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

Viral Infection Clinical Trial

— UV  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02061358
• Other study ID #: DMID 13-0001
• Secondary ID: KQA71264UV-DEN-0
• Status: Completed
• Phase: Phase 1
• Start date: July 2014
• Est. completion date: September 2015

Study information

• Verified date: March 2024
• Source: Emergent BioSolutions
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: September 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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)

Related Conditions & MeSH terms

• Infections
• Viral Infection
• Virus Diseases

Intervention

Drug:
• UV-4B 3 mg
Oral solution, single dose
• UV-4B 10 mg
Oral solution, single dose
• UV-4B 30 mg
Oral solution, single dose
• UV-4B 90 mg
Oral solution, single dose
• UV-4B 180 mg
Oral solution, single dose
• UV-4B 360 mg
Oral solution, single dose
• UV-4B 720 mg
Oral solution, single dose
• UV-4B 1000 mg
Oral solution, single dose
• Placebo
Oral solution, single dose

Locations

Country	Name	City	State
United States	Quintiles, Inc	Overland Park	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
Emergent BioSolutions	Quintiles, Inc., Unither Virology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subjects With Treatment-emergent Adverse Event (TEAEs) by Treatment Group	TEAEs are those AEs occurring only after administration of investigational product	From time of the first dose administration through Day 9 ± 1
Primary	Subjects With Serious Adverse Event (SAEs) by Treatment Group	Subjects with AEs considered serious by the investigator	From time of the first dose administration through Day 9 ± 1
Primary	Number of Subjects With Vital Sign Values of Toxicity Grade 1 or Higher Postdose by Treatment Group (Safety Population)	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	From time of the first dose administration through Day 9 ± 1
Primary	Number of Subjects With Electrocardiogram Outlier Values Postdose by Treatment Group	Number of subjects in a treatment group with outlier ECG findings: QTcF (Fridericia's), PR, and QRS intervals	From time of the first dose administration through Day 9 ± 1
Primary	Number of Subjects With Clinical Laboratory Test Results of Toxicity Grade 1 or Higher at Day 9 by Treatment Group	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.	Day 9 ± 1
Secondary	Cmax by Treatment Group: UV-4	Cmax is the maximum plasma concentration, obtained directly from the observed concentration versus time data.	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)
Secondary	Tmax by Treatment Group: UV-4	Tmax is the time of maximum concentration observed directly from the observed concentration versus time data.	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)
Secondary	AUC(0-last) by Treatment Group: UV-4	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.	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)
Secondary	AUC(0-inf) by Treatment Group: UV-4	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)/?(z).	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)
Secondary	CL/F by Treatment Group: UV-4	CL/F is the apparent systematic clearance, calculated as dose (free-base equivalent) divided by AUC(0-inf).	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)
Secondary	Vz/F by Treatment Group: UV-4	Vz/F is the apparent volume of distribution of UV-4 based on the terminal phase, calculated as dose (free-base equivalent) divided by [?(z) × AUC(0-inf)].	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)
Secondary	t(1/2) by Treatment Group: UV-4	t(1/2) is the apparent terminal half-life, determined as ln(2)/?(z).	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)
Secondary	Interval and Cumulative Amount (mg) of UV-4 Excreted in Urine, Ae, by Treatment Group	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.	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
Secondary	Interval and Cumulative Percent of UV-4 Excreted in Urine, fe, by Treatment Group	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.	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
Secondary	CLr by Treatment Group: UV-4	CLr is the renal clearance, calculated at Ae(0-last) divided by AUC(0-last).	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)

External Links

•   Information on dengue fever