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

This study has been completed.
Sponsor:
Collaborators:
Quintiles, Inc.
Emergent BioSolutions
Information provided by (Responsible Party):
Unither Virology
ClinicalTrials.gov Identifier:
NCT02061358
First received: February 6, 2014
Last updated: July 20, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Viral Infection
Drug: UV-4B 3 mg
Drug: UV-4B 10 mg
Drug: UV-4B 30 mg
Drug: UV-4B 90 mg
Drug: UV-4B 180 mg
Drug: UV-4B 360 mg
Drug: UV-4B 720 mg
Drug: UV-4B 1000 mg
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Unither Virology:

Primary Outcome Measures:
  • Subjects With Treatment-emergent Adverse Event (TEAEs) by Treatment Group [ Time Frame: From time of the first dose administration through Day 9 ± 1 ] [ Designated as safety issue: Yes ]
    TEAEs are those AEs occurring only after administration of investigational product

  • Subjects With Serious Adverse Event (SAEs) by Treatment Group [ Time Frame: From time of the first dose administration through Day 9 ± 1 ] [ Designated as safety issue: Yes ]
    Subjects with AEs considered serious by the investigator

  • 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 ] [ Designated as safety issue: Yes ]
    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

  • Number of Subjects With Electrocardiogram Outlier Values Postdose by Treatment Group [ Time Frame: From time of the first dose administration through Day 9 ± 1 ] [ Designated as safety issue: Yes ]
    Number of subjects in a treatment group with outlier ECG findings: QTcF (Fridericia's), PR, and QRS intervals

  • 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 ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • Cmax by Treatment Group: UV-4 [ Time Frame: Samples were collected through 48 hours postdose ] [ Designated as safety issue: No ]
    Cmax is the maximum plasma concentration, obtained directly from the observed concentration versus time data.

  • Tmax by Treatment Group: UV-4 [ Time Frame: Samples were collected through 48 hours postdose ] [ Designated as safety issue: No ]
    Tmax is the time of maximum concentration observed directly from the observed concentration versus time data.

  • AUC(0-last) by Treatment Group: UV-4 [ Time Frame: Samples were collected through 48 hours postdose ] [ Designated as safety issue: No ]
    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.

  • AUC(0-inf) by Treatment Group: UV-4 [ Time Frame: Samples were collected through 48 hours postdose ] [ Designated as safety issue: No ]
    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).

  • CL/F by Treatment Group: UV-4 [ Time Frame: Samples were collected through 48 hours postdose ] [ Designated as safety issue: No ]
    CL/F is the apparent systematic clearance, calculated as dose (free-base equivalent) divided by AUC(0-inf).

  • Vz/F by Treatment Group: UV-4 [ Time Frame: Samples were collected through 48 hours postdose ] [ Designated as safety issue: No ]
    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)].

  • t(1/2) by Treatment Group: UV-4 [ Time Frame: Samples were collected through 48 hours postdose ] [ Designated as safety issue: No ]
    t(1/2) is the apparent terminal half-life, determined as ln(2)/λ(z).

  • Interval and Cumulative Amount (mg) of UV-4 Excreted in Urine, Ae, by Treatment Group [ Time Frame: Samples were collected through 48 hours postdose ] [ Designated as safety issue: No ]
    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.

  • Interval and Cumulative Percent of UV-4 Excreted in Urine, fe, by Treatment Group [ Time Frame: Samples were collected through 48 hours postdose ] [ Designated as safety issue: No ]
    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.

  • CLr by Treatment Group: UV-4 [ Time Frame: Samples were collected through 48 hours postdose ] [ Designated as safety issue: No ]
    CLr is the renal clearance, calculated at Ae(0-last) divided by AUC(0-last).


Enrollment: 64
Study Start Date: July 2014
Study Completion Date: September 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 - 3 mg UV-4B
Subjects receiving UV-4B 3 mg oral solution or placebo
Drug: UV-4B 3 mg
Oral solution, single dose
Drug: Placebo
Oral solution, single dose
Experimental: Cohort 2 - 10 mg UV-4B
Subjects receiving UV-4B 10 mg oral solution or placebo
Drug: UV-4B 10 mg
Oral solution, single dose
Drug: Placebo
Oral solution, single dose
Experimental: Cohort 3- 30 mg UV-4B
Subjects receiving UV-4B 30 mg oral solution or placebo
Drug: UV-4B 30 mg
Oral solution, single dose
Drug: Placebo
Oral solution, single dose
Experimental: Cohort 4 - 90 mg UV-4B
Subjects receiving UV-4B 90 mg oral solution or placebo
Drug: UV-4B 90 mg
Oral solution, single dose
Drug: Placebo
Oral solution, single dose
Experimental: Cohort 5 - 180 mg UV-4B
Subjects receiving UV-4B 180 mg oral solution or placebo
Drug: UV-4B 180 mg
Oral solution, single dose
Drug: Placebo
Oral solution, single dose
Experimental: Cohort 6 - 360 mg UV-4B
Subjects receiving UV-4B 360 mg oral solution or placebo
Drug: UV-4B 360 mg
Oral solution, single dose
Drug: Placebo
Oral solution, single dose
Experimental: Cohort 7 - 720 mg UV-4B
Subjects receiving UV-4B 720 mg oral solution or placebo
Drug: UV-4B 720 mg
Oral solution, single dose
Drug: Placebo
Oral solution, single dose
Experimental: Cohort 8 - 1000 mg UV-4B
Subjects receiving UV-4B 1000 mg oral solution or placebo
Drug: UV-4B 1000 mg
Oral solution, single dose
Drug: Placebo
Oral solution, single dose

Detailed Description:
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.
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02061358

Locations
United States, Kansas
Quintiles, Inc
Overland Park, Kansas, United States, 66211
Sponsors and Collaborators
Unither Virology
Quintiles, Inc.
Emergent BioSolutions
Investigators
Principal Investigator: Thomas Murtaugh, Dr Senior Medical Research Director, Quintiles
  More Information

Additional Information:
Responsible Party: Unither Virology
ClinicalTrials.gov Identifier: NCT02061358     History of Changes
Other Study ID Numbers: DMID 13-0001  KQA71264  UV-DEN-0001 
Study First Received: February 6, 2014
Results First Received: July 20, 2016
Last Updated: July 20, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Unither Virology:
Dengue
Arbovirus Infections
Flaviviridae Infections
Flavivirus Infections
Hemorrhagic Fevers, Viral
RNA Virus Infections
Virus Diseases
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses

Additional relevant MeSH terms:
Infection
Virus Diseases
Pharmaceutical Solutions

ClinicalTrials.gov processed this record on September 26, 2016