Delivery Systems, Diabetes, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
Conditions
Brief summary
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.
Interventions
OTHER19 injections
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).
Solution for injection.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Injection Pain (VAS mm) | 1 minute (±30 sec) after each injection | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acceptance of Injection Pain After Injection of Different Volumes. | 1 minute (±30 seconds) after each injection | Acceptance of pain was rated subjectively as yes or no by the subject after each injection. |
| Acceptance of Injection Pain After Injection at Different Speeds. | 1 minute (±30 sec) after each injection | Acceptance of pain was rated subjectively as yes or no by the subject after each injection. |
| Acceptance of Injection Pain After Injection in the Thighs Versus Abdomen. | 1 minute (±30 seconds) after each injection | Acceptance of pain was rated subjectively as yes or no by the subject 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 | 2 minutes (±30sec) after each injection | 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. |
| Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | 2 minutes (±30sec) after each injection | 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. |
Countries
Germany
Participant flow
Recruitment details
The trial was conducted at a single site in Germany at a single visit.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Subjects received 19 subcutaneous (s.c) injections. Of the 19 injections, 13 were in the abdomen and 6 in the thighs. Of the 13 injections in the abdomen, 1 was a needle insertion and 12 were combinations of the 4 different injection volumes (400, 800, 1200 and 1600 µL) and 3 injection speeds (150, 300 and 450 µL/s). Of the 6 injections in the thigh, 1 was a needle insertion and 5 were selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450). Except for the 2 needle insertions, sodium chloride 0.9% solution was injected. | 82 |
| Total | 82 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 11.9 |
| Gender Female | 32 Participants |
| Gender Male | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 82 |
| serious Total, serious adverse events | 0 / 82 |
Outcome results
Primary
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).
Time frame: 1 minute (±30 sec) after each injection
Population: All randomised subjects receiving at least one injection (possibly needle insertion only) were included in the full analysis set. A total of 4 subjects did not contribute to the analysis due to missing injections (2) and missing VAS evaluation (2).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Injection speed at 300 μL/s; Abdomen | NA mm | — |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Injection speed at 450 μL/s; Abdomen | NA mm | — |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Needle insertion | 20.0 mm | Standard Deviation 24.2 |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Injection volume of 1600 μL; Thighs | NA mm | — |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Injection volume of 800 μL; Thighs | NA mm | — |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Injection speed at 150 μL/s; Abdomen | NA mm | — |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Injection volume of 400 μL; Thighs | NA mm | — |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Injection volume of 1600 μL; Thighs | NA mm | — |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Injection volume of 800 μL; Thighs | NA mm | — |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Injection speed at 450 μL/s; Abdomen | NA mm | — |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Injection speed at 150 μL/s; Abdomen | NA mm | — |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Needle insertion | 12.8 mm | Standard Deviation 16.3 |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Injection volume of 400 μL; Thighs | NA mm | — |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Injection Pain (VAS mm) | Injection speed at 300 μL/s; Abdomen | NA mm | — |
| Injection Volume 1600 μL | Injection Pain (VAS mm) | Injection volume of 1600 μL; Thighs | NA mm | — |
| Injection Volume 1600 μL | Injection Pain (VAS mm) | Injection volume of 800 μL; Thighs | NA mm | — |
| Injection Volume 1600 μL | Injection Pain (VAS mm) | Injection speed at 300 μL/s; Abdomen | 17.2 mm | Standard Deviation 22.5 |
| Injection Volume 1600 μL | Injection Pain (VAS mm) | Injection speed at 450 μL/s; Abdomen | 21.1 mm | Standard Deviation 24.8 |
| Injection Volume 1600 μL | Injection Pain (VAS mm) | Needle insertion | NA mm | — |
| Injection Volume 1600 μL | Injection Pain (VAS mm) | Injection volume of 400 μL; Thighs | NA mm | — |
| Injection Volume 1600 μL | Injection Pain (VAS mm) | Injection speed at 150 μL/s; Abdomen | 20.9 mm | Standard Deviation 24.4 |
| Injection Volume 1200 μL | Injection Pain (VAS mm) | Injection volume of 800 μL; Thighs | NA mm | — |
| Injection Volume 1200 μL | Injection Pain (VAS mm) | Needle insertion | NA mm | — |
| Injection Volume 1200 μL | Injection Pain (VAS mm) | Injection speed at 150 μL/s; Abdomen | 15.7 mm | Standard Deviation 20.2 |
| Injection Volume 1200 μL | Injection Pain (VAS mm) | Injection speed at 300 μL/s; Abdomen | 20.1 mm | Standard Deviation 25.3 |
| Injection Volume 1200 μL | Injection Pain (VAS mm) | Injection speed at 450 μL/s; Abdomen | 14.9 mm | Standard Deviation 16.9 |
| Injection Volume 1200 μL | Injection Pain (VAS mm) | Injection volume of 400 μL; Thighs | NA mm | — |
| Injection Volume 1200 μL | Injection Pain (VAS mm) | Injection volume of 1600 μL; Thighs | NA mm | — |
| Injection Volume 800 μL | Injection Pain (VAS mm) | Injection volume of 800 μL; Thighs | NA mm | — |
| Injection Volume 800 μL | Injection Pain (VAS mm) | Needle insertion | NA mm | — |
| Injection Volume 800 μL | Injection Pain (VAS mm) | Injection speed at 150 μL/s; Abdomen | 11.6 mm | Standard Deviation 15.7 |
| Injection Volume 800 μL | Injection Pain (VAS mm) | Injection speed at 300 μL/s; Abdomen | 13.7 mm | Standard Deviation 17.1 |
| Injection Volume 800 μL | Injection Pain (VAS mm) | Injection volume of 400 μL; Thighs | NA mm | — |
| Injection Volume 800 μL | Injection Pain (VAS mm) | Injection volume of 1600 μL; Thighs | NA mm | — |
| Injection Volume 800 μL | Injection Pain (VAS mm) | Injection speed at 450 μL/s; Abdomen | 14.8 mm | Standard Deviation 18.9 |
| Injection Volume 400 μL | Injection Pain (VAS mm) | Injection speed at 300 μL/s; Abdomen | 14.8 mm | Standard Deviation 18.1 |
| Injection Volume 400 μL | Injection Pain (VAS mm) | Injection speed at 150 μL/s; Abdomen | 14.5 mm | Standard Deviation 17.3 |
| Injection Volume 400 μL | Injection Pain (VAS mm) | Injection volume of 1600 μL; Thighs | NA mm | — |
| Injection Volume 400 μL | Injection Pain (VAS mm) | Injection speed at 450 μL/s; Abdomen | 12.4 mm | Standard Deviation 15.5 |
| Injection Volume 400 μL | Injection Pain (VAS mm) | Injection volume of 400 μL; Thighs | NA mm | — |
| Injection Volume 400 μL | Injection Pain (VAS mm) | Injection volume of 800 μL; Thighs | NA mm | — |
| Injection Volume 400 μL | Injection Pain (VAS mm) | Needle insertion | NA mm | — |
| Injection Speed at 450 μL/s | Injection Pain (VAS mm) | Injection volume of 400 μL; Thighs | 20.9 mm | Standard Deviation 24.8 |
| Injection Speed at 450 μL/s | Injection Pain (VAS mm) | Injection speed at 150 μL/s; Abdomen | NA mm | — |
| Injection Speed at 450 μL/s | Injection Pain (VAS mm) | Needle insertion | NA mm | — |
| Injection Speed at 450 μL/s | Injection Pain (VAS mm) | Injection volume of 800 μL; Thighs | NA mm | — |
| Injection Speed at 450 μL/s | Injection Pain (VAS mm) | Injection speed at 450 μL/s; Abdomen | NA mm | — |
| Injection Speed at 450 μL/s | Injection Pain (VAS mm) | Injection speed at 300 μL/s; Abdomen | NA mm | — |
| Injection Speed at 450 μL/s | Injection Pain (VAS mm) | Injection volume of 1600 μL; Thighs | 31.1 mm | Standard Deviation 28.5 |
| Injection Speed at 300 μL/s | Injection Pain (VAS mm) | Injection speed at 300 μL/s; Abdomen | NA mm | — |
| Injection Speed at 300 μL/s | Injection Pain (VAS mm) | Injection speed at 150 μL/s; Abdomen | NA mm | — |
| Injection Speed at 300 μL/s | Injection Pain (VAS mm) | Injection speed at 450 μL/s; Abdomen | NA mm | — |
| Injection Speed at 300 μL/s | Injection Pain (VAS mm) | Injection volume of 1600 μL; Thighs | NA mm | — |
| Injection Speed at 300 μL/s | Injection Pain (VAS mm) | Injection volume of 400 μL; Thighs | NA mm | — |
| Injection Speed at 300 μL/s | Injection Pain (VAS mm) | Needle insertion | NA mm | — |
| Injection Speed at 300 μL/s | Injection Pain (VAS mm) | Injection volume of 800 μL; Thighs | 23.2 mm | Standard Deviation 24.5 |
| Injection Speed at 150 μL/s | Injection Pain (VAS mm) | Injection volume of 800 μL; Thighs | NA mm | — |
| Injection Speed at 150 μL/s | Injection Pain (VAS mm) | Injection volume of 1600 μL; Thighs | 31.5 mm | Standard Deviation 28 |
| Injection Speed at 150 μL/s | Injection Pain (VAS mm) | Needle insertion | NA mm | — |
| Injection Speed at 150 μL/s | Injection Pain (VAS mm) | Injection volume of 400 μL; Thighs | 22.9 mm | Standard Deviation 25.9 |
| Injection Speed at 150 μL/s | Injection Pain (VAS mm) | Injection speed at 450 μL/s; Abdomen | NA mm | — |
| Injection Speed at 150 μL/s | Injection Pain (VAS mm) | Injection speed at 150 μL/s; Abdomen | NA mm | — |
| Injection Speed at 150 μL/s | Injection Pain (VAS mm) | Injection speed at 300 μL/s; Abdomen | NA mm | — |
Comparison: Though the sample size was not based on any formal sample size or power calculations as no statistical tests were pre-specified to address the endpoints, a sample size of 80 completers was derived from a simulation study. Mean Difference in injection pain on VAS after injection of different volumes was calculated as least square mean estimate of the mean difference in injection pain.95% CI: [-2.9, 2.8]
Comparison: Though the sample size was not based on any formal sample size or power calculations as no statistical tests were pre-specified to address the endpoints, a sample size of 80 completers was derived from a simulation study. Mean Difference in injection pain on VAS after injection of different volumes was calculated as least square mean estimate of the mean difference in injection pain.95% CI: [0.4, 6.6]
Comparison: Though the sample size was not based on any formal sample size or power calculations as no statistical tests were pre-specified to address the endpoints, a sample size of 80 completers was derived from a simulation study. Mean Difference in injection pain on VAS after injection of different volumes was calculated as least square mean estimate of the mean difference in injection pain.95% CI: [4.6, 9.7]
Comparison: Though the sample size was not based on any formal sample size or power calculations as no statistical tests were pre-specified to address the endpoints, a sample size of 80 completers was derived from a simulation study. Mean Difference in injection pain on VAS after injection of different volumes was calculated as least square mean estimate of the mean difference in injection pain.95% CI: [0.4, 6.7]
Comparison: Though the sample size was not based on any formal sample size or power calculations as no statistical tests were pre-specified to address the endpoints, a sample size of 80 completers was derived from a simulation study. Mean Difference in injection pain on VAS after injection of different volumes was calculated as least square mean estimate of the mean difference in injection pain.95% CI: [4.4, 10]
Comparison: Though the sample size was not based on any formal sample size or power calculations as no statistical tests were pre-specified to address the endpoints, a sample size of 80 completers was derived from a simulation study. Mean Difference in injection pain on VAS after injection of different volumes was calculated as least square mean estimate of the mean difference in injection pain.95% CI: [0.6, 6.7]
Comparison: Though the sample size was not based on any formal sample size or power calculations as no statistical tests were pre-specified to address the endpoints, a sample size of 80 completers was derived from a simulation study. Mean difference in injection pain on VAS after injection at different speeds was calculated as least square mean estimate of the mean difference in injection pain on a VAS after injection at different speeds.95% CI: [-2.1, 2.9]
Comparison: Though the sample size was not based on any formal sample size or power calculations as no statistical tests were pre-specified to address the endpoints, a sample size of 80 completers was derived from a simulation study. Mean difference in injection pain on VAS after injection at different speeds was calculated as least square mean estimate of the mean difference in injection pain on a VAS after injection at different speeds.95% CI: [-2.7, 1.9]
Comparison: Though the sample size was not based on any formal sample size or power calculations as no statistical tests were pre-specified to address the endpoints, a sample size of 80 completers was derived from a simulation study. The mean difference in injection pain on a VAS (mm) between the thighs and abdomen was calculated as the least square mean estimate of the mean difference in injection pain on a VAS (mm) between the thighs and abdomen.95% CI: [6.7, 11.3]
Secondary
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.
Time frame: 1 minute (±30 sec) after each injection
Population: All randomised subjects receiving at least one injection (possibly needle insertion only) were included in the full analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Acceptance of Injection Pain After Injection at Different Speeds. | Yes | 432 scores |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Acceptance of Injection Pain After Injection at Different Speeds. | No | 59 scores |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Acceptance of Injection Pain After Injection at Different Speeds. | Yes | 365 scores |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Acceptance of Injection Pain After Injection at Different Speeds. | No | 44 scores |
| Injection Volume 1600 μL | Acceptance of Injection Pain After Injection at Different Speeds. | No | 66 scores |
| Injection Volume 1600 μL | Acceptance of Injection Pain After Injection at Different Speeds. | Yes | 426 scores |
Comparison: Acceptance of pain was rated subjectively as yes or no by the subject after each injection. The odds are calculated as 'no versus yes', and 'higher speed versus lower', so that an odds ratio above 1 corresponds to a higher frequency of unacceptable pain for the higher speed - i.e. a worse condition. The odd ratios for unacceptable injection pain are based on a statistical model for all acceptance pain data.95% CI: [0.7, 1.8]
Comparison: Acceptance of pain was rated subjectively as yes or no by the subject after each injection. The odds are calculated as 'no versus yes', and 'higher speed versus lower', so that an odds ratio above 1 corresponds to a higher frequency of unacceptable pain for the higher speed - i.e. a worse condition. The odd ratios for unacceptable injection pain are based on a statistical model for all acceptance pain data.95% CI: [0.6, 1.2]
Secondary
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.
Time frame: 1 minute (±30 seconds) after each injection
Population: All randomised subjects receiving at least one injection (possibly needle insertion only) were included in the full analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Acceptance of Injection Pain After Injection in the Thighs Versus Abdomen. | Yes | 390 scores |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Acceptance of Injection Pain After Injection in the Thighs Versus Abdomen. | No | 101 scores |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Acceptance of Injection Pain After Injection in the Thighs Versus Abdomen. | Yes | 978 scores |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Acceptance of Injection Pain After Injection in the Thighs Versus Abdomen. | No | 87 scores |
Comparison: Acceptance of pain was rated subjectively as yes or no by the subject after each injection. The odds are calculated as 'no versus yes', so that an odds ratio above 1 corresponds to a higher frequency of unacceptable pain in the thighs - i.e. a worse condition.95% CI: [2.4, 5.5]Odds ratio (OR)
Secondary
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.
Time frame: 1 minute (±30 seconds) after each injection
Population: All randomised subjects receiving at least one injection (possibly needle insertion only) were included in the full analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Acceptance of Injection Pain After Injection of Different Volumes. | Yes | 334 scores |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Acceptance of Injection Pain After Injection of Different Volumes. | No | 75 scores |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Acceptance of Injection Pain After Injection of Different Volumes. | No | 28 scores |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Acceptance of Injection Pain After Injection of Different Volumes. | Yes | 218 scores |
| Injection Volume 1600 μL | Acceptance of Injection Pain After Injection of Different Volumes. | Yes | 303 scores |
| Injection Volume 1600 μL | Acceptance of Injection Pain After Injection of Different Volumes. | No | 25 scores |
| Injection Volume 1200 μL | Acceptance of Injection Pain After Injection of Different Volumes. | Yes | 368 scores |
| Injection Volume 1200 μL | Acceptance of Injection Pain After Injection of Different Volumes. | No | 41 scores |
Comparison: Acceptance of pain was rated subjectively as yes or no by the subject after each injection. The odds are calculated as 'no versus yes', and 'larger volume versus smaller', so that an odds ratio above 1 corresponds to a higher frequency of unacceptable pain for the larger volume - i.e. a worse condition. The odd ratios for unacceptable injection pain are based on a statistical model for all acceptance pain data.95% CI: [0.5, 1.4]Odds ratio (OR)
Comparison: Acceptance of pain was rated subjectively as yes or no by the subject after each injection. The odds are calculated as 'no versus yes', and 'larger volume versus smaller', so that an odds ratio above 1 corresponds to a higher frequency of unacceptable pain for the larger volume - i.e. a worse condition. The odd ratios for unacceptable injection pain are based on a statistical model for all acceptance pain data.95% CI: [1.2, 3.5]
Comparison: Acceptance of pain was rated subjectively as yes or no by the subject after each injection. The odds are calculated as 'no versus yes', and 'larger volume versus smaller', so that an odds ratio above 1 corresponds to a higher frequency of unacceptable pain for the larger volume - i.e. a worse condition. The odd ratios for unacceptable injection pain are based on a statistical model for all acceptance pain data.95% CI: [1.4, 3]
Comparison: Acceptance of pain was rated subjectively as yes or no by the subject after each injection. The odds are calculated as 'no versus yes', and 'larger volume versus smaller', so that an odds ratio above 1 corresponds to a higher frequency of unacceptable pain for the larger volume - i.e. a worse condition. The odd ratios for unacceptable injection pain are based on a statistical model for all acceptance pain data.95% CI: [1.4, 4.8]
Comparison: Acceptance of pain was rated subjectively as yes or no by the subject after each injection. The odds are calculated as 'no versus yes', and 'larger volume versus smaller', so that an odds ratio above 1 corresponds to a higher frequency of unacceptable pain for the larger volume - i.e. a worse condition. The odd ratios for unacceptable injection pain are based on a statistical model for all acceptance pain data.95% CI: [1.4, 4.6]
Comparison: Acceptance of pain was rated subjectively as yes or no by the subject after each injection. The odds are calculated as 'no versus yes', and 'larger volume versus smaller', so that an odds ratio above 1 corresponds to a higher frequency of unacceptable pain for the larger volume - i.e. a worse condition. The odd ratios for unacceptable injection pain are based on a statistical model for all acceptance pain data.95% CI: [0.7, 1.5]
Secondary
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.
Time frame: 2 minutes (±30sec) after each injection
Population: All randomised subjects receiving at least one injection (possibly needle insertion only) were included in the full analysis set. One subject did not contribute to the analysis due to missing injection.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | 0.0 mcL | Standard Deviation 0.1 |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | NA mcL | — |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | NA mcL | — |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | NA mcL | — |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | 0.6 mcL | Standard Deviation 1.1 |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | 2.3 mcL | Standard Deviation 5.1 |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | NA mcL | — |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | 1.4 mcL | Standard Deviation 2.9 |
| Injection Volume 1600 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | NA mcL | — |
| Injection Volume 1600 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | 1.1 mcL | Standard Deviation 4.6 |
| Injection Volume 1600 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | 0.9 mcL | Standard Deviation 1.9 |
| Injection Volume 1600 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | 0.8 mcL | Standard Deviation 1.9 |
| Injection Volume 1200 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | NA mcL | — |
| Injection Volume 1200 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | 0.5 mcL | Standard Deviation 1.4 |
| Injection Volume 1200 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | 0.5 mcL | Standard Deviation 1.6 |
| Injection Volume 1200 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | 0.5 mcL | Standard Deviation 1.3 |
| Injection Volume 800 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | 0.9 mcL | Standard Deviation 2.7 |
| Injection Volume 800 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | 0.4 mcL | Standard Deviation 1.3 |
| Injection Volume 800 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | 0.6 mcL | Standard Deviation 1.8 |
| Injection Volume 800 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | NA mcL | — |
| Injection Volume 400 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | NA mcL | — |
| Injection Volume 400 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | NA mcL | — |
| Injection Volume 400 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | NA mcL | — |
| Injection Volume 400 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | NA mcL | — |
| Injection Speed at 450 μL/s | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | NA mcL | — |
| Injection Speed at 450 μL/s | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | NA mcL | — |
| Injection Speed at 450 μL/s | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | NA mcL | — |
| Injection Speed at 450 μL/s | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | NA mcL | — |
| Injection Speed at 300 μL/s | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | NA mcL | — |
| Injection Speed at 300 μL/s | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | NA mcL | — |
| Injection Speed at 300 μL/s | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | NA mcL | — |
| Injection Speed at 300 μL/s | Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | NA mcL | — |
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the abdomen at different volume and speed combinations.95% CI: [-0.6, 1.8]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the abdomen at different volume and speed combinations.95% CI: [-0.8, 1.6]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the abdomen at different volume and speed combinations.95% CI: [-0.4, 2.1]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the abdomen at different volume and speed combinations.95% CI: [-0.8, 1.7]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the abdomen at different volume and speed combinations.95% CI: [-0.8, 1.7]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the abdomen at different volume and speed combinations.95% CI: [-0.7, 1.8]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the abdomen at different volume and speed combinations.95% CI: [-0.3, 2.1]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the abdomen at different volume and speed combinations.95% CI: [-0.4, 2]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the abdomen at different volume and speed combinations.95% CI: [-0.1, 2.3]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the abdomen at different volume and speed combinations.95% CI: [1, 3.5]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the abdomen at different volume and speed combinations.95% CI: [0.2, 2.6]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the abdomen at different volume and speed combinations.95% CI: [-0.6, 1.8]
Secondary
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.
Time frame: 2 minutes (±30sec) after each injection
Population: All randomised subjects receiving at least one injection (possibly needle insertion only) were included in the full analysis set. One subject did not contribute to the analysis due to missing injection.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | 0.8 mcL | Standard Deviation 5.6 |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | NA mcL | — |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | NA mcL | — |
| Thighs: Injection Region-5 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | NA mcL | — |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | 2.5 mcL | Standard Deviation 4.6 |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | NA mcL | — |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | NA mcL | — |
| Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | 5.6 mcL | Standard Deviation 8.6 |
| Injection Volume 1600 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | 2.3 mcL | Standard Deviation 7.9 |
| Injection Volume 1600 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | NA mcL | — |
| Injection Volume 1600 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | NA mcL | — |
| Injection Volume 1600 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | NA mcL | — |
| Injection Volume 1200 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | NA mcL | — |
| Injection Volume 1200 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | 1.0 mcL | Standard Deviation 3.1 |
| Injection Volume 1200 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | NA mcL | — |
| Injection Volume 1200 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | 1.6 mcL | Standard Deviation 4.9 |
| Injection Volume 800 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | NA mcL | — |
| Injection Volume 800 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | NA mcL | — |
| Injection Volume 800 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | NA mcL | — |
| Injection Volume 800 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | NA mcL | — |
| Injection Volume 400 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | NA mcL | — |
| Injection Volume 400 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | NA mcL | — |
| Injection Volume 400 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | NA mcL | — |
| Injection Volume 400 μL | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | NA mcL | — |
| Injection Speed at 450 μL/s | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 300 μL/s | NA mcL | — |
| Injection Speed at 450 μL/s | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Needle insertion | NA mcL | — |
| Injection Speed at 450 μL/s | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 150 μL/s | NA mcL | — |
| Injection Speed at 450 μL/s | Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion | Injection speed at 450 μL/s | NA mcL | — |
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the thigh at different volume and speed combinations.95% CI: [-0.9, 1.5]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the thigh at different volume and speed combinations.95% CI: [-0.4, 2.1]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the thigh at different volume and speed combinations.95% CI: [0.3, 2.8]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the thigh at different volume and speed combinations.95% CI: [3.7, 6.1]
Comparison: Backflow (absorbed amount of liquid 2 minutes (±30 sec) after the injection with filter-paper rated according to the liquid scale) was analysed using a mixed ANOVA approach and calculated as the mean differences in backflow in the thigh at different volume and speed combinations.95% CI: [0.5, 2.9]