Transdermal Insulin Response In Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
Bio-fermentation produced Human insulin is available without prescription in the U.S. This study is a physician-initiated trial of a formula enabling transdermal delivery of human insulin.

Detailed Description
-----------------
The primary objective of the study is to determine the amount of lowering serum glucose as a function of dose of a topically applied formulation of Human Insulin administered by syringe measurement to adult Healthy Volunteer subjects as compared to no treatment. A 5-day period of daily blood sugar monitoring by means of wearable Continuous Glucose Monitor and insulin dosing for 3 days then monitoring for at least 3 days following will form the baseline and experimental data for each subject. The secondary objective is to evaluate the tolerability and local and systemic effects of transdermal Human Insulin if any.

Official Title
-----------------
A Physician-Initiated Randomised, Multiple-Dose, Single Period, Phase II Dose Ranging Study to Examine Transdermal Human Insulin In Adult Healthy Volunteer Patients

Conditions
-----------------
Pharmacodynamic Response to Small Doses of Insulin

Intervention / Treatment
-----------------
* Combination Product: Human insulin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subject has a serum protein HbA1c of less than 6. The subject is willing and able to read, understand the Subject Information Sheet and provide written informed consent. The subject has a body mass index (BMI) within 18-50 kg/m2. The subject is in otherwise good health as determined by medical history and physical examination. The subject is a non-smoker. The subject must agree to continue with daily serum glucose testing by means of a wearable blood glucose for the pharmacokinetic assessments. The subject is willing and able to comply with all testing and requirements defined in the protocol. The subject is willing and able to return to the study site for all visits. Exclusion Criteria: The subject has any relevant deviations from normal other than blood glucose in physical examination, electrocardiogram (ECG), or clinical laboratory tests, as evaluated by the investigator. The subject has had a clinically significant illness within 30 days preceding entry into this study. The subject has a history of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease. The subject has a known allergy or history of hypersensitivity to Human Insulin or similar modified Insulin compounds. The subject has used any prescription medication that may interfere with the evaluation of study medication. The subject has donated or lost a significant volume of blood (>450 mL) within four (4) weeks of the study, and their Haemoglobin concentration and haematocrit have not returned to within 5% of normal. The subject has a history of substance abuse or a current positive urine drug screen or urine alcohol test. Alcohol consumption greater than community norms (i.e. more than 21 standard drinks per week for males). Subjects who have received an investigational drug or have used an investigational device in the 30 days prior to study entry

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Interventional Model Description: Healthy Males, aged 20 to 60, Non-diabetic and Hemoglobin A1c test results of less than 6.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Main Experimental<br>Each subject will receive doses applied to the skin of 0.075 IUs / Kilogram Body Weight, 0.1 IUs/Kilogram Body Weight and 0.15 IUs /Kilogram Body Weight | Combination Product: Human insulin<br>* Human Insulin from recombinant source delivered in a solution capable of enabling transdermal delivery formulated at 100 IU/mL of delivery vehicle.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial Serum Glucose in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin Averaged Per Subject | An Average Postprandial serum glucose measured by the Continuous Glucose Monitor as a response to a single dose of Human Insulin averaged (Mean) for each Subject. Data is reported in mg/dL. The Average reported was a comparison from Baseline (Day 1) and up to 3.5 hours following each dose (assessed at Day 1 - Baseline, Day 2 - Dose 1, Day 3 - Dose 2, and Day 4 - Dose 3) | Pre-dose Baseline & a Mean of readings over 3.5 hours | 
| Daily Average Serum Glucose Measured in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin | Daily average serum glucose measured by the Continuous Glucose Monitor in measured in mg/dL as a response to a single dose of Human Insulin and reported by the Freestyle 14-day software. Data was collected 4 times an hour throughout the test period and across doses. The prandial segments were included in this average. Data is reported in mg/dL by subject. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OECD Acute Dermal Irritation/Corrosion Score According to to the Organisation for Economic Co-operation and Development (OECD) Guideline for Testing of Chemicals No. 404 | The skin at the application site will be assessed at each Clinic Visit by the investigator and/or Study Nurse. Any dermal irritation will be scored according to to the Organisation for Economic Co-operation and Development (OECD) Guideline for Testing of Chemicals No. 404, adopted 17th July, 1992: Acute Dermal Irritation/Corrosion and any score of 0 or greater will be reported. The Guideline is a scale of from Zero (No erythema or edema), 1: Very slight, 2: Well-defined erythema/Slight edema (edges of area well-defined by definite raising), 3: Moderate to severe erythema/Moderate edema (raised approximately 1 mm) to 4: Severe erythema (beet redness) to eschar formation preventing grading / Severe edema (raised more than 1 mm, extending beyond area of exposure). The higher the score the worse the erythema or edema, so a score of 0 is very good and a score of 4 is very bad. | 20 Days |