Study of Multiple Doses of Danicopan in Healthy Participants

Study Overview
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Brief Summary
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This was a multiple ascending dose, randomized, double-blind study assessing the safety, tolerability, pharmacokinetics, and pharmacodynamics of danicopan in healthy participants. Four different doses (75 milligrams [mg], 200 mg, 500 mg, 800 mg) and dose-matched placebo were administered under fasted conditions.

Official Title
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A Multiple Ascending Dose Study To Assess Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of ACH-0144471 In Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Danicopan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy was defined as having no clinically relevant abnormalities identified by a detailed medical history, physical exam, blood pressure and heart 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 (including gastrectomy and cholecystectomy). Body temperature greater than or equal to 38°Celcius on Day -1 or Day 1, Hour 0; history of febrile illness or other evidence of infection within 14 days prior to first study drug administration. Current tobacco/nicotine user; consumption of any alcohol within 72 hours before first study drug administration or have 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.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: 200 mg<br>All participants under fasted conditions received 200 mg of danicopan or placebo twice daily (BID) over a 14-day period. | Drug: Danicopan<br> <br> * Other names: 4471;Drug: Placebo<br> <br> |
| Experimental: Cohort 2: 500 mg<br>All participants under fasted conditions received 500 mg of danicopan or placebo BID over a 14-day period. | Drug: Danicopan<br> <br> * Other names: 4471;Drug: Placebo<br> <br> |
| Experimental: Cohort 3: 800 mg<br>All participants under fasted conditions received 800 mg of danicopan or placebo BID over a 14-day period. | Drug: Danicopan<br> <br> * Other names: 4471;Drug: Placebo<br> <br> |
| Experimental: Cohort 4: 75 mg<br>All participants under fasted conditions received 75 mg of danicopan or placebo thrice daily (TID) over a 7-day period. | Drug: Danicopan<br> <br> * Other names: 4471;Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) Of Danicopan |  | Up to 16 hours postdose | 
| Time To Maximum Observed Plasma Concentration (Tmax) Of Danicopan |  | Up to 16 hours postdose | 
| Area Under The Plasma Concentration Versus Time Curve Over The Dosing Interval (AUCtau) Of Danicopan |  | Up to 16 hours postdose | 
| Activity Of Danicopan As Measured By Alternative Pathway (AP) Wieslab Assay |  | Up to 16 hours postdose | 
| Relationship Between AP Inhibition And Danicopan Plasma Concentrations |  | Up to 16 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Danicopan, ALXN2040, ACH-0144471, Factor D Inhibitor, Pharmacokinetics, Pharmacodynamics, Ascending Dose