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

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ClinicalTrials.gov Identifier: NCT01680328
Recruitment Status : Completed
First Posted : September 7, 2012
Results First Posted : June 19, 2014
Last Update Posted : March 3, 2017
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Supportive Care
Conditions Diabetes
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Delivery Systems
Interventions Other: 19 injections
Drug: sodium chloride 0.9% solution
Enrollment 82
Recruitment Details The trial was conducted at a single site in Germany at a single visit.
Pre-assignment Details  
Arm/Group Title All Participants
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 82
Subjects Missing Injections 2 [1]
Completed 80
Not Completed 2
[1]
One missed the [1600 μL, 450 μL/s; thighs]; one missed the [400 μL, 300 μL/s; abdomen]
Arm/Group Title All Participants
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 82
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 82 participants
54.3  (11.9)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 82 participants
Female
32
  39.0%
Male
50
  61.0%
1.Primary Outcome
Title Injection Pain (VAS mm)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Thighs: Injection Region-5 s.c Injections+1 Needle Insertion Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion Injection Volume 1600 μL Injection Volume 1200 μL Injection Volume 800 μL Injection Volume 400 μL Injection Speed at 450 μL/s Injection Speed at 300 μL/s Injection Speed at 150 μL/s
Hide Arm/Group Description:
Pain (VAS) was assessed in each subject for the 5 s.c injections+1 needle insertion administered in the thighs.
Pain (VAS) was assessed in each subject for the 12 s.c injections+1 needle insertion administered in the abdomen.
Pain (VAS) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s); and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Pain (VAS) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s); and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Pain (VAS) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s); and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Pain (VAS) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s); and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Pain (VAS) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s); and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Pain (VAS) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s); and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Pain (VAS) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s); and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Overall Number of Participants Analyzed 82 82 82 82 82 82 82 82 82
Mean (Standard Deviation)
Unit of Measure: mm
Needle insertion 20.0  (24.2) 12.8  (16.3) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Injection speed at 150 μL/s; Abdomen NA [1]   (NA) NA [1]   (NA) 20.9  (24.4) 15.7  (20.2) 11.6  (15.7) 14.5  (17.3) NA [1]   (NA) NA [1]   (NA) NA [2]   (NA)
Injection speed at 300 μL/s; Abdomen NA [1]   (NA) NA [1]   (NA) 17.2  (22.5) 20.1  (25.3) 13.7  (17.1) 14.8  (18.1) NA [1]   (NA) NA [2]   (NA) NA [1]   (NA)
Injection speed at 450 μL/s; Abdomen NA [1]   (NA) NA [1]   (NA) 21.1  (24.8) 14.9  (16.9) 14.8  (18.9) 12.4  (15.5) NA [2]   (NA) NA [1]   (NA) NA [1]   (NA)
Injection volume of 400 μL; Thighs NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [2]   (NA) 20.9  (24.8) NA [1]   (NA) 22.9  (25.9)
Injection volume of 800 μL; Thighs NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [2]   (NA) NA [1]   (NA) NA [1]   (NA) 23.2  (24.5) NA [1]   (NA)
Injection volume of 1600 μL; Thighs NA [1]   (NA) NA [1]   (NA) NA [2]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) 31.1  (28.5) NA [1]   (NA) 31.5  (28.0)
[1]
Not administered
[2]
No summary statistics done for this combination
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Injection Volume 800 μL, Injection Volume 400 μL
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean
Estimated Value -0.1
Confidence Interval 95%
-2.9 to 2.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Injection Volume 1200 μL, Injection Volume 400 μL
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean
Estimated Value 3.5
Confidence Interval 95%
0.4 to 6.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Injection Volume 1600 μL, Injection Volume 400 μL
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean
Estimated Value 7.2
Confidence Interval 95%
4.6 to 9.7
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Injection Volume 1200 μL, Injection Volume 800 μL
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean
Estimated Value 3.6
Confidence Interval 95%
0.4 to 6.7
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Injection Volume 1600 μL, Injection Volume 800 μL
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean
Estimated Value 7.2
Confidence Interval 95%
4.4 to 10.0
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Injection Volume 1600 μL, Injection Volume 1200 μL
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean
Estimated Value 3.7
Confidence Interval 95%
0.6 to 6.7
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Injection Speed at 300 μL/s, Injection Speed at 150 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean
Estimated Value 0.4
Confidence Interval 95%
-2.1 to 2.9
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Injection Speed at 450 μL/s, Injection Speed at 150 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean
Estimated Value -0.4
Confidence Interval 95%
-2.7 to 1.9
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Thighs: Injection Region-5 s.c Injections+1 Needle Insertion, Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean
Estimated Value 9.0
Confidence Interval 95%
6.7 to 11.3
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Acceptance of Injection Pain After Injection of Different Volumes.
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomised subjects receiving at least one injection (possibly needle insertion only) were included in the full analysis set.
Arm/Group Title Injection Volume of 1600 μL Injection Volume of 1200 μL Injection Volume of 800 μL Injection Volume of 400 μL
Hide Arm/Group Description:
Acceptance of pain was assessed in each subject for all injections.
Acceptance of pain was assessed in each subject for all injections.
Acceptance of pain was assessed in each subject for all injections.
Acceptance of pain was assessed in each subject for all injections.
Overall Number of Participants Analyzed 82 82 82 82
Measure Type: Number
Unit of Measure: scores
Yes 334 218 303 368
No 75 28 25 41
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Injection Volume of 800 μL, Injection Volume of 400 μL
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Odds ratio (OR)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.8
Confidence Interval 95%
0.5 to 1.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Injection Volume of 1200 μL, Injection Volume of 400 μL
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.1
Confidence Interval 95%
1.2 to 3.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Injection Volume of 1600 μL, Injection Volume of 400 μL
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.1
Confidence Interval 95%
1.4 to 3.0
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Injection Volume of 1200 μL, Injection Volume of 800 μL
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.6
Confidence Interval 95%
1.4 to 4.8
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Injection Volume of 1600 μL, Injection Volume of 800 μL
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.6
Confidence Interval 95%
1.4 to 4.6
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Injection Volume of 1600 μL, Injection Volume of 1200 μL
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.0
Confidence Interval 95%
0.7 to 1.5
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Acceptance of Injection Pain After Injection at Different Speeds.
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomised subjects receiving at least one injection (possibly needle insertion only) were included in the full analysis set.
Arm/Group Title Injection Speed at 450 μL/s Injection Speed at 300 μL/s Injection Speed at 150 μL/s
Hide Arm/Group Description:
Acceptance of pain was assessed in each subject for all injections.
Acceptance of pain was assessed in each subject for all injections.
Acceptance of pain was assessed in each subject for all injections.
Overall Number of Participants Analyzed 82 82 82
Measure Type: Number
Unit of Measure: scores
Yes 432 365 426
No 59 44 66
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Injection Speed at 300 μL/s, Injection Speed at 150 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.1
Confidence Interval 95%
0.7 to 1.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Injection Speed at 450 μL/s, Injection Speed at 150 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.9
Confidence Interval 95%
0.6 to 1.2
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Acceptance of Injection Pain After Injection in the Thighs Versus Abdomen.
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomised subjects receiving at least one injection (possibly needle insertion only) were included in the full analysis set.
Arm/Group Title Thighs Abdomen
Hide Arm/Group Description:
Acceptance of pain was assessed in each subject for all injections in the thighs.
Acceptance of pain was assessed in each subject for all injections in the abdomen.
Overall Number of Participants Analyzed 82 82
Measure Type: Number
Unit of Measure: scores
Yes 390 978
No 101 87
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Thighs, Abdomen
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Odds ratio (OR)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.7
Confidence Interval 95%
2.4 to 5.5
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Estimated Mean Differences in the Volume of Backflow (uL) in the Abdomen After Different Injection Volumes and Speeds as Compared to Needle Insertion
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Abdomen: Injection Region-12 s.c Injections+1 Needle Insertion Injection Volume 1600 μL Injection Volume 1200 μL Injection Volume 800 μL Injection Volume 400 μL Injection Speed at 450 μL/s Injection Speed at 300 μL/s Injection Speed at 150 μL/s
Hide Arm/Group Description:
Backflow (uL) was assessed in each subject for the 12 s.c injections+1 needle insertion administered in the abdomen.
Backflow (uL) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s), and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Backflow (uL) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s), and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Backflow (uL) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s), and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Backflow (uL) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s), and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Backflow (uL) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s), and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Backflow (uL) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s), and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Backflow (uL) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s), and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Overall Number of Participants Analyzed 82 82 82 82 82 82 82 82
Mean (Standard Deviation)
Unit of Measure: mcL
Needle insertion 0.0  (0.1) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Injection speed at 150 μL/s NA [1]   (NA) 2.3  (5.1) 0.9  (1.9) 0.5  (1.4) 0.6  (1.8) NA [1]   (NA) NA [1]   (NA) NA [2]   (NA)
Injection speed at 300 μL/s NA [1]   (NA) 1.4  (2.9) 0.8  (1.9) 0.5  (1.6) 0.4  (1.3) NA [1]   (NA) NA [2]   (NA) NA [1]   (NA)
Injection speed at 450 μL/s NA [1]   (NA) 0.6  (1.1) 1.1  (4.6) 0.5  (1.3) 0.9  (2.7) NA [2]   (NA) NA [1]   (NA) NA [1]   (NA)
[1]
Not administered
[2]
No summary statistics done for this combination
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Injection Volume 400 μL, Injection Speed at 150 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.6
Confidence Interval 95%
-0.6 to 1.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Injection Volume 400 μL, Injection Speed at 300 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.4
Confidence Interval 95%
-0.8 to 1.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Injection Volume 400 μL, Injection Speed at 450 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.9
Confidence Interval 95%
-0.4 to 2.1
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Injection Volume 800 μL, Injection Speed at 150 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.5
Confidence Interval 95%
-0.8 to 1.7
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Injection Volume 800 μL, Injection Speed at 300 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.5
Confidence Interval 95%
-0.8 to 1.7
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Injection Volume 800 μL, Injection Speed at 450 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.5
Confidence Interval 95%
-0.7 to 1.8
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Injection Volume 1200 μL, Injection Speed at 150 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.9
Confidence Interval 95%
-0.3 to 2.1
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Injection Volume 1200 μL, Injection Speed at 300 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.8
Confidence Interval 95%
-0.4 to 2.0
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Injection Volume 1200 μL, Injection Speed at 450 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 1.1
Confidence Interval 95%
-0.1 to 2.3
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Injection Volume 1600 μL, Injection Speed at 150 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 2.3
Confidence Interval 95%
1.0 to 3.5
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Injection Volume 1600 μL, Injection Speed at 300 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 1.4
Confidence Interval 95%
0.2 to 2.6
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Injection Volume 1600 μL, Injection Speed at 450 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.6
Confidence Interval 95%
-0.6 to 1.8
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Estimated Mean Differences in the Volume of Backflow (uL) in the Thighs After Different Injection Volumes and Speeds as Compared to Needle Insertion
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Thighs: Injection Region-5 s.c Injections+1 Needle Insertion Injection Volume 1600 μL Injection Volume 800 μL Injection Volume 400 μL Injection Speed at 450 μL/s Injection Speed at 300 μL/s Injection Speed at 150 μL/s
Hide Arm/Group Description:
Backflow (uL) was assessed in each subject for the 5 s.c injections+1 needle insertion administered in the thighs.
Backflow (uL) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s), and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Backflow (uL) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s), and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Backflow (uL) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s), and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Backflow (uL) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s), and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Backflow (uL) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s), and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Backflow (uL) was assessed in the abdomen following administration of 4 different injection volumes (400, 800, 1200 and 1600 µL) at 3 different injection speeds (150, 300 and 450 µL/s), and in the thighs following administration of the selected combinations of injection volume (µL) and speed (µL/s) (400/150, 400/450, 800/300, 1600/150, 1600/450).
Overall Number of Participants Analyzed 82 82 82 82 82 82 82
Mean (Standard Deviation)
Unit of Measure: mcL
Needle insertion 0.8  (5.6) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Injection speed at 150 μL/s NA [1]   (NA) 5.6  (8.6) NA [1]   (NA) 1.0  (3.1) NA [1]   (NA) NA [1]   (NA) NA [2]   (NA)
Injection speed at 300 μL/s NA [1]   (NA) NA [1]   (NA) 2.3  (7.9) NA [1]   (NA) NA [1]   (NA) NA [3]   (NA) NA [1]   (NA)
Injection speed at 450 μL/s NA [1]   (NA) 2.5  (4.6) NA [1]   (NA) 1.6  (4.9) NA [2]   (NA) NA [1]   (NA) NA [1]   (NA)
[1]
Not administered
[2]
No summary statistics done for this combination.
[3]
Summary statistics is same as presented in Injection speed at 300 μL/s x Injection Volume 800 μL.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Injection Volume 400 μL, Injection Speed at 150 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.3
Confidence Interval 95%
-0.9 to 1.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Injection Volume 400 μL, Injection Speed at 450 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.8
Confidence Interval 95%
-0.4 to 2.1
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Injection Volume 800 μL, Injection Speed at 300 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 1.6
Confidence Interval 95%
0.3 to 2.8
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Injection Volume 1600 μL, Injection Speed at 150 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 4.9
Confidence Interval 95%
3.7 to 6.1
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Injection Volume 1600 μL, Injection Speed at 450 μL/s
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 1.7
Confidence Interval 95%
0.5 to 2.9
Estimation Comments [Not Specified]
Time Frame From Day 0 when receiving 19 injections and up to 48 hours after last injection.
Adverse Event Reporting Description All randomised subjects receiving at least one injection (possibly needle insertion only) were included in the safety analysis set.
 
Arm/Group Title All Participants
Hide Arm/Group Description 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.
All-Cause Mortality
All Participants
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
All Participants
Affected / at Risk (%)
Total   0/82 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
All Participants
Affected / at Risk (%)
Total   0/82 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Novo Nordisk reserves the right to defer the release of data until specified milestones are reached, for example when the clinical trial report is available. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
Results Point of Contact
Name/Title: Public Access to Clinical Trials
Organization: Novo Nordisk A/S
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01680328     History of Changes
Other Study ID Numbers: INS-4011
U1111-1129-4191 ( Other Identifier: WHO )
First Submitted: August 31, 2012
First Posted: September 7, 2012
Results First Submitted: December 6, 2013
Results First Posted: June 19, 2014
Last Update Posted: March 3, 2017