Clinical trial NCT02061358: Study to Determine the Safety, Tolerability and Pharmacokinetics of UV-4B Solution Administered Orally in Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Viral Infection
Keywords: Dengue
Arbovirus Infections
Flaviviridae Infections
Flavivirus Infections
Hemorrhagic Fevers, Viral
RNA Virus Infections
Virus Diseases
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses
Lead sponsor: Emergent BioSolutions
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
name: Unither Virology
First posted: 2014-02-12
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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)

Primary outcomes:
measure: Subjects With Treatment-emergent Adverse Event (TEAEs) by Treatment Group
timeFrame: From time of the first dose administration through Day 9 ± 1
measure: Subjects With Serious Adverse Event (SAEs) by Treatment Group
timeFrame: From time of the first dose administration through Day 9 ± 1
measure: Number of Subjects With Vital Sign Values of Toxicity Grade 1 or Higher Postdose by Treatment Group (Safety Population)
timeFrame: From time of the first dose administration through Day 9 ± 1
measure: Number of Subjects With Electrocardiogram Outlier Values Postdose by Treatment Group
timeFrame: From time of the first dose administration through Day 9 ± 1
measure: Number of Subjects With Clinical Laboratory Test Results of Toxicity Grade 1 or Higher at Day 9 by Treatment Group
timeFrame: Day 9 ± 1
Secondary outcomes:
measure: Cmax by Treatment Group: UV-4
timeFrame: 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)
measure: Tmax by Treatment Group: UV-4
timeFrame: 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)
measure: AUC(0-last) by Treatment Group: UV-4
timeFrame: 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)
measure: AUC(0-inf) by Treatment Group: UV-4
timeFrame: 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)
measure: CL/F by Treatment Group: UV-4
timeFrame: 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)
measure: Vz/F by Treatment Group: UV-4
timeFrame: 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)
measure: t(1/2) by Treatment Group: UV-4
timeFrame: 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)
measure: Interval and Cumulative Amount (mg) of UV-4 Excreted in Urine, Ae, by Treatment Group
timeFrame: 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
measure: Interval and Cumulative Percent of UV-4 Excreted in Urine, fe, by Treatment Group
timeFrame: 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
measure: CLr by Treatment Group: UV-4
timeFrame: 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)
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Quintiles, Inc
state: Kansas
Study officials:
affiliation: Senior Medical Research Director, Quintiles
name: Thomas Murtaugh, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Callahan M, Treston AM, Lin G, Smith M, Kaufman B, Khaliq M, Evans DeWald L, Spurgers K, Warfield KL, Lowe P, Duchars M, Sampath A, Ramstedt U. Randomized single oral dose phase 1 study of safety, tolerability, and pharmacokinetics of Iminosugar UV-4 Hydrochloride (UV-4B) in healthy subjects. PLoS Negl Trop Dis. 2022 Aug 8;16(8):e0010636. doi: 10.1371/journal.pntd.0010636. eCollection 2022 Aug.