Safety and Pharmacokinetics of VT-1598

Brief Title

Safety and Pharmacokinetics of VT-1598

Official Title

A Phase 1, First-In-Human, Randomized, Double-Blind, Placebo-Controlled, Single Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Single Oral Doses of VT-1598 in Healthy Adult Subjects

Brief Summary

      This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study
      in healthy adult subjects ages 18 - 45 years inclusive. It is designed to evaluate the safety
      and PK of single oral doses of VT-1598. Forty-eight subjects will be enrolled in the study at
      1 site in the US and randomized to receive either VT-1598 or placebo in 6 dosage cohorts
      (five fasted cohorts and one fed cohort). Each cohort will have 8 subjects; 6 subjects will
      receive a single oral dose of VT-1598 and 2 subjects will receive matching placebo. Cohorts 1
      - 5 will include 2 sentinel subjects randomized to different treatments. Cohort 6 (receiving
      treatment after being fed a high-calorie, high-fat meal) will not include sentinel subjects.
      Subjects will be admitted to the study site before dosing and remain at the study site for
      safety monitoring and PK assessments for at least 72 hours post-dose. Subjects will return to
      the study site on study Days 7, 14, and 21 for outpatient safety monitoring and PK
      assessments. There are no formal hypotheses being tested in this Phase 1 trial study. The
      primary objectives of this study are 1) to determine the safety of single-ascending oral
      doses of VT-1598 in healthy adult subjects in a fasted state, and 2) to determine the safety
      of single oral dose of VT-1598 in healthy adult subjects in a fed state.
    

Detailed Description

      This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study
      in healthy adult subjects ages 18 - 45 years inclusive. It is designed to evaluate the safety
      and PK of single oral doses of VT-1598. Forty-eight subjects will be enrolled in the study at
      1 site in the US and randomized to receive either VT-1598 or placebo in 6 dosage cohorts
      (five fasted cohorts and one fed cohort). Cohorts 1 - 4 will run sequentially, but Cohorts 5
      and 6 may be started concurrently. Each cohort will have 8 subjects; 6 subjects will receive
      a single oral dose of VT-1598 and 2 subjects will receive matching placebo. Cohorts 1 - 5
      will include 2 sentinel subjects randomized to different treatments. Cohort 6 (receiving
      treatment after being fed a high-calorie, high-fat meal) will not include sentinel subjects.
      VT-1598 will be administered in the following escalation schedule: Cohort 1 will receive 40
      mg dose, Cohort 2 will receive 80 mg dose, Cohort 3 will receive 160 mg dose, Cohort 4 will
      receive 320 mg dose, Cohort 5 will receive 640 mg dose, and Cohort 6 (fed cohort) will
      receive 160 mg dose. Subjects will be admitted to the study site before dosing and remain at
      the study site for safety monitoring and PK assessments for at least 72 hours post-dose.
      Subjects will return to the study site on study Days 7, 14, and 21 for outpatient safety
      monitoring and PK assessments. There are no formal hypotheses being tested in this Phase 1
      trial study. The primary objectives of this study are 1) to determine the safety of
      single-ascending oral doses of VT-1598 in healthy adult subjects in a fasted state, and 2) to
      determine the safety of single oral dose of VT-1598 in healthy adult subjects in a fed state.
      The secondary objectives of this study are 1) to determine the pharmacokinetic (PK) profile
      in plasma and urine of VT-1598 and its primary metabolite, VT-11134, in healthy adult
      subjects, and 2) to determine the effect of a high-fat, high-calorie meal on the PK profile
      of VT-1598 and VT-11134 when a single oral dose of VT-1598 is given.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Occurrence of Adverse Events (AEs) for single oral dose of VT-1598 administered after a high-fat, high calorie meal

Secondary Outcome

 Plasma VT-11134 levels following consumption of a high-fat, high calorie meal

Condition

Coccidioidomycosis

Intervention

Placebo

Study Arms / Comparison Groups

 Cohort 1
Description:  40 mg (1 tablet of 40 mg) of VT-1598 administered orally as a single dose, n=6 (1 sentinel, 5 non-sentinel), or matching placebo, n=2 (1 sentinel, 1 non-sentinel), while fasting on Day 1 in a double-blind manner.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Other

Estimated Enrollment

48

Start Date

September 29, 2020

Completion Date

July 31, 2021

Primary Completion Date

May 31, 2021

Eligibility Criteria

        Inclusion Criteria:

          1. Willing and able to provide written informed consent and authorization for use of
             protected health information.

          2. Willing and able to comply with protocol requirements, instructions, and
             protocol-stated restrictions (including confinement to the Clinical Research Unit
             (CRU)) and is likely to complete the study as planned.

          3. Male or female subjects, 18 - 45 years of age (inclusive).

          4. Subject is in good health to be safely enrolled in this protocol as determined by
             medical history and physical exam.

          5. Body Mass Index (BMI) of 18 - 35 kg / m^2, inclusive, and minimum weight of 50 kg.

          6. If a female participant is of childbearing potential*, she must use a highly effective
             contraceptive method** from 30 days before enrollment through the 3 months after
             dosing.

             *A woman is considered of childbearing potential unless post-menopausal (subject is at
             least 50 years old and has history of >/=2 years without menses without other known or
             suspected cause and has a Follicle Stimulating Hormone (FSH) level >40 IU/L), or
             permanently surgically sterilized.

             **A highly effective contraceptive method includes surgical sterilization methods such
             as tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful
             tubal obliteration (e.g., Essure(R)) with documented radiological confirmation test at
             least 90 days after the procedure, or long-acting reversible contraception
             (progestin-releasing subdermal implants, copper intrauterine devices (IUDs),
             levonorgesterel-releasing IUDs).

          7. Males* having sexual intercourse with women of childbearing potential must agree to
             consistent use of condoms from study product administration through 3 months after
             dosing**.

             *Including vasectomized men.

             **And must also agree to not donate sperm during the same time period.

          8. Subject has adequate venous access for blood collection.

        Exclusion Criteria:

          1. Has a chronic condition that may increase risk to subject or interfere with endpoint
             assessment (e.g., liver disease, kidney disease, immunodeficiency).

          2. Chronic condition diagnosed within 90 days of the screening visit.

          3. Unstable chronic disease* within 6 months of the screening visit.

             *As defined by need for medical intervention that lead to a change in medications
             and/or required hospitalization, surgery/procedure, or ED/urgent care visit

          4. History of psychiatric condition that has required hospitalization in the last 5 years
             or patient is considered unstable by study investigator.

          5. Any condition that in the opinion of the Investigator could significantly impact drug
             absorption, distribution, or elimination.

          6. Any out of normal range laboratory value* at screening or enrollment.

             *A laboratory value that is Grade 1 (with the exception of alanine aminotransferase
             (ALT), aspartate aminotransferase (AST), Total bilirubin, hemoglobin or serum
             creatinine) will be allowed if not considered to be clinically significant by the
             investigator.

          7. Abnormal Electrocardiograms (ECGs).

          8. Electrocardiographic QTcF interval >430 msec for males and >450 msec for females at
             Screening.

          9. Positive test for antibodies to Human Immunodeficiency Virus-1 (HIV-1), Human
             Immunodeficiency Virus-2 (HIV-2), Hepatitis B surface antigen (HBsAg), or Hepatitis C
             (HCV).

         10. Positive urine drug test. The drugs that will be screened for includes amphetamines,
             barbiturates , cocaine, opiates, cannabinoids, phencyclidine, and benzodiazepines.

         11. Female subject of childbearing potential who is pregnant*, lactating, or planning to
             become pregnant during the study period or 3 months after the final dose of study
             product.

             *Having a positive serum pregnancy test at the Screening Visit or any other specified
             time point prior to the dose of study product.

         12. Received any study product in a clinical trial within 30 days prior to Screening.

         13. Admitted or documented illicit drug use or alcohol abuse within 6 months prior to
             Screening or during their participation in the trial.

         14. Consumed alcohol within 72 hours of Day -1, until after the visit to the Clinical
             Research Unit (CRU) on Day 14 or have a positive alcohol test at Screening or on
             admission to the CRU.

         15. Tobacco* use within 90 days prior to the Screening Visit or while a subject is
             enrolled in the study or a positive urine drug test for cotinine.

             *Tobacco use includes vaping, smoking tobacco, the use of snuff and chewing tobacco,
             and other nicotine or nicotine- containing products

         16. Use of prescription drugs within 14 days prior to the dose of study product with the
             exception of hormonal contraceptives, which are permitted throughout the study.

         17. Received any non-prescription medications, vitamins, or dietary supplements* within 7
             days of dosing, unless prior approval is granted by both the Investigator and the
             Sponsor.

             *Excluded from this list is intermittent use of acetaminophen at doses of < / = 2 g /
             day or ibuprofen < / = 1200 mg / day. Herbal supplements must be discontinued 7 days
             prior to the dose of the study product.

         18. History of intolerance or hypersensitivity to azole antifungals.

         19. Blood donation or other significant blood loss within 60 days of screening and for the
             duration of the study.

         20. Inability or difficulty swallowing whole capsules/tablets and/or multiple
             capsules/tablets.

         21. Consumption of beverages and foods containing caffeine for 24 hours prior to Day -1
             until discharge from the CRU on Day 4.

         22. Consumption of grapefruit, or juices containing grapefruit or Seville oranges within 7
             days prior to the scheduled dose of the study product until after the visit to the CRU
             on Day 14.

         23. Subject has plans to enroll or is already enrolled in another clinical trial that
             could interfere with safety assessment of the investigational product at any time
             during the study period*.

             *Includes trials that have a study intervention such as a drug, biologic, or device

         24. Having dietary restrictions that would preclude the subject from participating in
             either fed or fasting cohorts.

         25. Having sensitivity or allergy to aspirin.
      

Gender

All

Ages

18 Years - 45 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

, , [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04208321

Organization ID

17-0087

Secondary IDs

HHSN272201500007I

Responsible Party

Sponsor

Study Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)


Study Sponsor

, , 


Verification Date

March 2021