Phase 1
Completed N=48
Safety and Pharmacokinetics of VT-1598
Source: ClinicalTrials.gov NCT04208321 ↗Enrolled (actual)
48
Serious AEs
0.0%
Results posted
Jan 2023
Primary outcomePrimary: Number of Participants With Unsolicited Adverse Events — 0; 0; 0; 0 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Unsolicited Adverse Events |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal Chemistry Laboratory Toxicity Results |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal Hematology Laboratory Toxicity Results |
1; 1; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal Coagulation Laboratory Toxicity Results |
0; 0; 1; 2; 0; 1 | — |
| PRIMARY Number of Participants With Abnormal Urinalysis Laboratory Toxicity Results |
1; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal Electrocardiogram (ECG) Toxicity Results |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal Vital Signs |
2; 1; 0; 0; 0; 0 | — |
| SECONDARY VT-1598 Concentrations in Plasma |
0.000; 0.000; 0.000; 0.000; 0.000; 0.000 | — |
| SECONDARY VT-11134 Concentrations in Plasma |
0.000; 0.000; 0.000; 0.000; 0.000; 0.000 | — |
| SECONDARY Maximum Observed Concentration (Cmax) of VT-1598 and VT-11134 |
35.43; 63.93; 108.1; 351.0; 222.2; 322.3 | — |
| SECONDARY Dose-normalized Maximum Observed Concentration (Cmax/Dose) of VT-1598 and VT-11134 |
0.8858; 0.7992; 0.6756; 2.194; 0.6943; 0.5036 | — |
| SECONDARY Time of Maximum Observed Concentration (Tmax) of VT-1598 and VT-11134 |
5.00; 5.00; 4.83; 8.17; 5.05; 4.83 | — |
| SECONDARY Terminal Elimination Half-life (t 1/2) of VT-1598 and VT-11134 |
5.403; 29.07; 17.11; 61.38; 40.70; 33.57 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to the Last Concentration Above the Lower Limit of Quantification (AUC(0-last)) of VT-1598 and VT-11134 |
214.2; 894.3; 1540; 6293; 4177; 7730 | — |
| SECONDARY Dose-normalized Area Under the Concentration-time Curve From Time Zero to the Last Concentration Above the Lower Limit of Quantification (AUC(0-last)) of VT-1598 and VT-11134 |
5.354; 11.18; 9.623; 39.33; 13.05; 12.08 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to Infinity (AUC(0-inf)) of VT-1598 and VT-11134 |
5445; 2797; 1960; 3005; 6923; 6260 | — |
| SECONDARY Dose-normalized Area Under the Concentration-time Curve From Time Zero to Infinity (AUC(0-inf)) of VT-1598 and VT-11134 |
17.02; 4.370; 49.00; 18.78; 43.27; 19.56 | — |
| SECONDARY Apparent First-order Elimination Rate Constant (Lambda Z) of VT-1598 and VT-11134 |
0.01940; 0.06553; 0.005900; 0.006863; 0.005457; 0.005520 | — |
| SECONDARY Apparent Oral Clearance (CL/F) of VT-1598 and VT-11134 |
66.6; 235; 20.4; 56.6; 23.5; 51.5 | — |
| SECONDARY Apparent Volume of Distribution During Terminal Phase (Vd/F) of VT-1598 and VT-11134 |
3440; 4200; 3460; 8230; 4450; 9410 | — |
| SECONDARY Cumulative Amount of VT-1598 and VT-11134 Excreted Into Urine From Time Zero to the Time of the Last Quantifiable Concentration (Ae Last) |
0.0000; 0.0000; 0.0000; 0.0000; 0.0000; 0.0000 | — |
| SECONDARY Percent of VT-1598 Excreted Into Urine (Ae%Dose) |
0.0000; 0.0000; 0.0000; 0.0000; 0.0000; 0.0000 | — |
| SECONDARY Renal Clearance (CLr) of VT-1598 and VT-11134 |
0.000; 0.000; 0.000; 0.000; 0.000; 0.000 | — |
Eligibility Criteria
Inclusion Criteria
- 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.
Exclusion Criteria
- 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.
- Admitted or documented illicit drug use or alcohol abuse within 6 months prior to Screening or during their participation in the trial.
- Consumed alc
Data sourced from ClinicalTrials.gov (NCT04208321). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.