Study to Determine the Safety, Tolerability and Pharmacokinetics of UV-4B Solution Administered Orally in Healthy Subjects

NCT02061358 | Completed Phase 1 Results DMC

• 3 other identifiers: DMID 13-0001KQA71264UV-DEN-0001
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

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 (5)

• 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 (10)

• Cmax by Treatment Group: UV-4

  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

  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

  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

  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

  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)

Study Arms (8)

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

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

Interventions

UV-4B 3 mg DRUG

Oral solution, single dose

Cohort 1 - 3 mg UV-4B

UV-4B 10 mg 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

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• Health conditions
• Taking prescription and non-prescription drugs (exceptions: acetaminophen, vitamins, hormonal birth control)

Sponsors & Collaborators

• Emergent BioSolutions: lead
• Quintiles, Inc.: collaborator
• Unither Virology: collaborator

Study Sites (1)

Quintiles, Inc

Overland Park, Kansas, 66211, United States

Location

Related Publications (1)

• 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.

  PMID: 35939501 DERIVED

Related Links

• Information on dengue fever

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Clinical Development Representative
• Organization: Emergent BioSolutions

ctgov@ebsi.com

Study Officials

• Thomas Murtaugh, Dr

  Senior Medical Research Director, Quintiles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: February 6, 2014
• First Posted: February 12, 2014
• Study Start: July 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: September 1, 2015
• Last Updated: March 18, 2024
• Results First Posted: September 1, 2016

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)