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

NCT02696291 | Terminated Phase 1 Results DMC

• 3 other identifiers: DMID 15-0062HHSN272201100030C8311-270
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (3)

• Number of Subjects Reporting Treatment-emergent Adverse Events (TEAEs) by Group

  The incidence of TEAEs spontaneously reported by subjects or elicited during examination is reported by dose group. Subjects having multiple TEAEs are counted only once.

  From the time of first dosing on Day 1 through the Day 15 final follow-up visit

• Number of Subjects Reporting Serious Adverse Events (SAEs) by Group

  The incidence of SAEs spontaneously reported by subjects or elicited during examination is reported by dose group. Subjects having multiple SAEs are counted only once.

  From the time of first dosing on Day 1 through the Day 15 final follow-up visit

• Number of Subjects With Clinical Laboratory Abnormalities of Toxicity Grade 1 or Higher by Group

  Clinical laboratory abnormalities are presented as the total of Grade 1 (mild) through Grade 4 (potentially life-threatening) abnormalities according to criteria adapted from the Food and Drug Administration (FDA) Guidance for Industry, Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (September 2007) and the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table (November 2007). Within each parameter, subjects having multiple abnormalities are counted only once.

  From the time of first dosing on Day 1 through the Day 15 final follow-up visit

Secondary Outcomes (11)

• Number of Subjects With Outlying Vital Sign Results by Group

  From the time of first dosing on Day 1 through the Day 15 final follow-up visit

• Number of Subjects With 12-lead Electrocardiogram (ECG) Abnormalities Postdose by Group

  From the time of first dosing on Day 1 through the Day 15 final follow-up visit

• Maximum Plasma Concentration (Cmax)

  Day 1, Day 7

• Time of Maximum Plasma Concentration (Tmax)

  Day 1, Day 7

• Area Under the Concentration-time Curve From Time Zero (Predose) to Time of the Last Quantifiable Concentration After the Last Dose [AUC(0-last)]

  Day 7

Study Arms (5)

Cohort 1 - 30 mg

EXPERIMENTAL

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

Drug: UV-4B 30 mg oral solution; Drug: Placebo

Cohort 2 - 75 mg

EXPERIMENTAL

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

Drug: UV-4B 75 mg oral solution; Drug: Placebo

Cohort 3 - 150 mg

EXPERIMENTAL

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

Drug: UV-4B 150 mg oral solution; Drug: Placebo

Cohort 4 - X mg (dose to be determined)

EXPERIMENTAL

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

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

Cohort 5 - Y mg (dose to be determined)

EXPERIMENTAL

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

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

Interventions

UV-4B 30 mg oral solution DRUG

UV-4B 30 mg oral solution administered TID (every 8 ± 0.5 hours) for 7 days

Cohort 1 - 30 mg

UV-4B 75 mg oral solution DRUG

UV-4B 75 mg oral solution administered TID (every 8 ± 0.5 hours) for 7 days

Cohort 2 - 75 mg

UV-4B 150 mg oral solution DRUG

UV-4B 150 mg oral solution administered TID (every 8 ± 0.5 hours) for 7 days

Cohort 3 - 150 mg

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

UV-4B X mg (dose to be determined) oral solution administered TID (every 8 ± 0.5 hours) for 7 days

Cohort 4 - X mg (dose to be determined)

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

UV-4B Y mg (dose to be determined) oral solution administered TID (every 8 ± 0.5 hours) for 7 days

Cohort 5 - Y mg (dose to be determined)

Placebo DRUG

Placebo oral solution administered TID (every 8 ± 0.5 hours) for 7 days

Cohort 1 - 30 mg; Cohort 2 - 75 mg; Cohort 3 - 150 mg; Cohort 4 - X mg (dose to be determined); Cohort 5 - Y mg (dose to be determined)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Emergent BioSolutions: lead

Study Sites (2)

Clinical Research Unit

Dallas, Texas, 75247, United States

Location

Clinical Research Unit

Madison, Wisconsin, 53704, United States

Location

Related Links

• For information on dengue fever

MeSH Terms

Conditions

Virus Diseases; Dengue; Arbovirus Infections; Flaviviridae Infections; Flavivirus Infections; Hemorrhagic Fevers, Viral; RNA Virus Infections

Interventions

Solutions

Condition Hierarchy (Ancestors)

Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Limitations and Caveats

Study was terminated after Cohort 1. While no analysis was performed for change from baseline for physical exam (PE, a secondary endpoint), any change from baseline PE was reported/analyzed as an AE. AUC0-inf (secondary endpoint) was not calculated.

Results Point of Contact

• Title: Tim Babinchak, MD
• Organization: Emergent Product Development Gaithersburg, Inc.

tbabinchak@ebsi.com

(240) 631-3585

Study Officials

• Timothy Babinchak, MD

  Emergent BioSolutions

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2016
• First Posted: March 2, 2016
• Study Start: May 27, 2016
• Primary Completion: March 2, 2017
• Study Completion: March 2, 2017
• Last Updated: March 18, 2024
• Results First Posted: March 16, 2018

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)