NCT02711267

Brief Summary

The overall aim of this clinical study is to investigate the ability of dermal open flow microperfusion to assess bioequivalence and non-bioequivalence of acyclovir formulations in the skin of healthy volunteers.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
36

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jan 2014

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2014

Completed
1.6 years until next milestone

First Submitted

Initial submission to the registry

July 29, 2015

Completed
3 days until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2015

Completed
8 months until next milestone

First Posted

Study publicly available on registry

March 17, 2016

Completed
Last Updated

March 17, 2016

Status Verified

March 1, 2016

Enrollment Period

1.6 years

First QC Date

July 29, 2015

Last Update Submit

March 11, 2016

Conditions

Dermatologic Disorders

Keywords

Open Flow Microperfusion

Outcome Measures

Primary Outcomes (2)

  • AUC

    Area under the dOFM acyclovir concentration curve (AUC) during 12/36h of OFM-Sampling (post-dose)

    during 12-36h of OFM-Sampling (post-dose)

  • CMAX

    Maximum observed dOFM acyclovir concentration (CMAX) during 12/36h of OFM-Sampling (post-dose)

    during 12-36h of OFM-Sampling (post-dose)

Secondary Outcomes (2)

  • dOFM acyclovir concentration

    during 12-36h of OFM-Sampling (post-dose)

  • TMAX

    during 12-36h of OFM-Sampling (post-dose)

Study Arms (4)

Phase 1: Optimization Study

EXPERIMENTAL

6 subjects will be included in this study, each with 3 application sites on the arm and 3 on the leg. 2 dOFM probes (OFM Probe) will be implanted per site resulting in 12 dOFM probes per subject (operated by OFM pump). On each the arm and the leg the proximal and distal site of the 3 adjacent sites will be treated by 5% Zovirax® cream. The central site on arm and leg will be left untreated in order to test a potential lateral carry-over of acyclovir from one application site to the other. Blood samples will be taken to test for uptake into the blood stream and redistribution to other application sites.

Drug: 5% Zovirax® creamProcedure: OFMDevice: OFM ProbeDevice: OFM Pump

Phase 2: Formulation Study

EXPERIMENTAL

6 subjects will be included in this study, each with 3 application sites on the arm and 3 on the leg. 2 dOFM probes will be implanted per site resulting in 12 dOFM probes per subject. Different topical 5% acyclovir formulations currently available on the market will be tested. One application site on the arm and one on the leg will be used for U.S. Zovirax® cream 5% application. The remaining two application sites on the arm and the remaining 2 on the leg will be used to randomly administer two of the remaining formulations (5% Aciclostad cream, 5% Aciclovir cream 1A Pharma, 5% Zovirax® cream (Austria), 5% Zovirax Cold Sore Cream) according to an application pattern.

Drug: 5% Zovirax® creamDrug: 5% Aciclostad creamDrug: 5% Aciclovir cream 1A PharmaDrug: 5% Zovirax Cold Sore CreamDrug: 5% Zovirax® cream (Austria)Procedure: OFMDevice: OFM ProbeDevice: OFM Pump

Phase 3: Pilot BE study

EXPERIMENTAL

4 subjects will be included in the pilot BE study with 3 application sites on each leg. 2 dOFM probes will be implanted per site resulting in 12 dOFM probes per subject. One reference drug product (R) and one test drug product (T) will be applied on the application sites in order to test for BE between duplicate sites with R applied, and to test for non-BE between application sites with R and T applied.

Drug: 5% Zovirax® creamDrug: 5% Aciclovir cream 1A PharmaProcedure: OFMDevice: OFM ProbeDevice: OFM Pump

Phase 4: Main BE Study

EXPERIMENTAL

20 subjects will be included in the pilot BE study with 3 application sites on each leg. 2 dOFM probes will be implanted per site resulting in 12 dOFM probes per subject. One reference drug (R) and one test drug (T) will be applied on the application sites in order to test for BE between duplicate sites with R applied and to test for non-BE between application sites with R and T applied.

Drug: 5% Zovirax® creamDrug: 5% Aciclovir cream 1A PharmaProcedure: OFMDevice: OFM ProbeDevice: OFM Pump

Interventions

5% Zovirax® creamDRUG

(manufactured by GlaxoSmithKline Pharma in Canada, distributed in the USA by Valeant Pharmaceuticals North America LCC, Bridgewater,NJ 08807)

Also known as: Aciclovir
Phase 1: Optimization StudyPhase 2: Formulation StudyPhase 3: Pilot BE studyPhase 4: Main BE Study
5% Aciclostad creamDRUG

(STADA Arzneimittel GmbH, Vienna, Austria)

Also known as: Aciclovir
Phase 2: Formulation Study
5% Aciclovir cream 1A PharmaDRUG

(1A Pharma GmbH, Vienna, Austria)

Also known as: Aciclovir
Phase 2: Formulation StudyPhase 3: Pilot BE studyPhase 4: Main BE Study
5% Zovirax Cold Sore CreamDRUG

(GlaxoSmithKline Consumer Health Care, Brendfort, UK; Marketing authorization holder: Beeham Group PLC, Brendfort, UK)

Also known as: Aciclovir
Phase 2: Formulation Study
5% Zovirax® cream (Austria)DRUG

(GlaxoSmithKline Pharma GmbH, Vienna, Austria)

Also known as: Aciclovir
Phase 2: Formulation Study
OFMPROCEDURE

Sampling method for interstitial fluid

Also known as: Open Flow Microperfusion
Phase 1: Optimization StudyPhase 2: Formulation StudyPhase 3: Pilot BE studyPhase 4: Main BE Study
OFM ProbeDEVICE

Sampling probe used during OFM

Also known as: 'DEA15003' (linear type, 0.5mm OD, 15mm open mesh)
Phase 1: Optimization StudyPhase 2: Formulation StudyPhase 3: Pilot BE studyPhase 4: Main BE Study
OFM PumpDEVICE

Pump used to operate OFM probes

Also known as: 'MPP102' (wearable, operates 3 to 6 probes)
Phase 1: Optimization StudyPhase 2: Formulation StudyPhase 3: Pilot BE studyPhase 4: Main BE Study

Eligibility Criteria

Age21 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Written informed consent must be obtained before any assessment is performed.
  • Male and female subjects 21 to 50 years of age inclusive and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
  • Able to communicate well with the investigator, to understand and comply with the requirements of the study.

You may not qualify if:

  • Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations.
  • History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
  • Use of topical corticosteroids or systemic immunosuppression within the last 3 weeks (for topicals) or 3 months (systemic medication)
  • A history of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening or baseline.
  • PR \> 220 msec
  • QRS complex \> 120 msec
  • Long QT syndrome
  • QTcF \> 430 msec males, \> 450 females
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG (human chorionic gonadotropin) laboratory test (\> 10 mIU/mL).
  • Significant medical problems, including but not limited to the following: uncontrolled hypertension (≥160 systolic /95 diastolic mm Hg), congestive heart failure \[New York Heart Association status of class III or IV\].
  • Screening total WBC count \<3,500cells/µL, or platelets \<140,000cells/µL or neutrophils \<2,000cells/µL or hemoglobin \<12 g/dL / \<13.5g/dL for female / male.
  • Active systemic infections during the last two weeks (exception: common cold) prior to enrollment.
  • A febrile illness within 72 hours, or major dental work within 8 days, prior to first dosing.
  • History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
  • A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Medical University Graz

Graz, Styria, 8036, Austria

Location

MeSH Terms

Conditions

Skin Diseases

Interventions

Acyclovir

Condition Hierarchy (Ancestors)

Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

GuanineHypoxanthinesPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Thomas R Pieber, MD

    Medical University of Graz

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 29, 2015

First Posted

March 17, 2016

Study Start

January 1, 2014

Primary Completion

August 1, 2015

Study Completion

August 1, 2015

Last Updated

March 17, 2016

Record last verified: 2016-03

Locations

AU(1)