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Safety and Pharmacokinetics of VT-1598

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ClinicalTrials.gov Identifier: NCT04208321
Recruitment Status : Recruiting
First Posted : December 23, 2019
Last Update Posted : October 23, 2020
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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.

Condition or disease Intervention/treatment Phase
Coccidioidomycosis Other: Placebo Drug: VT-1598 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : May 26, 2020
Estimated Primary Completion Date : October 31, 2020
Estimated Study Completion Date : December 15, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Valley Fever

Arm Intervention/treatment
Experimental: Cohort 1
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.
Other: Placebo
Placebo will be supplied as matching tablets (to 40 mg and 80 mg VT-1598 tablets) containing the inactive components of VT-1598.

Drug: VT-1598
VT-1598 is a novel oral agent for the treatment of fungal infections. It will be supplied as 40 mg and 80 mg tablets.

Experimental: Cohort 2
80 mg (2 tablets 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.
Other: Placebo
Placebo will be supplied as matching tablets (to 40 mg and 80 mg VT-1598 tablets) containing the inactive components of VT-1598.

Drug: VT-1598
VT-1598 is a novel oral agent for the treatment of fungal infections. It will be supplied as 40 mg and 80 mg tablets.

Experimental: Cohort 3
160 mg (4 tablets 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.
Other: Placebo
Placebo will be supplied as matching tablets (to 40 mg and 80 mg VT-1598 tablets) containing the inactive components of VT-1598.

Drug: VT-1598
VT-1598 is a novel oral agent for the treatment of fungal infections. It will be supplied as 40 mg and 80 mg tablets.

Experimental: Cohort 4
320 mg (4 tablets of 80 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.
Other: Placebo
Placebo will be supplied as matching tablets (to 40 mg and 80 mg VT-1598 tablets) containing the inactive components of VT-1598.

Drug: VT-1598
VT-1598 is a novel oral agent for the treatment of fungal infections. It will be supplied as 40 mg and 80 mg tablets.

Experimental: Cohort 5
640 mg (8 tablets of 80 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.
Other: Placebo
Placebo will be supplied as matching tablets (to 40 mg and 80 mg VT-1598 tablets) containing the inactive components of VT-1598.

Drug: VT-1598
VT-1598 is a novel oral agent for the treatment of fungal infections. It will be supplied as 40 mg and 80 mg tablets.

Experimental: Cohort 6
160 mg (4 tablets of 40 mg) of VT-1598 administered orally as a single dose, n=6, or matching placebo, n=2, after high-calorie, high-fat meal on Day 1 in a double-blind manner.
Other: Placebo
Placebo will be supplied as matching tablets (to 40 mg and 80 mg VT-1598 tablets) containing the inactive components of VT-1598.

Drug: VT-1598
VT-1598 is a novel oral agent for the treatment of fungal infections. It will be supplied as 40 mg and 80 mg tablets.




Primary Outcome Measures :
  1. Occurrence of Adverse Events (AEs) for single oral dose of VT-1598 administered after a high-fat, high calorie meal [ Time Frame: Day 1 through Day 21 ]
  2. Occurrence of Adverse Events (AEs) for single-ascending fasting oral doses of VT-1598 [ Time Frame: Day 1 through Day 21 ]
  3. Occurrence of changes in clinical laboratory tests from baseline for single-ascending fasting oral doses of VT-1598 [ Time Frame: Day -1 through Day 21 ]
  4. Occurrence of changes in clinical laboratory tests from baseline for single oral dose of VT-1598 administered after a high-fat, high calorie meal [ Time Frame: Day -1 through Day 21 ]
  5. Occurrence of ECG changes from baseline for single oral dose of VT-1598 administered after a high-fat, high calorie meal [ Time Frame: Day 1 through Day 21 ]
  6. Occurrence of ECG changes from baseline for single-ascending fasting oral doses of VT-1598 [ Time Frame: Day 1 through Day 21 ]
  7. Occurrence of vital sign changes from baseline for single oral dose of VT-1598 administered after a high-fat, high calorie meal [ Time Frame: Day -1 through Day 21 ]
  8. Occurrence of vital sign changes from baseline for single-ascending fasting oral doses of VT-1598 [ Time Frame: Day -1 through Day 21 ]

Secondary Outcome Measures :
  1. Plasma VT-11134 levels following consumption of a high-fat, high calorie meal [ Time Frame: Day 1 through Day 21 ]
  2. Plasma VT-11134 levels when fasting [ Time Frame: Day 1 through Day 21 ]
  3. Plasma VT-1598 levels following consumption of a high-fat, high calorie meal [ Time Frame: Day 1 through Day 21 ]
  4. Plasma VT-1598 levels when fasting [ Time Frame: Day 1 through Day 21 ]
  5. Urine VT-11134 levels following consumption of a high-fat, high calorie meal [ Time Frame: Day 1 through Day 4 ]
  6. Urine VT-11134 levels when fasting [ Time Frame: Day 1 through Day 4 ]
  7. Urine VT-1598 levels following consumption of a high-fat, high calorie meal [ Time Frame: Day 1 through Day 4 ]
  8. Urine VT-1598 levels when fasting [ Time Frame: Day 1 through Day 4 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04208321


Contacts
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Contact: Cassandra Charis Key Cassandra.Key@iconplc.com

Locations
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United States, Texas
ICON Early Phase Services Clinical Research Unit Recruiting
San Antonio, Texas, United States, 78209-1015
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04208321    
Other Study ID Numbers: 17-0087
HHSN272201500007I
First Posted: December 23, 2019    Key Record Dates
Last Update Posted: October 23, 2020
Last Verified: January 31, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Adults
Healthy
Pharmacokinetics
Phase 1
Safety
Single Oral Doses
Tolerability
VT-1598
Additional relevant MeSH terms:
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Coccidioidomycosis
Coccidiosis
Mycoses
Protozoan Infections
Parasitic Diseases