Safety and Pharmacokinetics of VT-1598

NCT04208321 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 17-0087HHSN272201500007I
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Coccidioidomycosis

Keywords

Adults; Healthy; Pharmacokinetics; Phase 1; Safety; Single Oral Doses; Tolerability; VT-1598

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Unsolicited Adverse Events

  Adverse events (AEs) are defined as any untoward medical occurrence regardless of its causal relationship to study treatment. Number of participants with an AE are summarized by MedDRA System Organ Class (SOC). Each subject was counted once per SOC. If a condition was present at screening, it was not considered an AE unless the severity worsened.

  Day 1 through Day 21

• Number of Participants With Abnormal Chemistry Laboratory Toxicity Results

  Laboratory parameters and associated thresholds include albumin \<=3.4 g/dL, glucose \<= 69 mg/dL or \>=106 mg/dL, blood urea nitrogen (BUN) \>= 21 mg/dL, potassium \>=5.2 mEq/L or \<=3.4 mEq/L, calcium \< 8.7 mg/dL or \>=10.3 mg/dL, sodium \<=132 mEq/L or \>=144 mEq/L, total protein \<=5.9 g/dL, creatinine \>=1.3 mg/dL (male) or \>= 1.0 mg/dL (female), creatine phosphokinase \>= 308 U/L (male) or \>=192 U/L (female), phosphorus \<=2.4 mg/dL, alkaline phosphatase \>= 130 IU/L (males) or \>= 105 IU/L (female), aspartate aminotransferase \>= 39.9 U/L (male) or \>= 31.9 U/L (female), alanine aminotransferase \>=40.9 U/L (male) or \>= 32.9 U/L (female), total bilirubin \>=1.2 mg/dL, direct bilirubin \>=0.2 mg/dL, magnesium \<=1.6 mg/dL, and serum cortisol \<= 4 ug/dL. If a clinical chemistry laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.

  Baseline (Day -1) through Day 21

• Number of Participants With Abnormal Hematology Laboratory Toxicity Results

  Laboratory parameters and associated thresholds for adverse events include hemoglobin \<= 12.2 g/dL (male) or \<= 10.8 g/dL (female), hematocrit \<= 36.1 % (male) or \<= 32.6 % (female), lymphocyte count \<= 799 cell/mm3, neutrophil count \<= 1,299 cell/mm3 (African Americans) or \<= 1,699 cell/mm3 (all others), monocyte count \>= 1001 cell/mm3, eosinophil count \>= 871 cell/mm3, basophil count \>= 101 cell/mm3, platelet count \<= 150 x 10\^3/mm3, red blood cell (RBC) count \<= 4.1 x 10\^6/uL (male) or \<= 3.7 x 10\^6/uL (female), and white blood cell (WBC) count \>= 9,001 cell/mm3 or \<= 2,499 cell/mm3 (African American Males) or \>= 11,001 cell/mm3 or \<= 2,499 cell/mm3 (African American Females) or \>= 10,001 cell/mm3 or \<= 3,999 cell/mm3 (all others). If a result met the threshold for an AE at baseline, subsequent results were only considered to be an AE if the grading worsened in severity.

  Baseline (Day -1) through Day 21

• Number of Participants With Abnormal Coagulation Laboratory Toxicity Results

  Laboratory parameters include prothrombin time (PT), activated partial prothrombin time (PTT), and prothrombin international normalized ratio (INR). Thresholds for adverse events were considered as PT \>= 11.6 s, PTT \>= 30.1 s, INR \>= 1.2. If a coagulation laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.

  Baseline (Day -1) through Day 21

• Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results

  The only graded urinalysis laboratory parameter was red blood cells (RBC) by complete urinalysis. The threshold for adverse events was considered as \>=3. If a urinalysis laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.

  Baseline (Day -1) through Day 21

• Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results

  Each participant is only counted once per toxicity grade for the worst severity recorded. The only ECG parameter graded was QTcF interval with a threshold of \>= 30 msec. If an ECG value met the threshold for an AE at baseline, subsequent safety ECG results were only considered to be an AE if the grading worsened in severity.

  Day 1 through Day 21

• Number of Participants With Abnormal Vital Signs

  Each participant is only counted once per toxicity grade for the worst severity recorded. Vital sign parameters include systolic blood pressure (BP), diastolic BP, pulse, respiratory rate, and temperature. Thresholds for abnormal vital signs were considered as systolic BP \>= 141 mmHg or \<= 89 mmHg, diastolic BP \>= 91 mmHg, pulse \<= 54 bpm (baseline \> 60 bpm) or \<=50 (baseline \<= 60 bpm) or \>= 101 bpm, respiratory rate \>= 17 breaths per minute, and temperature \>= 38.0 degrees Celsius. If a vital sign result met the threshold for an AE at baseline, subsequent vital sign results were only considered to be an AE if the grading worsened in severity.

  Baseline (Day -1) through Day 21

Secondary Outcomes (16)

• VT-1598 Concentrations in Plasma

  0 hours (h), 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 24 h, 36 h, 48 h, 60 h, 72 h, 144 h, 312 h, and 480 h post dose

• VT-11134 Concentrations in Plasma

  0 h, 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 24 h, 36 h, 48 h, 60 h, 72 h, 144 h, 312 h, and 480 h post dose

• Maximum Observed Concentration (Cmax) of VT-1598 and VT-11134

  0 h through 480 h post dose

• Dose-normalized Maximum Observed Concentration (Cmax/Dose) of VT-1598 and VT-11134

  0 h through 480 h post dose

• Time of Maximum Observed Concentration (Tmax) of VT-1598 and VT-11134

  0 h through 480 h post dose

Study Arms (6)

Cohort 1

EXPERIMENTAL

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; Drug: VT-1598

Cohort 2

EXPERIMENTAL

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; Drug: VT-1598

Cohort 3

EXPERIMENTAL

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; Drug: VT-1598

Cohort 4

EXPERIMENTAL

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; Drug: VT-1598

Cohort 5

EXPERIMENTAL

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; Drug: VT-1598

Cohort 6

EXPERIMENTAL

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; Drug: VT-1598

Interventions

Placebo OTHER

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

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6

VT-1598 DRUG

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

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to provide written informed consent and authorization for use of protected health information.
• 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.
• Male or female subjects, 18 - 45 years of age (inclusive).
• Subject is in good health to be safely enrolled in this protocol as determined by medical history and physical exam.
• Body Mass Index (BMI) of 18 - 35 kg / m\^2, inclusive, and minimum weight of 50 kg.
• 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).
• 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.
• Subject has adequate venous access for blood collection.

You may not qualify if:

• Has a chronic condition that may increase risk to subject or interfere with endpoint assessment (e.g., liver disease, kidney disease, immunodeficiency).
• Chronic condition diagnosed within 90 days of the screening visit.
• 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
• History of psychiatric condition that has required hospitalization in the last 5 years or patient is considered unstable by study investigator.
• Any condition that in the opinion of the Investigator could significantly impact drug absorption, distribution, or elimination.
• 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.
• Abnormal Electrocardiograms (ECGs).
• Electrocardiographic QTcF interval \>430 msec for males and \>450 msec for females at Screening.
• 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).
• Positive urine drug test. The drugs that will be screened for includes amphetamines, barbiturates , cocaine, opiates, cannabinoids, phencyclidine, and benzodiazepines.
• 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.
• Received any study product in a clinical trial within 30 days prior to Screening.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

ICON Early Phase Services Clinical Research Unit

San Antonio, Texas, 78209-1015, United States

Location

MeSH Terms

Conditions

Coccidioidomycosis

Interventions

VT-1598

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Dr. Cassandra Key, Senior Medical Director
• Organization: ICON Early Phase Services, LLC

Cassandra.key@iconplc.com

210-283-4120

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: December 23, 2019
• Study Start: September 29, 2020
• Primary Completion: December 27, 2021
• Study Completion: December 27, 2021
• Last Updated: July 26, 2024
• Results First Posted: January 11, 2023

Record last verified: 2020-01-31

Locations

US (1)