Clinical trial NCT02696291: Safety and Pharmacokinetics of UV-4B Solution Administered Orally as Multiple Ascending Doses to Healthy Subjects
Official title: Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Determine the Safety, Tolerability and Pharmacokinetics of UV-4B Solution Administered Orally in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
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: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2016-03-02
Enrollment: 7
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 purpose of this study is to evaluate the safety and pharmacokinetics of UV-4B oral solution when administered to healthy subjects three times a day (TID) for 7 days.

Detailed description: This is a phase 1, randomized, double-blind, placebo-controlled multiple-ascending dose study to evaluate the safety and pharmacokinetics of UV-4B oral solution when administered to healthy subjects TID for 7 days. Three cohorts of 8 subjects each (6 active, 2 placebo) are planned and up to 2 additional cohorts may be added pending safety review of the initial cohorts. Safety review will occur after each cohort. Safety is evaluated through Day 15 on the basis of adverse event (AE) monitoring, clinical laboratory testing (hematology, serum chemistry, coagulation, urinalysis), vital signs, physical examinations (PE), electrocardiograms (ECG), and fecal occult blood testing. Blood samples are collected at specified intervals up to Day 10 for pharmacokinetic assessment.

Eligibility criteria: Inclusion Criteria:

* Nonsmoking, healthy male or female subject aged 18 to 45 years, inclusive.
* Female subject is not pregnant and not lactating.
* (Female subjects only who are not postmenopausal or sterile) agreement to use hormonal contraception OR intrauterine device PLUS barrier contraception (condom or occlusive cap such as a diaphragm or surgical vault cap) AND spermicidal foam/gel/cream/suppository starting at least 14 days before the first dose and continuing for at least 3 months after the last dose.
* (Male subjects only) agreement to use barrier contraception during sexual intercourse and to also refrain from sperm donation from the first day of dosing until 3 months after the last dose of the study product.
* Body weight within 60 to 90 kg, inclusive, and body mass index between 18 to 32 kg/m², inclusive.
* Agreement to avoid strenuous exercise starting 4 days before the start of dosing through the period of confinement in the clinical unit and for at least 96 hours before the follow-up visits.

Exclusion Criteria:

* History of allergy to drugs in the iminosugar class.
* Treatment with any investigational products or therapies within 30 days (or 5 half-lives, whichever is greater) before the first day of dosing.
* Current or past history of disease/dysfunction of the pulmonary, cardiovascular, endocrine, hematologic, neurological, immune, gastrointestinal genitourinary, or other body system.
* Abnormalities on physical examination suggestive of conditions that may pose an increased risk to the subject; abnormal electrocardiogram results (excluding benign conditions); and Grade 1 or higher abnormalities in vital signs at screening and Grade 2 or higher abnormalities in vital signs at check-in based on a modified version of the FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
* Clinical laboratory tests outside the normal range at screening and Grade 2 or higher at check-in to the clinical unit.
* Creatinine clearance \< 90 mL/min (based on Cockcroft-Gault equation).
* Proteinuria greater than or equal to 1+.
* Any known or expected risk of bleeding.
* Scheduled surgical procedure during study participation.
* History of alcohol and/or drug abuse within 1 year prior to dosing and/or a positive urine drug screen for substances of abuse at screening or check-in. Urine alcohol above 50 mg/dL.
* Plasma or blood donation within 30 days before the first day of dosing or intention to donate within 30 days after the final day of dosing.
* Treatment with any medication, either prescription or nonprescription, including dietary supplements or herbal medications, within 14 days before dosing (within 30 days before dosing for hepatic or renal clearance-altering agents) and is unable to refrain from any medication during the study period. Exceptions are acetaminophen (not more than 2 g/day), vitamin products at recommended daily doses or hormonal birth control.
* Positive serology test for HIV antibodies, hepatitis B surface antigen, or hepatitis C virus antibody at screening.
* History of relevant food allergies (ie, eggs or other components of standard clinic meals) or unwilling to comply with diet restrictions.
* Psychological and/or emotional problems which would render the informed consent invalid, or limit the ability of the subject to comply with the study requirements;
* Concurrent enrollment in any other clinical trial within 30 days.

Primary outcomes:
measure: Number of Subjects Reporting Treatment-emergent Adverse Events (TEAEs) by Group
timeFrame: From the time of first dosing on Day 1 through the Day 15 final follow-up visit
measure: Number of Subjects Reporting Serious Adverse Events (SAEs) by Group
timeFrame: From the time of first dosing on Day 1 through the Day 15 final follow-up visit
measure: Number of Subjects With Clinical Laboratory Abnormalities of Toxicity Grade 1 or Higher by Group
timeFrame: From the time of first dosing on Day 1 through the Day 15 final follow-up visit
Secondary outcomes:
measure: Number of Subjects With Outlying Vital Sign Results by Group
timeFrame: From the time of first dosing on Day 1 through the Day 15 final follow-up visit
measure: Number of Subjects With 12-lead Electrocardiogram (ECG) Abnormalities Postdose by Group
timeFrame: From the time of first dosing on Day 1 through the Day 15 final follow-up visit
measure: Maximum Plasma Concentration (Cmax)
timeFrame: Day 1, Day 7
measure: Time of Maximum Plasma Concentration (Tmax)
timeFrame: Day 1, Day 7
measure: Area Under the Concentration-time Curve From Time Zero (Predose) to Time of the Last Quantifiable Concentration After the Last Dose [AUC(0-last)]
timeFrame: Day 7
measure: Total Daily Exposure at Steady State: Area Under the Concentration-time Curve From Time Zero (Predose) Until 24 Hours After the Last Dose [AUC(0-24)]
timeFrame: Day 7
measure: Area Under the Concentration-time Curve From Time Zero (Predose) Until 8 Hours After the Final Dose [AUC(0-8)]
timeFrame: Day 1, Day 7
measure: Apparent Systemic Clearance (CL/F) at Steady State
timeFrame: Day 7
measure: Apparent Volume of Distribution of UV-4 During the Terminal Phase (Vz/F) After Multiple Doses
timeFrame: Day 7
measure: Apparent Terminal Half Life (t1/2)
timeFrame: Day 7
measure: Accumulation Ratio (AR)
timeFrame: Day 7
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Clinical Research Unit
state: Texas
city: Madison
country: United States
facility: Clinical Research Unit
state: Wisconsin
Study officials:
affiliation: Emergent BioSolutions
name: Timothy Babinchak, MD
role: STUDY_DIRECTOR
References: