Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Healthy males or healthy females of non-childbearing potential
Between 18 and 55 years of age, inclusive, at time of signing informed consent
Body mass index (BMI) of 18.0 to 30.0 kg/m2 as measured at screening
Must be willing and able to communicate and participate in the whole study
Must provide written informed consent
Must agree to adhere to the contraception requirements

Exclusion Criteria:

Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1
Subjects who are or are immediate family members of a study site employee or a sponsor employee
Subjects who have previously been enrolled (dosed) in this study; subjects who have previously received sparsentan
Evidence current SARS-CoV-2 infection
History of any drug or alcohol abuse in the past 2 years
Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type)
A confirmed positive alcohol breath test at screening or admission
Current smokers and those who have smoked within the last 3 months
A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission
Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 3 months

Females of childbearing potential:

A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration ≥40 IU/L)
Subjects who are pregnant or lactating and subjects with pregnant or lactating partners. All women must have a negative pregnancy test at admission
Subjects who do not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator or delegate at screening
Clinically significant abnormal clinical chemistry, hematology or urinalysis as judged by the investigator at screening
Serum alanine aminotransferase (ALT) > 1.5× upper limit of normal at screening
Serum potassium > upper limit of normal at screening
Confirmed positive drugs of abuse test result at screening or admission to Period 1
Corrected QT interval by Fridericia's formula (QTcF) greater than 450 msec; ventricular rate less than 40 per minute or greater than 90 per minute at screening or prior to dosing
For supine vital signs: systolic blood pressure less than 100 mmHg or greater than 140 mmHg (in subjects > 45 years of age up to 160 mmHg is acceptable); diastolic blood pressure less than 60 mmHg or over 90 mmHg at screening and pre-first dose.
Decrease in systolic blood pressure of 20 mmHg or more and/or decrease in diastolic blood pressure of 10 mmHg or more, measured after standing for approximately 2 to 5 min at screening and pre-dose in Period 1.
Increase in heart rate of over 30 bpm measured after standing for 2 to 5 min at screening and pre-dose Period 1
Any current or recent symptoms of postural hypotension or postural tachycardia at screening and pre-dose Period 1
Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
Evidence of renal impairment at screening, as indicated by an eGFR of <90 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) (2009) equation
History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator
Subjects with a history of cholecystectomy or gall stones
Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
Subjects with a history of any hypersensitivity to angiotensin receptor blockers, endothelin receptor antagonists or the suspension formulation excipients
Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active
Donation or loss of greater than 400 mL of blood within the previous 3 months
Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than 4 g of paracetamol per day or hormone replacement therapy [HRT]) in the 14 days before IMP administration. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as determined by the PI
Use of any medication, eg erythromycin, itraconazole, and gestodene, that is known to inhibit CYP3A4 within 14 days before IMP administration
Use of any medication or substance known to induce CYP3A4, eg St John's Wort, within 30 days before IMP administration
Failure to satisfy the investigator of fitness to participate for any other reason