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

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ClinicalTrials.gov Identifier: NCT04327089
Recruitment Status : Recruiting
First Posted : March 30, 2020
Last Update Posted : January 14, 2021
Sponsor:
Information provided by (Responsible Party):
Genkyotex SA

Tracking Information
First Submitted Date  ICMJE March 12, 2020
First Posted Date  ICMJE March 30, 2020
Last Update Posted Date January 14, 2021
Actual Study Start Date  ICMJE June 24, 2020
Estimated Primary Completion Date April 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2020)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 27, 2020)
  • Part 1 - Single Ascending Dose [ 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.
  • Part 2 - Multiple Ascending Dose [ Time Frame: 14 days ]
    Measure the AUC and bioavailability (particularly the dose proportionality) of setanaxib tablets after multiple oral administration at 2 different doses in healthy adult male and female subjects.
  • Part 2 - Multiple Ascending Dose [ 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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2020)
  • Assessment of safety after single oral administration of different doses of setanaxib. [ Time Frame: 144 hours ]
    To evaluate the biological, physiological and treatment-related adverse events of setanaxib tablets after single oral administration of 4 different doses in healthy male and female subjects.
  • Dose proportionality of setanaxib tablets after multiple oral administration of different doses. [ Time Frame: 10 days ]
    Measure the AUC and bioavailability (particularly the dose proportionality) of setanaxib tablets after multiple oral administration at 2 different doses in healthy adult male and female subjects.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2020)
  • Part 1 - Single Ascending Dose [ Time Frame: 144 hours ]
    To evaluate the biological, physiological and treatment-related adverse events of setanaxib tablets after single oral administration of 4 different doses in healthy male and female subjects.
  • Part 2 - Multiple Ascending Dose [ Time Frame: 14 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Pharmacokinetics and Drug-Drug Interactions of Setanaxib in Healthy Adult Male and Female Subjects
Official Title  ICMJE An Open-Label Phase 1 Study to Evaluate the Pharmacokinetics and Drug-Drug Interactions of Setanaxib in Healthy Adult Male and Female Subjects
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
Open-Label Phase 1 Study
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Phase 1
Intervention  ICMJE Drug: Setanaxib
Nox 1/4 inhibitor
Other Name: GKT137831
Study Arms  ICMJE
  • Experimental: Part 1- Cohort 1
    Single oral dose of 400 mg Setanaxib administered as 1x400 mg tablet in fasting conditions.
    Intervention: Drug: Setanaxib
  • Experimental: Part 1- Cohort 2
    Single oral dose of 800 mg Setanaxib administered as 2x400 mg tablet in fasting conditions.
    Intervention: Drug: Setanaxib
  • Experimental: Part 1- Cohort 3
    Single oral dose of 1200 mg Setanaxib administered as 3x400 mg tablet in fasting conditions.
    Intervention: Drug: Setanaxib
  • Experimental: Part 1- Cohort 4
    Single oral dose of 1600 mg Setanaxib administered as 4x400 mg tablet in fasting conditions.
    Intervention: Drug: Setanaxib
  • Experimental: 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: Drug: Setanaxib
  • Experimental: 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: Drug: Setanaxib
  • Experimental: 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: Drug: Setanaxib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 5, 2020)
64
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2020)
54
Estimated Study Completion Date  ICMJE April 15, 2021
Estimated Primary Completion Date April 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Healthy adult male or female aged 18 to 49 years
  2. Provision of written informed consent to participate as shown by a signature on the subject consent form
  3. 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
  4. Body weight of at least 45kg and a BMI included between 18.0 and 35.0 kg/m2
  5. 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.
  6. Considered as healthy after a comprehensive clinical assessment (detailed medical history and complete physical examination)
  7. Normal Blood Pressure (BP) and Heart Rate (HR) at the screening visit after 10 minutes in supine position.
  8. Normal ECG recording on a 12-lead ECG at the screening visit:
  9. 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
  10. Has not consumed and agrees to abstain from taking any dietary supplements or non-prescription drugs over the 7 days prior to screening.
  11. Has not consumed and agrees to abstain from taking any prescription drugs except contraception.
  12. Has not consumed alcohol containing beverages over the 48 hours prior to hospitalization
  13. Has not consumed grapefruit or grapefruit juice over the 48 hours prior to hospitalization
  14. Has the ability to understand the requirements of the study and is willing to comply with all study procedures
  15. 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"

Exclusion Criteria:

  1. Have already received setanaxib
  2. Contraindication(s) for any of the substrates used in the study
  3. Any history or presence of cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurologic, psychiatric, systemic or infectious disease
  4. Any history of severe cardiovascular disease, and any personal or family history of long QT syndrome, or evidence of abnormalities in cardiac conduction
  5. Frequent headaches and / or migraine, recurrent nausea and / or vomiting
  6. 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
  7. Blood donation (including in the frame of a clinical study) within 2 months before administration;
  8. General anesthesia within 3 months before administration
  9. Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician
  10. Inability to abstain from intensive muscular effort
  11. No possibility of contact in case of emergency
  12. Any drug intake (except paracetamol or oral contraception) during the last month prior to the first administration
  13. History or presence of drug or alcohol abuse (alcohol consumption > 40 grams / day)
  14. Excessive consumption of beverages with xanthine bases (> 4 cups or glasses / day) during the last 30 days
  15. 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
  16. Positive results of screening for drugs of abuse
  17. Any contraindication to the administration of midazolam, adefovir, losartan, omeprazole, sitagliptin
  18. Subject who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development
  19. Currently in exclusion period from a previous study
  20. Administrative or legal supervision
  21. Subject who would receive more than 4500 euros as indemnities for his participation in biomedical study within the 12 last months, including the indemnities for the present study.
  22. Minor, pregnant or breast-feeding women, persons deprived of liberty by judicial or administrative decision, persons receiving psychiatric care and persons admitted to a health or social institution, adult subject to legal protection or unable to express consent.
  23. Positive results for SARS-CoV-2 tests.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 49 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Philippe WIESEL, MD +330673636721 ext +330673636721 philippe.wiesel@genkyotex.com
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04327089
Other Study ID Numbers  ICMJE GSN000310
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Genkyotex SA
Study Sponsor  ICMJE Genkyotex SA
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Genkyotex SA
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP