Clinical trial NCT02711267: Bioequivalence of Topical Acyclovir in Healthy Volunteers
Official title: An Exploratory Study to Evaluate Dermal Open Flow Microperfusion's (dOFM) Ability to Assess Bioequivalence and Non-bioequivalence of Topical Acyclovir Formulations in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dermatologic Disorders
Keywords: Open Flow Microperfusion
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: Joanneum Research Forschungsgesellschaft mbH
First posted: 2016-03-17
Enrollment: 36
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

Detailed description: This will be a single center, open label, exploratory research study to evaluate the BE of already marketed formulations of acyclovir in dermal interstitial fluid (ISF) in healthy volunteers using dOFM. The study will be conducted at the Clinical Research Center at the Medical University Graz. dOFM represents the most reliable way to sample interstitial fluid from skin, since it provides diluted but otherwise unchanged dermal interstitial fluid. To assess BE and non-BE, we have designed the experiments in such a way that each subject can serve as its own control. Each subject will have two sets of BE and non-BE pairs in parallel. This study is designed to test dOFM, a new sampling method that allows measurement of skin penetration. Measurement of skin penetration enables the reduction of the impact of inter-subject variability and therefore decreases the number of subjects needed to achieve statistical significance.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed.
2. 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.
3. Able to communicate well with the investigator, to understand and comply with the requirements of the study.

Exclusion Criteria:

1. 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.
2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
3. Use of topical corticosteroids or systemic immunosuppression within the last 3 weeks (for topicals) or 3 months (systemic medication)
4. 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
5. 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).
6. Significant medical problems, including but not limited to the following: uncontrolled hypertension (≥160 systolic /95 diastolic mm Hg), congestive heart failure \[New York Heart Association status of class III or IV\].
7. 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.
8. Active systemic infections during the last two weeks (exception: common cold) prior to enrollment.
9. A febrile illness within 72 hours, or major dental work within 8 days, prior to first dosing.
10. History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
11. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.
12. Inability or unwillingness to undergo repeated catheterization and / or venipuncture (e.g., because of poor tolerability or lack of access to veins). Inability or unwillingness of having a skin biopsy if consent was given.
13. Any medical or psychiatric condition or clinical laboratory abnormalities which, in the Investigator's opinion, would interfere with interpretation of study results and/or make the participant likely not to adhere to the protocol or complete the study per protocol.
14. History of venous thrombosis or known genetic predisposition to thromboembolic events
15. Subjects prone to keloid or hypertrophic scar formation or any wound healing disorder as visible by checking the vaccine insertion points on upper arm.
16. Fear of needles (belonephobia)
17. Recent (within the last three \[3\] years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc).
18. Not willing to avoid excessive sun exposure, steam baths, sauna, swimming and other strenuous activities during the study to ensure good scarring.
19. Not willing to refrain from use of skin care products applied on application sites for at least 5 days prior to start of Visit 2.

Primary outcomes:
measure: AUC
timeFrame: during 12-36h of OFM-Sampling (post-dose)
measure: CMAX
timeFrame: during 12-36h of OFM-Sampling (post-dose)
Secondary outcomes:
measure: dOFM acyclovir concentration
timeFrame: during 12-36h of OFM-Sampling (post-dose)
measure: TMAX
timeFrame: during 12-36h of OFM-Sampling (post-dose)
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University Graz
state: Styria
Study officials:
affiliation: Medical University of Graz
name: Thomas R Pieber, MD
role: PRINCIPAL_INVESTIGATOR
References: