Clinical trial NCT04451434: Study of Danicopan in Participants of Japanese Descent
Official title: A Phase 1 Study to Determine the Safety, Tolerability, and Pharmacokinetics of Danicopan After Administration as an Oral Tablet in the Fed and Fasted States in Participants of Japanese Descent
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Factor D inhibitor
Complement
Danicopan
Pharmacokinetics
Japanese
Food
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-06-30
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Three-way crossover
Primary purpose: TREATMENT

Brief summary: This study will assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of danicopan after a single-dose oral administration under fed and fasting conditions to participants of Japanese descent.

Detailed description: This will be an open-label, randomized, single-dose, 3-period, 3-treatment crossover study in participants of Japanese descent.

On Day 1 of each period, participants will receive a single oral dose of 200 milligrams (mg) danicopan under fasting conditions, 200 mg danicopan under fed conditions, or 400 mg danicopan under fed conditions. Participants will receive each treatment once, according to the randomization schedule. There will be a washout period of at least 7 days between each dose of study intervention.

Safety will be assessed throughout the study.

Eligibility criteria: Inclusion Criteria:

1. Participants who are of Japanese descent defined as:

   * First generation (born to 2 Japanese parents and 4 Japanese grandparents)
   * Born in Japan, and not have lived outside Japan for greater than 10 years
   * Lifestyle, including diet, must not have significantly changed since leaving Japan
2. No clinically significant history or presence of electrocardiogram findings as judged by the Investigator at screening and prior to the first dose of study intervention in Period 1.
3. Body mass index in the range of 18.0 to 32.0 kilograms (kg)/meters squared, inclusive, with a minimum body weight of 50.0 kg at screening.

Exclusion Criteria:

1. Evidence of any clinically significant deviation from normal in clinical laboratory evaluations, as determined by the Investigator or designee.
2. History of any medical or psychiatric condition or disease that, in the opinion of the Investigator or designee, 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.
3. History or presence of clinically significant hypersensitivity or idiosyncratic reaction to the study interventions or related compounds or commonly used antibacterial agents.
4. History of meningococcal infection, or a first-degree relative with a history of meningococcal infection.
5. History of febrile illness, or other evidence of infection, within 14 days prior to the first dose of study intervention.
6. Any major surgery within 4 weeks of the first dose of study intervention.
7. Diagnosis or history of Gilbert's syndrome, in the opinion of the Investigator or designee.
8. Unable to refrain from or anticipates the use of any drug.
9. Receipt of a vaccine within 30 days prior to the first dose of study intervention.
10. Receipt of blood products within 6 months prior to the first dose of study intervention.
11. 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 the first dose of study intervention, whichever is longer.
12. Seated blood pressure is less than 90/40 millimeters of mercury (mmHg) or greater than 140/90 mmHg at screening.
13. Participants who test positive for human immunodeficiency virus, hepatitis B virus, and/or hepatitis C virus.
14. Current tobacco users and smokers or a positive cotinine test at screening.
15. Donation of whole blood from 3 months prior to the first dose of study intervention, or of plasma from 30 days prior to the first dose of study intervention.
16. Positive drugs of abuse screen at screening or Day -1 of Period 1.
17. Positive results for alcohol screen at screening or Day -1 of Period 1.
18. Is a female with a positive pregnancy test at screening or Day -1 of Period 1 or who is lactating, or who plan to become pregnant (within 5 months of screening).

Primary outcomes:
measure: Number Of Participants With Treatment-Emergent Adverse Events
timeFrame: Day 1 (after first dose) through safety follow-up (10 +/- 2 days after last dose)
measure: Area Under The Concentration Versus Time Curve (AUC) Of Danicopan In Both Fed And Fasted States
timeFrame: up to 72 hours postdose
measure: Maximum Observed Concentration (Cmax) Of Danicopan In Both Fed And Fasted States
timeFrame: up to 72 hours postdose
measure: Time To Maximum Observed Concentration (Tmax) Of Danicopan In Both Fed And Fasted States
timeFrame: up to 72 hours postdose
measure: Dose Proportionality Of Danicopan In Fed State Assessed by AUC
timeFrame: up to 72 hours postdose
measure: Dose Proportionality Of Danicopan In Fed State Assessed by Cmax
timeFrame: up to 72 hours postdose
Secondary outcomes:
measure: Activity Of Danicopan As Measured By Alternative Pathway Wieslab Assay
timeFrame: up to 72 hours postdose
measure: Complement Factor B Fraction b Levels
timeFrame: up to 72 hours postdose
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: Clinical Study Site
Study officials:
References: