Safety and Pharmacokinetics of UV-4B Solution Administered Orally as Multiple Ascending Doses to Healthy Subjects

Emergent BioSolutions

Status and phase: Terminated; Phase 1

Conditions: Viral Infection

Treatments: Drug: UV-4B 30 mg oral solution; Drug: UV-4B X mg (dose to be determined) oral solution; Drug: UV-4B 150 mg oral solution; Drug: UV-4B Y mg (dose to be determined) oral solution; Drug: Placebo; Drug: UV-4B 75 mg oral solution

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT02696291

DMID 15-0062

8311-270 (Other Identifier)

HHSN272201100030C (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 7 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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7 participants in 5 patient groups

Cohort 1 - 30 mg

Experimental group

Description:

Subjects receiving UV-4B 30 mg oral solution or placebo

Treatment:

Drug: Placebo

Drug: UV-4B 30 mg oral solution

Cohort 2 - 75 mg

Experimental group

Description:

Subjects receiving UV-4B 75 mg oral solution or placebo

Treatment:

Drug: UV-4B 75 mg oral solution

Drug: Placebo

Cohort 3 - 150 mg

Experimental group

Description:

Subjects receiving UV-4B 150 mg oral solution or placebo

Treatment:

Drug: Placebo

Drug: UV-4B 150 mg oral solution

Cohort 4 - X mg (dose to be determined)

Experimental group

Description:

Subjects receiving UV-4B X mg (dose to be determined) oral solution or placebo

Treatment:

Drug: Placebo

Drug: UV-4B X mg (dose to be determined) oral solution

Cohort 5 - Y mg (dose to be determined)

Experimental group

Description:

Subjects receiving UV-4B Y mg (dose to be determined) oral solution or placebo

Treatment:

Drug: UV-4B Y mg (dose to be determined) oral solution

Drug: Placebo