Pharmacodynamic Response to Small Doses of Insulin
Conditions
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.
Interventions
COMBINATION_PRODUCTHuman insulin
Human Insulin from recombinant source delivered in a solution capable of enabling transdermal delivery formulated at 100 IU/mL of delivery vehicle.
Sponsors
Langford Research Institute, Inc.
Transdermal Delivery Solutions Corp
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DEVICE_FEASIBILITY
Masking
NONE
Intervention model description
Healthy Males, aged 20 to 60, Non-diabetic and Hemoglobin A1c test results of less than 6.
Eligibility
Sex/Gender
MALE
Age
20 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. The subject has a serum protein HbA1c of less than 6. 2. The subject is willing and able to read, understand the Subject Information Sheet and provide written informed consent. 3. The subject has a body mass index (BMI) within 18-50 kg/m2. 4. The subject is in otherwise good health as determined by medical history and physical examination. 5. The subject is a non-smoker. 6. The subject must agree to continue with daily serum glucose testing by means of a wearable blood glucose for the pharmacokinetic assessments. 7. The subject is willing and able to comply with all testing and requirements defined in the protocol. 8. The subject is willing and able to return to the study site for all visits.
Exclusion criteria
1. 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. 2. The subject has had a clinically significant illness within 30 days preceding entry into this study. 3. The subject has a history of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease. 4. The subject has a known allergy or history of hypersensitivity to Human Insulin or similar modified Insulin compounds. 5. The subject has used any prescription medication that may interfere with the evaluation of study medication. 6. 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. 7. The subject has a history of substance abuse or a current positive urine drug screen or urine alcohol test. 8. Alcohol consumption greater than community norms (i.e. more than 21 standard drinks per week for males). 9. Subjects who have received an investigational drug or have used an investigational device in the 30 days prior to study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postprandial Serum Glucose in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin Averaged Per Subject | Pre-dose Baseline & a Mean of readings over 3.5 hours | 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) |
| Daily Average Serum Glucose Measured in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin | 72 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 20 Days | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects (Ss) were recruited by word-of-mouth and attended a study orientation where the study participation expectations were discussed and the informed consent forms provided. Ss underwent a health screening to ascertain healthy, non diabetic status.
Pre-assignment details
7 Volunteers were asked to undergo a physical exam including a complete metabolic panel via blood sample.
Participants by arm
| Arm | Count |
|---|---|
| Main Experimental 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
Human insulin: Human Insulin from recombinant source delivered in a solution capable of enabling transdermal delivery formulated at 100 IU/mL of delivery vehicle. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Main Experimental |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Average Untreated Serum Glucose | 96.4 mg/dL |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
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.
Time frame: 72 hours
Population: 7 healthy volunteers were recruited. Data from 2 of the subjects was not included, in both cases because of lack of compliance with device polling instructions. Subjects were directed to poll the sensor at least every 8 hours and follow a typical 3 meal schedule and these 2 subjects were unable to comply and or had device issues.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dose 1 | Daily Average Serum Glucose Measured in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin | 95 mg/dL Serum Glucose |
| Dose 2 | Daily Average Serum Glucose Measured in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin | 99 mg/dL Serum Glucose |
| Dose 3 | Daily Average Serum Glucose Measured in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin | 85 mg/dL Serum Glucose |
| Subject 5 | Daily Average Serum Glucose Measured in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin | 89 mg/dL Serum Glucose |
| Subject 6 | Daily Average Serum Glucose Measured in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin | 103 mg/dL Serum Glucose |
Comparison: Subject received doses applied to the skin of 0.075, 0.10 and 0.15 IUs / Kilogram on successive days. The Subject's average Serum Glucose for these 3 days were compared against the Subject's baseline unmedicated Serum Glucose on non-dosed days.p-value: 0t-test, 1 sided
Comparison: Subject received doses applied to the skin of 0.075, 0.10 and 0.15 IUs / Kilogram on successive days. The Subject's average Serum Glucose for these 3 days were compared against the Subject's baseline unmedicated Serum Glucose on non-dosed days.p-value: 0.000003t-test, 1 sided
p-value: 0.000002t-test, 1 sided
p-value: 0.000035t-test, 1 sided
p-value: 0.000004t-test, 1 sided
Primary
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)
Time frame: Pre-dose Baseline & a Mean of readings over 3.5 hours
Population: We recruited and entered 7 healthy individuals into the study. We did not include data from 2 Subjects due to non-compliance with the protocol.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dose 1 | Postprandial Serum Glucose in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin Averaged Per Subject | 3.8 mg/dL |
| Dose 2 | Postprandial Serum Glucose in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin Averaged Per Subject | -1.8 mg/dL |
| Dose 3 | Postprandial Serum Glucose in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin Averaged Per Subject | 7 mg/dL |
Comparison: Glucose was monitored by means of a wearable Continuous Glucose Monitor for several days prior to, during and post dosing. Measurements were gathered for each subject and averaged within-subject data. Our null hypothesis was that post prandial serum glucose would not vary significantly from their baseline values.p-value: 0.000016ANOVA
Secondary
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.
Time frame: 20 Days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose 1 | 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 | 0 units on a scale |
p-value: 0ANOVA