Investigation of Pain During Subcutaneous Injections With Different Injection Speed and Volume Combinations

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of this trial is to assess and describe the pain in relation to subcutaneous (under the skin) injection of different combinations of injection speed and volume with respect to acceptance of the injection pain and backflow.

Official Title
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Investigation of Pain During Subcutaneous Injections With Different Injection Speed and Volume Combinations

Conditions
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Diabetes, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Delivery Systems

Intervention / Treatment
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* Other: 19 injections
* Drug: sodium chloride 0.9% solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activities. Type 1 or type 2 diabetes Daily injection(s) with anti-diabetic drug (insulin or Glucagon like Peptide-1 (GLP-1) analogues) via pen-injector or vial/syringe for more than 6 months Body mass index (BMI) between 18.5 and 30.0 kg/m^2 (both included) Caucasians Exclusion Criteria: Known or suspected hypersensitivity to needle, ink ball pen or other that are in contact with the injection area during the clinical visit Previous participation in this trial. Participation is defined as: screened Receipt of any investigational medicinal product that can influence pain perception within 14 days before screening Injection of more than 40 units of insulin per injection Continuous Subcutaneous Insulin Infusion use within the last 6 months Continuous Glucose Monitoring use within the last 6 months Intake of any pain-relieving or analgesic within the last week (excluding low dose aspirin in cardio vascular prophylactic doses) Known active or in-active skin disease in the injection area or that may affect pain perception Anti-coagulant treatment within the last month (low dose of aspirin in cardiovascular prophylactic doses is allowed. However, not on the day of the injections)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Different injection speed and volume combinations<br>The study consists of 80 treatment arms in a cross-over design with 19 treatments and 19 periods. The 80 treatment arms will represent different orders of the 19 treatments and each treatment arm will be used for one subject. A subject not completing all treatments will be replaced by another subject using the same treatment arm. | Other: 19 injections<br>* Subjects will receive 19 injections in randomised order of which 13 will be in the abdomen and 6 in the thighs. Out of the 19 injections, 2 are needle insertions only. The remaining 17 injections represent different combinations of injection speed and volume of sodium chloride 0.9% solution for injection. The order of the injection speed and volume combinations will be blinded for the subject and the pain will be evaluated by the subject on a VAS (Visual Analogue Scale).<br>Drug: sodium chloride 0.9% solution<br>* Solution for injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Injection Pain (VAS mm) | Calculated as the least square mean estimate of the difference in injection pain on a VAS (mm) between different factor levels corresponding to injection region, injection volume and injection speed (pain was assessed using an electronic VAS consisting of a 100 mm line where 0 mm corresponded to no pain and 100 mm corresponded to worst pain. After each injection, the subjects rated their pain perception at the electronic VAS by marking the 100 mm line). | 1 minute (±30 sec) after each injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptance of Injection Pain After Injection of Different Volumes. | Acceptance of pain was rated subjectively as yes or no by the subject after each injection. | 1 minute (±30 seconds) after each injection | 
| Acceptance of Injection Pain After Injection at Different Speeds. | Acceptance of pain was rated subjectively as yes or no by the subject after each injection. | 1 minute (±30 sec) after each injection | 
| Acceptance of Injection Pain After Injection in the Thighs Versus Abdomen. | Acceptance of pain was rated subjectively as yes or no by the subject after each injection. | 1 minute (±30 seconds) after each injection | 
| Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Backflow was measured after each injection by placing a filter paper over the injection site after the injection was given and until the liquid was absorbed. The size of the wet spot on the filter paper served as a measure of the backflow. The treatment effect on backflow was calculated as the least square mean estimate of the difference in backflow after injection in the abdomen at different volume and speed combinations. | 2 minutes (±30sec) after each injection | 
| Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Backflow was measured after each injection by placing a filter paper over the injection site after the injection was given and until the liquid was absorbed. The size of the wet spot on the filter paper served as a measure of the backflow. The treatment effect on backflow was calculated as the least square mean estimate of the difference in backflow after injection in the abdomen at different volume and speed combinations. | 2 minutes (±30sec) after each injection |