An Open-Label Phase 1 Study to Evaluate the Pharmacokinetics and Drug-Drug Interactions of Setanaxib in Healthy Adult Male and Female Subjects
Overview
- Phase
- Phase 1
- Intervention
- Setanaxib
- Conditions
- Phase 1
- Sponsor
- Calliditas Therapeutics AB
- Enrollment
- 64
- Locations
- 1
- Primary Endpoint
- Dose proportionality of setanaxib tablets after single oral administration of different doses.
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The study is a monocentric, open label, phase 1 study to evaluate the pharmacokinetics, and in particular the dose proportionality of setanaxib and its metabolites after a single oral dose (400 mg, 800 mg, 1200 mg, and 1600 mg) (Part 1) and after multiple oral doses (Part 2).
Detailed Description
The study is a monocentric, open label, phase 1 study to evaluate the pharmacokinetics, and in particular the dose proportionality of setanaxib and its metabolites after a single oral dose (400 mg, 800 mg, 1200 mg, and 1600 mg) (Part 1) and after multiple oral doses (Part 2). The study will include 2 parts conducted in separate cohorts of subjects. * Part 1 of the study will be an open label, single dose study evaluating the pharmacokinetics, and in particular the dose proportionality of setanaxib formulated as tablets, in 4 separate cohorts of 6 to 8 healthy adult subjects * Part 2 of the study will assess the pharmacokinetics of setanaxib tablets, expand the evaluation of potential drug-drug interactions, and assess the safety of setanaxib tablets at doses up to 1600mg/day for 14 days in separate 2 cohorts. The evaluation of drug-drug interactions will be carried out only at the top dose. Accordingly, a larger cohort (i.e. 16 subjects) will be included in Cohort 7.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy adult male or female aged 18 to 49 years
- •Provision of written informed consent to participate as shown by a signature on the subject consent form
- •Smoke no more than 5 cigarettes a day are permitted. Smocking (including the use of smocking substitute e.g. nicotine patch) is not permitted from screening to the end of study visit
- •Body weight of at least 45kg and a BMI included between 18.0 and 35.0 kg/m2
- •Female subjects of childbearing potential must use a highly effective method of contraception to prevent pregnancy for 4 weeks before inclusion and must agree to continue strict contraception for 30 days after last administration of IMP. Male participants with female partners of childbearing potential must be willing to use a condom and require their partner to use an additional form of adequate contraception as approved by the Investigator. This requirement begins at the time of informed consent and ends at least 3 months after the last administration of IMP. Male study participants must also not donate sperm from baseline until 3 months after the last administration of IMP.
- •Considered as healthy after a comprehensive clinical assessment (detailed medical history and complete physical examination)
- •Normal Blood Pressure (BP) and Heart Rate (HR) at the screening visit after 10 minutes in supine position.
- •Normal ECG recording on a 12-lead ECG at the screening visit:
- •Laboratory parameters within the normal range of the laboratory (hematological, blood chemistry tests, urinalysis). Individual values out of the normal range can be accepted if judged non-clinically significant by the Investigator
- •Has not consumed and agrees to abstain from taking any dietary supplements or non-prescription drugs over the 7 days prior to screening.
Exclusion Criteria
- •Have already received setanaxib
- •Contraindication(s) for any of the substrates used in the study
- •Any history or presence of cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurologic, psychiatric, systemic or infectious disease
- •Any history of severe cardiovascular disease, and any personal or family history of long QT syndrome, or evidence of abnormalities in cardiac conduction
- •Frequent headaches and / or migraine, recurrent nausea and / or vomiting
- •Symptomatic hypotension whatever the decrease of blood pressure or asymptomatic postural hypotension defined by a decrease in SBP or DBP equal to or greater than 20 mmHg within two minutes when changing from the supine to the standing position
- •Blood donation (including in the frame of a clinical study) within 2 months before administration;
- •General anesthesia within 3 months before administration
- •Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician
- •Inability to abstain from intensive muscular effort
Arms & Interventions
Part 1- Cohort 1
Single oral dose of 400 mg Setanaxib administered as 1x400 mg tablet in fasting conditions.
Intervention: Setanaxib
Part 1- Cohort 2
Single oral dose of 800 mg Setanaxib administered as 2x400 mg tablet in fasting conditions.
Intervention: Setanaxib
Part 1- Cohort 3
Single oral dose of 1200 mg Setanaxib administered as 3x400 mg tablet in fasting conditions.
Intervention: Setanaxib
Part 1- Cohort 4
Single oral dose of 1600 mg Setanaxib administered as 4x400 mg tablet in fasting conditions.
Intervention: Setanaxib
Part 2- Cohort 5
Repeated 10-Day dosing of 1200mg/day of Setanaxib administered as 2x400mg tablet in the morning and as 1x400mg tablet in the evening in fedding conditions.
Intervention: Setanaxib
Part 2- Cohort 6
Repeated 10-Day dosing of 1600mg/day of Setanaxib administered as 2x400mg tablet in the morning and as 2x400mg tablet in the evening in fedding conditions.
Intervention: Setanaxib
Cohort 7
Repeated 10-Day dosing of 1600mg/day of Setanaxib administered as 2x400mg tablet in the morning and as 2x400mg tablet in the evening in fedding conditions. Additionnaly, this cohort includes the evaluation of potential Drug-Drug interactions with CYPs and transporters.
Intervention: Setanaxib
Outcomes
Primary Outcomes
Dose proportionality of setanaxib tablets after single oral administration of different doses.
Time Frame: 144 hours
Measure the AUC and bioavailability (particularly the dose proportionality) of setanaxib tablets, after single oral administration of different doses (400, 800, 1200 and 1600mg) in healthy adult male and female subjects.
Drug-drug interactions of multiple oral administrations of setanaxib with 5 drugs that interact with CYP3A4, OAT1, OAT3, 2C9 and 2C19.
Time Frame: 14 days
Measure the changes in AUC of 5 drugs that interact with CYP3A4, OAT1, OAT3, 2C9 and 2C19 in healthy adult male (8) and female (8) subjects after multiple administrations of Setanaxib at dose of 1600mg only (cohort 6) or 800mg (cohort 7).
Assessment of safety after multiple oral administration of different doses of setanaxib.
Time Frame: 10 days
To evaluate the biological, physiological and treatment-related adverse events of setanaxib after multiple oral administration doses up to 1600 mg/day in healthy male and female subjects.
Secondary Outcomes
- Assessment of safety after single oral administration of different doses of setanaxib.(144 hours)
- Dose proportionality of setanaxib tablets after multiple oral administration of different doses.(10 days)