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Completed

NCT Number: NCT02061358

Study to Determine the Safety, Tolerability and Pharmacokinetics of UV-4B Solution Administered Orally in Healthy Subjects

The objective is to evaluate the safety and tolerability of a single-ascending oral dose of UV-4B in healthy subjects and to determine pharmacokinetic parameters describing absorption and elimination following a single dose of UV-4B in healthy subjects.

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Key information

Conditions

Viral Infection Arbovirus Infections Dengue Flaviviridae Infections Flavivirus Infections Hemorrhagic Fevers, Viral Infections Mosquito-Borne Diseases RNA Virus Infections Vector Borne Diseases Virus Diseases

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Quintiles, Inc

Overland Park, Kansas, 66211, United States

About this study

The causative agent of dengue fever is Dengue Virus (DENV), a member of the flavivirus genus. There are four DENV serotypes. Infection with one serotype results in lifelong immunity against that serotype, but only limited short-term cross-protection from infection with the other serotypes. Immunity to one serotype has a downside as subsequent infections by other serotypes increase the risk of developing more severe forms of dengue, which includes the most lethal form of the disease, dengue hemorrhagic fever. Traditional epidemiologic and serologic-based estimates suggest a range of 50 to 100 million DENV infections per year distributed over 100 countries. Recent cartographic-based modeling studies suggest that up to 390 million of dengue infections per year, of which 96 million are associated with clinical symptoms.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy subjects
  • Women: non-pregnant, non-lactating; if of childbearing potential, on specified contraception measures during the study period
  • Men: using barrier contraception measures during the study period

Exclusion criteria

  • Health conditions
  • Taking prescription and non-prescription drugs (exceptions: acetaminophen, vitamins, hormonal birth control)

Treatment and study plan

UV-4B 3 mg

Drug

Oral solution, single dose

UV-4B 10 mg

Drug

Oral solution, single dose

UV-4B 30 mg

Drug

Oral solution, single dose

UV-4B 90 mg

Drug

Oral solution, single dose

UV-4B 180 mg

Drug

Oral solution, single dose

UV-4B 360 mg

Drug

Oral solution, single dose

UV-4B 720 mg

Drug

Oral solution, single dose

UV-4B 1000 mg

Drug

Oral solution, single dose

Placebo

Drug

Oral solution, single dose

Primary outcomes

  1. Subjects With Treatment-emergent Adverse Event (TEAEs) by Treatment Group

    Time frame: From time of the first dose administration through Day 9 ± 1

    TEAEs are those AEs occurring only after administration of investigational product

  2. Subjects With Serious Adverse Event (SAEs) by Treatment Group

    Time frame: From time of the first dose administration through Day 9 ± 1

    Subjects with AEs considered serious by the investigator

  3. Number of Subjects With Vital Sign Values of Toxicity Grade 1 or Higher Postdose by Treatment Group (Safety Population)

    Time frame: From time of the first dose administration through Day 9 ± 1

    Number of subjects in a treatment group, who had a vital sign value of toxicity Grade 1 or higher: supine and standing systolic blood pressure (BP), supine and standing diastolic BP, supine and standing pulse rate, respiratory rate, and temperature

  4. Number of Subjects With Electrocardiogram Outlier Values Postdose by Treatment Group

    Time frame: From time of the first dose administration through Day 9 ± 1

    Number of subjects in a treatment group with outlier ECG findings: QTcF (Fridericia's), PR, and QRS intervals

  5. Number of Subjects With Clinical Laboratory Test Results of Toxicity Grade 1 or Higher at Day 9 by Treatment Group

    Time frame: Day 9 ± 1

    Number of subjects with Grade 1 toxicity or higher for hematology, coagulation, chemistry and urinalysis analytes. ULN=upper limit of normal; WBC=white blood cell count.

Secondary outcomes

  1. Cmax by Treatment Group: UV-4

    Time frame: Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose)

    Cmax is the maximum plasma concentration, obtained directly from the observed concentration versus time data.

  2. Tmax by Treatment Group: UV-4

    Time frame: Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose)

    Tmax is the time of maximum concentration observed directly from the observed concentration versus time data.

  3. AUC(0-last) by Treatment Group: UV-4

    Time frame: Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose)

    AUC(0-last) is the area under the concentration-time curve from time zero (pre-dose) to time of last quantifiable concentration, calculated by linear up/log down trapezoidal summation.

  4. AUC(0-inf) by Treatment Group: UV-4

    Time frame: Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose)

    AUC(0-inf) is the area under the concentration-time curve in the sample from pre-dose extrapolated to infinite time, calculated by linear up/log down trapezoidal summation and extrapolated to infinity by addition of the last quantifiable concentration divided by the apparent terminal rate constant: AUC(0-last) - C(last)/λ(z).

  5. CL/F by Treatment Group: UV-4

    Time frame: Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose)

    CL/F is the apparent systematic clearance, calculated as dose (free-base equivalent) divided by AUC(0-inf).

  6. Vz/F by Treatment Group: UV-4

    Time frame: Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose)

    Vz/F is the apparent volume of distribution of UV-4 based on the terminal phase, calculated as dose (free-base equivalent) divided by [λ(z) × AUC(0-inf)].

  7. t(1/2) by Treatment Group: UV-4

    Time frame: Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose)

    t(1/2) is the apparent terminal half-life, determined as ln(2)/λ(z).

  8. Interval and Cumulative Amount (mg) of UV-4 Excreted in Urine, Ae, by Treatment Group

    Time frame: Pooled urine samples were collected at predose (-12 to 0 hour), and from 0 to 6, 6 to 12, 12 to 24, and 24 to 48 hours postdose

    Ae is the by-interval and cumulative amounts of UV-4 drug excreted in urine. Intervals were 0 to 6, 6 to 12, 12 to 24, and 24 to 48 hours postdose. Ae by-interval amounts were calculated as the product of urine volume and urine concentration. Ae(0-last) is the cumulative amount of UV-4 drug excreted in urine over the entire collection period, 48 hours. Cumulative amounts were calculated as the summation of the amounts excreted in collection intervals.

  9. Interval and Cumulative Percent of UV-4 Excreted in Urine, fe, by Treatment Group

    Time frame: Pooled urine samples were collected at predose (-12 to 0 hour), and from 0 to 6, 6 to 12, 12 to 24, and 24 to 48 hours postdose

    fe is the by-interval percentage of UV-4 drug excreted in urine. Intervals were 0 to 6, 6 to 12, 12 to 24, and 24 to 48 hours postdose. fe = Ae/(UV-4B dose x 100). fe(0-12), fe(0-24) and fe(0-last) are the cumulative percentages of UV-4 drug excreted in urine over 24 hours and the entire collection period, respectively.

  10. CLr by Treatment Group: UV-4

    Time frame: Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose)

    CLr is the renal clearance, calculated at Ae(0-last) divided by AUC(0-last).

Sponsors and collaborators

Lead sponsor

Emergent BioSolutions

Industry

Collaborators

  • Quintiles, Inc.
  • Unither Virology

Registry information

Official study title

Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Single-Ascending Dose Study to Determine the Safety, Tolerability and Pharmacokinetics of UV-4B Solution Administered Orally in Healthy Subjects

Acronym: UV

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Feb 12, 2014
Registry last updated
Mar 18, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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