Healthy participants Other
Conditions
Interventions
Healthy participants are planned to be enrolled in this study. Participants will be randomised using a computer-generated randomisation schedule.
Part 1: Single Ascending Dose and Pilot Food Effect
P
Sponsors
BioCryst Pharmaceuticals (United States)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to provide written, informed consent. 2. Healthy male and non-pregnant, non-lactating female participants aged 18 to 55 years. 3. Body mass index (BMI) between 18 and 32 kilogram per meter square (kg/m2), inclusive. 4. Estimated glomerular filtration rate (eGFR) of = 80 milliliter per minute per 1.73 meter square (mL/min/1.73m2) as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. 5. Females of childbearing potential and males with female partners of childbearing potential must agree to use a highly effective contraceptive method, from screening until 30 days after discharge from the Clinical Research Unit (CRU) 6. In the opinion of the investigator, the participant is expected to adequately comply with all required study procedures and restrictions for the duration of the study. 7. Part 2 and Part 3 Cohort 2 only: must have adequate prophylaxis against Neisseria meningitidis infection. 8. Part 3 only: Japanese participants must be first generation: born in Japan; not having lived outside Japan for more than 5 years; able to trace maternal and paternal Japanese ancestry; with no significant change in lifestyle since leaving Japan (at least one Japanese meal consumed per day).
Exclusion criteria
Exclusion criteria: 1. Any clinically significant medical or psychiatric condition or medical history that, in the opinion of the investigator or sponsor, would interfere with the participant’s ability to participate in the study or increase the risk of participation for that participant. Participants with Gilbert’s syndrome and those who have had a cholecystectomy are not allowed. 2. Bacterial, viral, or fungal infection, or any other serious infection, with incompletely resolved signs and symptoms within 30 days prior to screening. This includes suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, persistent or recurrent positive tests for SARS-CoV-2 nucleic acids or antigens, and persistent or recurrent fever or other symptoms or signs consistent with multisystem inflammatory syndrome in adults or any other post COVID-19 syndrome. 3. Clinically significant abnormal bedside ECG at screening. This includes but is not limited to a QTcF > 450 milliseconds (msec) in males or > 470 msec in females, a Pulse rate (PR) 204 msec, a Auricle diastole Auricular repolarization Ventricular depolarization Cardiac cycle (QRS) 120 msec, or ventricular and/or atrial premature contractions that are more frequent than occasional, and/or as couplets or higher in grouping. 4. History of kidney-related diseases and disorders, including acute kidney injury. 5. History or current diagnosis of non-alcoholic steatohepatitis (NASH). 6. Any clinically significant history of a cardiovascular abnormality, including but not limited to angina, known coronary artery disease, myocardial infarction, syncope, clinically significant cardiac arrhythmias, left ventricular hypertrophy, cardiomyopathy, and aortic stenosis. 7. Known family history of sudden cardiac death in a first-degree relative. 8. History of or current implanted defibrillator or pacemaker. 9. Any laboratory parameter at screening and Day -1 that, in the opinion of the investigator or sponsor, is clinically significant and relevant for this study. This includes but is not limited to cholesterol (low-density lipoprotein, high-density lipoprotein, and total) or triglycerides > 1.5 × Upper limit of normal (ULN) at screening or Day -1 or creatine kinase > 1.5 × ULN on Day -1. Enrollment of a participant with laboratory value(s) minimally outside of the reference range may be permissible if the abnormality is documented by the investigator to not be of clinical significance. 10. Aspartate transaminase (AST), Alanine aminotransferase (ALT), or total bilirubin value > ULN, obtained during screening or Day -1. 11. Use of any over-the-counter medications, prescribed medications, vitamins, or herbal products within 14 days prior to Day 1 (other than up to 2 grams per day paracetamol/acetaminophen, contraceptives, COVID-19 vaccines permitted by the protocol, and vaccines against N. meningitidis types A, C, W, Y, and B [Part 2 and Part 3 Cohort 2 only]. 12. Participant has received a live attenuated vaccine (also applicable to COVID-19 vaccines that may become available during the conduct of the study) within 30 days prior to Day 1 or has received another type of vaccine within 14 days prior to Day 1, except vaccinations against N.meningitidis. COVID-19 vaccination with authorized or available vaccines is prohibited within 3 days prior to Day 1. 13. Use of a medication or herbal product that is clinically known to inhibit or induce metabolic enzymes or transporters w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Parts 1 and 4: The number of participants with treatment-emergent adverse events (TEAEs) measured using case reports from day 1 up to day 18 2. Part 2: The number of participants with TEAEs measured using case reports from day 1 up to day 45 3. Parts 1 and 4: Change from baseline (day 1) in vital signs and physical examination (blood pressure, temperature, heart rate, height, weight and body mass index [BMI] ) will be measured manually or using an automatic blood pressure monitor up to day 18 4. Part 2: Change from baseline (day 1) in vital signs and physical examination (blood pressure, temperature, heart rate, height, weight and BMI) will be measured manually or using an automatic blood pressure monitor up to day 45 5. Parts 1 and 4: The number of participants with abnormality in bedside 12-lead electrocardiogram (ECG) parameters using a standard bedside 12-lead ECG machine from day 1 up to day 18 6. Part 2: The number of participants with abnormality in bedside 12-lead ECG parameters using a standard bedside 12-lead ECG machine from day 1 up to day 45 7. Parts 1 and 4: The number of participants with abnormality in clinical laboratory parameters (hematology, urinalysis and coagulation) using blood and urine samples from day 1 up to day 18 8. Part 2: The number of participants with abnormality in clinical laboratory parameters (hematology, urinalysis and coagulation) using blood and urine samples from day 1 up to day 45 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Part 3 (Japanese participants): Number of participants with TEAEs from day 1 up to day 45 2. Part 3 (Japanese participants): Change from baseline in vital signs and physical examination (blood pressure, temperature, heart rate, height, weight and BMI) will be measured manually or using an automatic blood pressure monitor up to day 45 3. Part 3 (Japanese participants): Number of participants with abnormality in bedside 12-lead ECG parameters using a standard bedside 12-lead ECG machine from day 1 up to day 45 4. Part 3 (Japanese participants): Number of participants with abnormality in clinical laboratory parameters (hematology, urinalysis and coagulation) using blood and urine samples from day 1 up to day 45 5. Parts 1 to 4: Pharmacokinetic (PK) parameters for BCX10013 and its metabolite BCX13741 will be evaluated by noncompartmental analysis using blood and urine samples collected at pre-dose and at multiple time points, up to day 31 6. Parts 1 and 2 and Part 3 cohort 1: Dose proportionality for PK parameters of BCX10013 and its metabolite BCX13741 will be assessed by a power model using blood samples collected at pre-dose and at multiple time points, up to day 31 7. Parts 1 to 4: Effect of BCX10013 on pharmacodynamic (PD) and biomarkers will be evaluated as change over time in PD biomarkers using blood and urine samples at pre-dose and at multiple timepoints, up to day 31 | — |
Countries
England, Netherlands, United Kingdom
Contacts
Public ContactData Disclosure -
Outcome results
None listed