

EXPERIMENTAL

Participants will receive danicopan once each period as a single oral dose under fasted or fed conditions as follows: Period 1: Danicopan as the PIC 1 formulation under fed conditions. Period 2: Danicopan as the PIC 1 formulation under fasted conditions. Period 3: Danicopan as a tablet under fed conditions. There will be a washout period of at least 5 days between each danicopan dosing.

Drug: Danicopan: Powder-In-Capsule 1; Drug: Danicopan: Tablet

Part 1: Sequence 2

EXPERIMENTAL

Participants will receive danicopan once each period as a single oral dose under fasted or fed conditions as follows: Period 1: Danicopan as the PIC 1 formulation under fasted conditions. Period 2: Danicopan as a tablet under fed conditions. Period 3: Danicopan as the PIC 1 formulation under fed conditions. There will be a washout period of at least 5 days between each danicopan dosing.

Drug: Danicopan: Powder-In-Capsule 1; Drug: Danicopan: Tablet

Part 1: Sequence 3

EXPERIMENTAL

Participants will receive danicopan once each period as a single oral dose under fasted or fed conditions as follows: Period 1: Danicopan as a tablet under fed conditions. Period 2: Danicopan as the PIC 1 formulation under fed conditions. Period 3: Danicopan as the PIC 1 formulation under fasted conditions. There will be a washout period of at least 5 days between each danicopan dosing.

Drug: Danicopan: Powder-In-Capsule 1; Drug: Danicopan: Tablet

Part 2: Sequence 1

EXPERIMENTAL

Participants will receive danicopan once each period as a single oral dose under fasted or fed conditions as follows: Period 1: Danicopan as the PIC 2 formulation under fed conditions. Period 2: Danicopan as the PIC 2 formulation under fasted conditions. Period 3: Danicopan as a tablet under fed conditions. There will be a washout period of at least 5 days between each danicopan dosing.

Drug: Danicopan: Powder-In-Capsule 2; Drug: Danicopan: Tablet

Part 2: Sequence 2

EXPERIMENTAL

Participants will receive danicopan once each period as a single oral dose under fasted or fed conditions as follows: Period 1: Danicopan as the PIC 2 formulation under fasted conditions. Period 2: Danicopan as a tablet under fed conditions. Period 3: Danicopan as the PIC 2 formulation under fed conditions. There will be a washout period of at least 5 days between each danicopan dosing.

Drug: Danicopan: Powder-In-Capsule 2; Drug: Danicopan: Tablet

Part 2: Sequence 3

EXPERIMENTAL

Participants will receive danicopan once each period as a single oral dose under fasted or fed conditions as follows: Period 1: Danicopan as a tablet under fed conditions. Period 2: Danicopan as the PIC 2 formulation under fed conditions. Period 3: Danicopan as the PIC 2 formulation under fasted conditions. There will be a washout period of at least 5 days between each danicopan dosing.

Drug: Danicopan: Powder-In-Capsule 2; Drug: Danicopan: Tablet

Interventions

Danicopan: Powder-In-Capsule 1 DRUG

Danicopan (200 milligrams) will be administered orally on Day 1.

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

Part 1: Sequence 1; Part 1: Sequence 2; Part 1: Sequence 3

Danicopan: Powder-In-Capsule 2 DRUG

Danicopan (200 milligrams) will be administered orally on Day 1.

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

Part 2: Sequence 1; Part 2: Sequence 2; Part 2: Sequence 3

Danicopan: Tablet DRUG

Danicopan (200 milligrams) will be administered orally on Day 1.

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

Part 1: Sequence 1; Part 1: Sequence 2; Part 1: Sequence 3; Part 2: Sequence 1; Part 2: Sequence 2; Part 2: Sequence 3

Eligibility Criteria

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

You may qualify if:

• No clinically significant findings at screening (medical history, clinical laboratory profiles, and electrocardiograms).
• Body mass index in the range of 18.0 to 32.0 kilograms (kg)/meter squared, inclusive, with a minimum body weight of 50.0 kg at screening.
• Female participants of childbearing potential must either agree to abstinence or to use, with their male partner, a highly effective method of contraception .
• Non-sterile male participants must agree to abstinence or use a highly effective method of contraception.

You may not qualify if:

• History of any medical or psychiatric condition or disease that might limit 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 or presence of drug or alcohol abuse within previous 2 years, current tobacco user, or positive drugs-of-abuse screen or alcohol screen at screening or Day -1 of Period 1.
• History of meningococcal infection, or a first-degree relative with a history of meningococcal infection.
• History of procedures that could alter absorption or excretion of orally administered drugs.
• History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs.
• Body temperature ≥ 38.0°Celcius at screening or prior to first dosing or history of febrile illness, or other evidence of infection, within 14 days prior to (first) dosing.
• 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 before first dosing, whichever is longer.
• Donation of whole blood from 3 months prior to first dosing, or of plasma from 30 days before first dosing, receipt of blood products within 6 months prior to first dosing, or receipt of a vaccine within 30 days prior to first dosing.
• Is a female with a positive pregnancy test or who is lactating.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead
• Celerion: collaborator

Study Sites (1)

Clinical Trial Site

Tempe, Arizona, 85283, 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: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: October 30, 2020
• Study Start: October 20, 2020
• Primary Completion: December 7, 2020
• Study Completion: December 7, 2020
• Last Updated: April 15, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)