Study to Evaluate the Pharmacokinetics and Drug-Drug Interactions of Setanaxib in Healthy Adult Male and Female Subjects

NCT04327089 | Completed Phase 1 FDA Drug

• 1 other identifier: GSN000310
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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).

Conditions

Phase 1

Outcome Measures

Primary Outcomes (3)

• Dose proportionality of setanaxib tablets after single oral administration of different doses.

  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.

  144 hours

• Drug-drug interactions of multiple oral administrations of setanaxib with 5 drugs that interact with CYP3A4, OAT1, OAT3, 2C9 and 2C19.

  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).

  14 days

• Assessment of safety after multiple oral administration of different doses of setanaxib.

  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.

  10 days

Secondary Outcomes (2)

• 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

Study Arms (7)

Part 1- Cohort 1

EXPERIMENTAL

Single oral dose of 400 mg Setanaxib administered as 1x400 mg tablet in fasting conditions.

Drug: Setanaxib

Part 1- Cohort 2

EXPERIMENTAL

Single oral dose of 800 mg Setanaxib administered as 2x400 mg tablet in fasting conditions.

Drug: Setanaxib

Part 1- Cohort 3

EXPERIMENTAL

Single oral dose of 1200 mg Setanaxib administered as 3x400 mg tablet in fasting conditions.

Drug: Setanaxib

Part 1- Cohort 4

EXPERIMENTAL

Single oral dose of 1600 mg Setanaxib administered as 4x400 mg tablet in fasting conditions.

Drug: Setanaxib

Part 2- Cohort 5

EXPERIMENTAL

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.

Drug: Setanaxib

Part 2- Cohort 6

EXPERIMENTAL

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.

Drug: Setanaxib

Cohort 7

EXPERIMENTAL

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.

Drug: Setanaxib

Interventions

Setanaxib DRUG

Nox 1/4 inhibitor

Also known as: GKT137831

Cohort 7; Part 1- Cohort 1; Part 1- Cohort 2; Part 1- Cohort 3; Part 1- Cohort 4; Part 2- Cohort 5; Part 2- Cohort 6

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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.
• Has not consumed and agrees to abstain from taking any prescription drugs except contraception.
• Has not consumed alcohol containing beverages over the 48 hours prior to hospitalization
• Has not consumed grapefruit or grapefruit juice over the 48 hours prior to hospitalization
• Has the ability to understand the requirements of the study and is willing to comply with all study procedures
• Registered with the French Social Security in agreement with the French law on biomedical experimentation and register to the "Fichier national des personnes qui se prêtent à des recherches biomédicales"

You may not qualify if:

• 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
• No possibility of contact in case of emergency
• Any drug intake (except paracetamol or oral contraception) during the last month prior to the first administration
• History or presence of drug or alcohol abuse (alcohol consumption \> 40 grams / day)
• Excessive consumption of beverages with xanthine bases (\> 4 cups or glasses / day) during the last 30 days
• Positive Hepatitis B surface (HBs) antigen or anti Hepatitis C Virus (HCV) antibody, or positive results for Human Immunodeficiency Virus (HIV) 1 or 2 tests

Sponsors & Collaborators

• Calliditas Therapeutics AB: lead

Study Sites (1)

Eurofins Optimed

Gières, 38610, France

Location

Related Publications (1)

• Gage MC, Thippeswamy T. Inhibitors of Src Family Kinases, Inducible Nitric Oxide Synthase, and NADPH Oxidase as Potential CNS Drug Targets for Neurological Diseases. CNS Drugs. 2021 Jan;35(1):1-20. doi: 10.1007/s40263-020-00787-5. Epub 2021 Jan 30.

  PMID: 33515429 DERIVED

MeSH Terms

Interventions

setanaxib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-Label Phase 1 Study

Study Record Dates

• First Submitted: March 12, 2020
• First Posted: March 30, 2020
• Study Start: June 24, 2020
• Primary Completion: March 23, 2021
• Study Completion: March 23, 2021
• Last Updated: June 30, 2022

Record last verified: 2021-05

Locations

FR (1)