Study to Determine the Safety, Tolerability and Pharmacok... | NCT02061358 | Trialant
NCT02061358
Sponsor
Emergent BioSolutions
Status
Completed
Last Update Posted
Mar 18, 2024Actual
Enrollment
64Actual
Phase
Phase 1
Conditions
Viral Infection
Interventions
UV-4B 3 mg
UV-4B 10 mg
UV-4B 30 mg
UV-4B 90 mg
UV-4B 180 mg
UV-4B 360 mg
UV-4B 720 mg
UV-4B 1000 mg
Placebo
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT02061358
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
DMID 13-0001
Secondary IDs
ID
Type
Description
Link
KQA71264
UV-DEN-0001
Brief Title
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
Acronym
UV
Organization
Emergent BioSolutionsINDUSTRY
Status Module
Record Verification Date
Mar 2024
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jul 2014
Primary Completion Date
Jul 2015Actual
Completion Date
Sep 2015Actual
First Submitted Date
Feb 6, 2014
First Submission Date that Met QC Criteria
Feb 11, 2014
First Posted Date
Feb 12, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Jul 20, 2016
Results First Submitted that Met QC Criteria
Jul 20, 2016
Results First Posted Date
Sep 1, 2016Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Mar 14, 2024
Last Update Posted Date
Mar 18, 2024Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Emergent BioSolutionsINDUSTRY
Collaborators
Name
Class
Quintiles, Inc.
INDUSTRY
Unither Virology
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Conditions Module
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
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
64Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cohort 1 - 3 mg UV-4B
Experimental
Subjects receiving UV-4B 3 mg oral solution or placebo
Drug: UV-4B 3 mg
Drug: Placebo
Cohort 2 - 10 mg UV-4B
Experimental
Subjects receiving UV-4B 10 mg oral solution or placebo
Drug: UV-4B 10 mg
Drug: Placebo
Cohort 3- 30 mg UV-4B
Experimental
Subjects receiving UV-4B 30 mg oral solution or placebo
Drug: UV-4B 30 mg
Drug: Placebo
Cohort 4 - 90 mg UV-4B
Experimental
Subjects receiving UV-4B 90 mg oral solution or placebo
Drug: UV-4B 90 mg
Drug: Placebo
Cohort 5 - 180 mg UV-4B
Experimental
Subjects receiving UV-4B 180 mg oral solution or placebo
Drug: UV-4B 180 mg
Drug: Placebo
Cohort 6 - 360 mg UV-4B
Experimental
Interventions
Name
Type
Description
Arm Group Labels
Other Names
UV-4B 3 mg
Drug
Oral solution, single dose
Cohort 1 - 3 mg UV-4B
UV-4B 10 mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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
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
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
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
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 Outcomes
Measure
Description
Time Frame
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)
Tmax by Treatment Group: UV-4
Other Outcomes
Not provided
Eligibility Module
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
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.
Each cohort was assigned 6 subjects who received the cohort's prescribed dose of UV-4B, along with 2 subjects in each cohort assigned to receive placebo.
Recruitment Details
This was a single center study performed in the United States. The study was completed with a total of 64 patients enrolled.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
FG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Subjects receiving UV-4B 360 mg oral solution or placebo
Drug: UV-4B 360 mg
Drug: Placebo
Cohort 7 - 720 mg UV-4B
Experimental
Subjects receiving UV-4B 720 mg oral solution or placebo
Drug: UV-4B 720 mg
Drug: Placebo
Cohort 8 - 1000 mg UV-4B
Experimental
Subjects receiving UV-4B 1000 mg oral solution or placebo
Drug: UV-4B 1000 mg
Drug: Placebo
Drug
Oral solution, single dose
Cohort 2 - 10 mg UV-4B
UV-4B 30 mg
Drug
Oral solution, single dose
Cohort 3- 30 mg UV-4B
UV-4B 90 mg
Drug
Oral solution, single dose
Cohort 4 - 90 mg UV-4B
UV-4B 180 mg
Drug
Oral solution, single dose
Cohort 5 - 180 mg UV-4B
UV-4B 360 mg
Drug
Oral solution, single dose
Cohort 6 - 360 mg UV-4B
UV-4B 720 mg
Drug
Oral solution, single dose
Cohort 7 - 720 mg UV-4B
UV-4B 1000 mg
Drug
Oral solution, single dose
Cohort 8 - 1000 mg UV-4B
Placebo
Drug
Oral solution, single dose
Cohort 1 - 3 mg UV-4B
Cohort 2 - 10 mg UV-4B
Cohort 3- 30 mg UV-4B
Cohort 4 - 90 mg UV-4B
Cohort 5 - 180 mg UV-4B
Cohort 6 - 360 mg UV-4B
Cohort 7 - 720 mg UV-4B
Cohort 8 - 1000 mg UV-4B
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)
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)
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)/λ(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)
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)
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 [λ(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)
t(1/2) by Treatment Group: UV-4
t(1/2) is the apparent terminal half-life, determined as ln(2)/λ(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)
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
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
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)
FG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
FG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
FG004
180 mg UV-4B
UV-4B 180 mg oral, single dose
FG005
360 mg UV-4B
UV-4B 360 mg oral, single dose
FG006
720 mg UV-4B
UV-4B 720 mg oral, single dose
FG007
1000 mg UV-4B
UV-4B 1000 mg oral, single dose
FG008
Placebo
Placebo oral, single dose
FG0006 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG0046 subjects
FG0056 subjects
FG0066 subjects
FG0076 subjects
FG00816 subjects
COMPLETED
FG0006 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG0046 subjects
FG0056 subjects
FG0066 subjects
FG0076 subjects
FG00816 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
Total number of randomized subjects in each cohort
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
BG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
BG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
BG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
BG004
180 mg UV-4B
UV-4B 180 mg oral, single dose
BG005
360 mg UV-4B
UV-4B 360 mg oral, single dose
BG006
720 mg UV-4B
UV-4B 720 mg oral, single dose
BG007
1000 mg UV-4B
UV-4B 1000 mg oral, single dose
BG008
Placebo
Placebo oral, single dose
BG009
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0006
BG0016
BG0026
BG0036
BG0046
BG0056
BG0066
BG0076
BG00816
BG00964
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00025± 5
BG00127± 8
BG00227± 4
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0003
BG0012
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0001
BG0011
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0011
BG002
Height
Mean
Standard Deviation
cm
Title
Denominators
Categories
Title
Measurements
BG000173.4± 11.1
BG001171.8± 12.3
BG002
Weight
Mean
Standard Deviation
kg
Title
Denominators
Categories
Title
Measurements
BG00082.9± 12.1
BG00179.6± 13.8
BG002
Body mass index
Mean
Standard Deviation
kg/m^2
Title
Denominators
Categories
Title
Measurements
BG00027.44± 1.28
BG00126.88± 2.6
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Subjects With Treatment-emergent Adverse Event (TEAEs) by Treatment Group
TEAEs are those AEs occurring only after administration of investigational product
Safety Population: all subjects who received any investigational product, UV-4B or placebo
Posted
Number
Subjects with at least 1 TEAE
From time of the first dose administration through Day 9 ± 1
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
OG004
180 mg UV-4B
UV-4B 180 mg oral, single dose
OG005
360 mg UV-4B
UV-4B 360 mg oral, single dose
OG006
720 mg UV-4B
UV-4B 720 mg oral, single dose
OG007
1000 mg UV-4B
UV-4B 1000 mg oral, single dose
OG008
Placebo
Placebo oral, single dose
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0005
OG0016
OG0025
OG003
Primary
Subjects With Serious Adverse Event (SAEs) by Treatment Group
Subjects with AEs considered serious by the investigator
Safety Population: all subjects who received any investigational product, UV-4B or placebo
Posted
Number
Subjects with at least 1 SAE
From time of the first dose administration through Day 9 ± 1
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
OG004
180 mg UV-4B
UV-4B 180 mg oral, single dose
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
Safety Population: all subjects who received any investigational product, UV-4B or placebo
Posted
Number
Participants
From time of the first dose administration through Day 9 ± 1
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
OG004
180 mg UV-4B
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
Safety Population: all subjects who received any investigational product, UV-4B or placebo
Posted
Number
participants
From time of the first dose administration through Day 9 ± 1
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
OG004
180 mg UV-4B
UV-4B 180 mg oral, single dose
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.
Safety Population: all subjects who received any investigational product, UV-4B or placebo
Posted
Number
Participants
Day 9 ± 1
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
OG004
180 mg UV-4B
UV-4B 180 mg oral, single dose
Secondary
Cmax by Treatment Group: UV-4
Cmax is the maximum plasma concentration, obtained directly from the observed concentration versus time data.
The pharmacokinetic (PK) population consisted of all subjects who received active investigational product, UV-4B, and had at least 1 measured concentration at a scheduled PK time after start of dosing for UV-4B.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
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)
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
OG004
Secondary
Tmax by Treatment Group: UV-4
Tmax is the time of maximum concentration observed directly from the observed concentration versus time data.
The pharmacokinetic (PK) population consisted of all subjects who received active investigational product, UV-4B, and had at least 1 measured concentration at a scheduled PK time after start of dosing for UV-4B.
Posted
Median
Full Range
hours
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)
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
OG004
180 mg UV-4B
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.
The pharmacokinetic (PK) population consisted of all subjects who received active investigational product, UV-4B, and had at least 1 measured concentration at a scheduled PK time after start of dosing for UV-4B.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng * h/mL
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)
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
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)/λ(z).
The pharmacokinetic (PK) population consisted of all subjects who received active investigational product, UV-4B, and had at least 1 measured concentration at a scheduled PK time after start of dosing for UV-4B. Subjects in this population were used for all PK summaries.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng * h/mL
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)
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
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).
The pharmacokinetic (PK) population consisted of all subjects who received active investigational product, UV-4B, and had at least 1 measured concentration at a scheduled PK time after start of dosing for UV-4B.
Posted
Geometric Mean
Geometric Coefficient of Variation
L/h
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)
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
OG004
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 [λ(z) × AUC(0-inf)].
The pharmacokinetic (PK) population consisted of all subjects who received active investigational product, UV-4B, and had at least 1 measured concentration at a scheduled PK time after start of dosing for UV-4B.
Posted
Geometric Mean
Geometric Coefficient of Variation
L
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)
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
Secondary
t(1/2) by Treatment Group: UV-4
t(1/2) is the apparent terminal half-life, determined as ln(2)/λ(z).
The pharmacokinetic (PK) population consisted of all subjects who received active investigational product, UV-4B, and had at least 1 measured concentration at a scheduled PK time after start of dosing for UV-4B.
Posted
Median
Full Range
hours
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)
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
OG004
180 mg UV-4B
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.
The pharmacokinetic (PK) population consisted of all subjects who received active investigational product, UV-4B, and had at least 1 measured concentration at a scheduled PK time after start of dosing for UV-4B. Subjects in this population were used for all PK summaries.
Posted
Mean
Standard Deviation
mg
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
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
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.
The pharmacokinetic (PK) population consisted of all subjects who received active investigational product, UV-4B, and had at least 1 measured concentration at a scheduled PK time after start of dosing for UV-4B.
Posted
Mean
Standard Deviation
percentage of dose
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
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
Secondary
CLr by Treatment Group: UV-4
CLr is the renal clearance, calculated at Ae(0-last) divided by AUC(0-last).
The pharmacokinetic (PK) population consisted of all subjects who received active investigational product, UV-4B, and had at least 1 measured concentration at a scheduled PK time after start of dosing.L/h
Posted
Geometric Mean
Geometric Coefficient of Variation
L/h
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)
ID
Title
Description
OG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
OG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
OG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
OG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
OG004
180 mg UV-4B
Time Frame
From time of the first dose administration through 9 ± 1 days after dosing
Description
Adverse events were coded by the Medical Dictionary for Regulatory Activities (MedDRA) according to system organ class (SOC) and preferred term (PT).
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
3 mg UV-4B
UV-4B 3 mg oral, single dose
0
6
5
6
EG001
10 mg UV-4B
UV-4B 10 mg oral, single dose
0
6
6
6
EG002
30 mg UV-4B
UV-4B 30 mg oral, single dose
0
6
5
6
EG003
90 mg UV-4B
UV-4B 90 mg oral, single dose
0
6
6
6
EG004
180 mg UV-4B
UV-4B 180 mg oral, single dose
0
6
6
6
EG005
360 mg UV-4B
UV-4B 360 mg oral, single dose
0
6
5
6
EG006
720 mg UV-4B
UV-4B 720 mg oral, single dose
0
6
6
6
EG007
1000 mg UV-4B
UV-4B 1000 mg oral, single dose
0
6
5
6
EG008
Placebo
Placebo oral, single dose
0
16
12
16
Serious Adverse Events
Not provided
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Eosinophilia
Blood and lymphatic system disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected16 at risk
Lymphopenia
Blood and lymphatic system disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Bradycardia
Cardiac disorders
MedDRA 16.1
Systematic Assessment
EG0001 events1 affected6 at risk
EG0013 events2 affected6 at risk
EG0022 events2 affected6 at risk
EG003
Supraventricular tachycardia
Cardiac disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0013 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Local swelling
General disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Vessel puncture site bruise
General disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Arthropod sting
Injury, poisoning and procedural complications
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Chemical eye injury
Injury, poisoning and procedural complications
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
APTT prolonged
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0013 events3 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ALT increased
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
AST increased
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood calcium decreased
Investigations
MedDRA 16.1
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood pressure decreased
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood urea increased
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Haemoglobin decreased
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Heart rate decreased
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Lipase increased
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Protein total decreased
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Prothrombin time prolonged
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0012 events2 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Respiratory rate increased
Investigations
MedDRA 16.1
Systematic Assessment
EG0003 events3 affected6 at risk
EG0014 events4 affected6 at risk
EG0021 events1 affected6 at risk
EG003
WBC decreased
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
WBC increased
Investigations
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypokaelemia
Metabolism and nutrition disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypomagnaesemia
Metabolism and nutrition disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypophosphaetemia
Metabolism and nutrition disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypoproteinaemia
Metabolism and nutrition disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Balance disorder
Nervous system disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dizziness postural
Nervous system disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Headache
Nervous system disorders
MedDRA 16.1
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Presyncope
Nervous system disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Tension headache
Nervous system disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA 16.1
Systematic Assessment
EG0002 events2 affected6 at risk
EG0011 events1 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Tachypnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hot flush
Vascular disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Ventricular tachycardia
Cardiac disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Vessel puncture site pain
General disorders
MedDRA 16.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The Sponsor will make the results of the study publicly available, including for purposes of national and international registration, publication, and information for medical and pharmaceutical professionals.