Comparison of Glycemic Control in Obese Diabetics Using Three Different Pen Needles

• Sponsor: Becton, Dickinson and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01231984
• Collaborator: (none)
• Enrollment: 293
• Locations: 10
• Arms: 2
• Duration (Months): 19
• Patients Per Site: 29.3
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

Anxiety about needles is a concern commonly expressed by diabetics when beginning insulin therapy. A shorter, thinner pen needle that delivers insulin with the safety and efficacy profile of longer pen needles may appeal to many diabetic patients as the shorter needle may be perceived as less intimidating and more comfortable. While pen needles of 4 to 8 mm in length are generally used for insulin injection in patients considered thin or normal weight, longer (12.7 mm) needles are still often prescribed for overweight or obese patients with diabetes. Since skin thickness is nearly constant across a range of body mass index (BMI), a clear rationale exists for the use of shorter needles in obese patients. (Gibney et al., CMRO 2010)

The primary purpose of this study is to evaluate whether the BD Ultra-Fine™ Nano 4mm x 32 Gauge(G) pen needle manufactured by Becton, Dickinson and Company (BD) provides equivalent glucose control (as measured by hemoglobin A1c levels) as the BD Ultra-Fine™ 8mm x 31G and the BD Ultra-Fine™ 12.7mm x 29G pen needles in obese subjects with diabetes.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2	Device: 4 mm x 32G Pen Needle; Device: 8mm x 31G Pen Needle; Device: 12.7mm x 29G Pen Needle	N/A

Detailed Description

Each subject's participation is expected to last a total of 7 months and includes a screening visit, a three-week wash-in period (one week with each of the three different size pen needles) followed by two consecutive 12 week study periods. The purpose of the three week wash-in period is to minimize the number of dropouts during the following study periods by ensuring that subjects have experience using each of the three study needles and find them generally acceptable for use during the study.

Only subjects who complete the wash-in period and confirm their agreement to continue participating will be randomized into one of the two study arms. Subjects will be randomly assigned to use the BD Ultra-Fine™ 4mm pen needle and either the BD Ultra-Fine™ 8mm pen needle or the BD Ultra-Fine™ 12.7mm pen needle. The randomization will also specify which of the two study pen needles to be used first. Half of the study subjects will use the BD Ultra-Fine™ 4mm and BD Ultra-Fine™ 8mm pen needles (4mm/8mm arm) and the other half will use the BD Ultra-Fine™ 4mm and the BD Ultra-Fine™ 12.7mm pen needles (4mm/12.7mm arm). At the end of the first 12 week study period subjects will switch to the other assigned pen needle for the second and final study period.

Glycemic control (based on HbA1c concentrations) will be assessed at baseline and at the end of each 12 week study period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 293 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: Comparison of Glycemic Control in Obese Subjects With Diabetes Using the BD Ultra-Fine™ Nano 4mm x 32G Pen Needle, and Either the BD Ultra-Fine™ Short 8mm x 31G Pen Needle or the BD Ultra Fine™ 12.7mm x 29G Pen Needle
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 4 mm vs. 8 mm Subjects randomized to this study arm first used either the 4 mm x 32G Pen Needle or the 8mm x 31G Pen Needle for 12 weeks (Period 1), then switched to the alternate pen needle (PN) for another 12 weeks (Period 2). Order of PN use was randomly determined.	Device: 4 mm x 32G Pen Needle; During the 12 week study period, subjects use this pen needle with their own pen device for all daily insulin injections they usually administered themselves with a pen device. Subjects follow their usual insulin regimen and there is no upper limit on total daily insulin dosage or number of injections. Subjects are advised to inject straight in when using the 4mm PN, with no pinch up.; Other Names: BD Ultra-Fine™ Nano pen needle, Catalog number 320122 ; Device: 8mm x 31G Pen Needle; During the 12 week study period, subjects will use this pen needle with their own pen device for all daily insulin injections they usually administered themselves with a pen device. Subjects follow their usual insulin regimen and there is no upper limit on total daily insulin dosage or number of injections. Subjects are directed to use pinch-up when injecting in the abdomen or thigh with the 8mm PN, and no pinch-up at other injection sites.; Other Names: BD Ultra-Fine™ Short pen needle, Catalog number 320109
Experimental: 4 mm vs. 12.7 mm Subjects randomized to this study arm first used either the 4 mm x 32G Pen Needle or the 12.7mm x 29G Pen Needle (PN) for 12 weeks (Period 1), then switched to the alternate PN for another 12 weeks (Period 2). Order of PN use was randomly determined.	Device: 4 mm x 32G Pen Needle; During the 12 week study period, subjects use this pen needle with their own pen device for all daily insulin injections they usually administered themselves with a pen device. Subjects follow their usual insulin regimen and there is no upper limit on total daily insulin dosage or number of injections. Subjects are advised to inject straight in when using the 4mm PN, with no pinch up.; Other Names: BD Ultra-Fine™ Nano pen needle, Catalog number 320122 ; Device: 12.7mm x 29G Pen Needle; During the 12 week study period, subjects will use this pen needle with their own pen device for all daily insulin injections they usually administered themselves with a pen device. Subjects follow their usual insulin regimen and there is no upper limit on total daily insulin dosage or number of injections. When using the 12.7mm PN, subjects are instructed to insert either at an angle of 45 degrees, or to pinch up and hold the pen device at a 90 degree angle (straight in).; Other Names: BD Ultra-Fine™ Original pen needle, BD Catalog Number 328203

Outcome Measures

Primary Outcome Measures

1. Glycemic Control as Measured by HbA1c (4 mm vs. 8 mm) [Over each 12 week study period]

   Subjects' glycemic control was assessed by comparing hemoglobin A1c (HbA1c) levels measured at the end of each 12 week Study Period (e.g., at Visit 5 or Visit 7) to the HbA1c measured at the start of that Study Period, i.e. the baseline (Visit 3) for Period 1 and the Period 1/2 crossover (Visit 5) for Period 2. Analysis included only subjects with HbA1C values at baseline (Visit 3) and at the end of Study Period 1 (Visit 5) and end of Period 2 (Visit 7).

2. Glycemic Control as Measured by HbA1c (4 mm vs. 12.7 mm) [Over each 12 week study period]

   Subjects' glycemic control was assessed by comparing hemoglobin A1c (HbA1c) levels measured at the end of each 12 week Study Period (e.g., at Visit 5 or Visit 7) to the HbA1c measured at the start of that Study Period, i.e. the baseline (Visit 3) for Period 1 and the Period 1/2 crossover (Visit 5) for Period 2. Analysis included only subjects with HbA1C values at baseline (Visit 3) and at the end of Study Period 1 (Visit 5) and end of Period 2 (Visit 7).

Secondary Outcome Measures

1. Glycemic Control as Measured by HbA1c, in High Dose Insulin (at Least One Dose of ≥ 40 Units) Users [Subjects were randomly assigned to use the BD Ultra-Fine™ 4mm pen needle for one - 12 week study period and either the BD Ultra-Fine™ 8mm pen needle or the BD Ultra-Fine™ 12.7mm pen needle for one - 12 week study period.]

   Glycemic control was assessed as by difference between the subjects' HbA1c (%) at baseline (randomization, Visit 3) and at the end of each 12 week study period,in the same manner as for the primary outcome measures. The 95% confidence interval for the mean difference in HbA1c values between the 4mm PN and the longer PN will be estimated based on general linear models adjusting for baseline HbA1c.

2. Injection Pain Scores (4 mm vs. 8 mm) [At the end of Study Period 2]

   At the end of second study period, subjects were asked to rate the level of pain experienced with study period 2 needle compared to the pen needle used in study period 1, using a 150 mm Visual Analog Scale (VAS). The VAS is a measure of the pain perceived with the needle they are using at that point in the study relative to the needle they used in Period 1. The VAS is anchored at the center (0mm) with "as painful" and at each extreme with "much less painful (-75mm) and "much more painful (+75mm); therefore a pain rating < 0 indicates that the Period 2 needle was perceived as less painful than the Period 1 needle.

3. Injection Pain Scores (4 mm vs. 12 mm) [At the end of Study Period 2]

   At the end of second study period, subjects were asked to rate the level of pain experienced with study period 2 needle compared to the pen needle used in study period 1, using a 150 mm Visual Analog Scale (VAS). The VAS is a measure of the pain perceived with the needle they are using at that point in the study relative to the needle they used the previous period. The VAS is anchored at the center (0mm) with "as painful" and at each extreme with "much less painful (-75mm) and "much more painful (+75mm); therefore a negative pain rating means the period 2 needle was perceived as less painful than the period 1 needle.

4. Number of Serious, Unexplained Hypoglycemic Events, Reported as Number of Events by Needle. [During Study Period 1 (12 weeks) and Study Period 2 (12 weeks)]

   Subjects were asked to record hypoglycemic events in his/her diary anytime his/her blood glucose (BG) was below 50mg/dL, s/he had signs/symptoms of hypoglycemia, or s/he required medical attention for treatment. Hypoglycemia was defined as serious when the subject required the assistance of another person to be treated, or when the hypoglycemic event met the per-protocol definition of a Serious Adverse Event. An unexplained episode was defined as one with no known cause (for example, the subject skipped a meal or exercised vigorously).

5. Number of Serious, Unexplained Hyperglycemic Events, Reported as Number of Events by Needle. [During Study Period 1 (12 weeks) and Study Period 2 (12 weeks)]

   Subjects were asked to record hyperglycemic events in his/her diary anytime his/her blood glucose (BG) was above 400mg/dL, or s/he required medical attention for treatment for hyperglycemia. Hyperglycemia was defined as serious when the subject required the assistance of another person to be treated, or when the hyperglycemic event met the per-protocol definition of a Serious Adverse Event. An unexplained episode was defined as one with no known cause (for example, the subject missed an insulin dose). Subjects were asked to record these events in a diary.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Insulin requiring diabetics (type 1 or type 2)

• Using a pen device for self-injection of all diabetes-related medications for at least two months prior to screening.

• 18 to 80 years of age, inclusive.

• Body Mass Index of at least 30 kg/m².

• Hemoglobin A1c from 5.5 to 9.5 percent (%), inclusive.

• Self-monitor blood glucose at least twice per day with a memory blood glucose meter, and willing to do so at least twice per day for the duration of the study

• On a stable diabetes treatment regimen (for example, no change to non-insulin therapies)for at least 2 months prior to screening

• Able to read, write and follow instructions in English or Spanish.

Exclusion Criteria:

• Administer insulin with a pump.

• Currently use a syringe to inject insulin or any other diabetes-related medication.

• Pregnancy.

• History of intravenous drug abuse.

• Current status or history of a medical condition that would contraindicate treatment with the study product or other conditions which, in the opinion of the Investigator, would place the subject at risk or have the potential to confound interpretation of the study results (i.e. recent history of ketoacidosis, hypoglycemic unawareness, etc.)

• Participated in any one of the following clinical studies:

• BDDC-08-011, 'Comparison of Glycemic Control among Diabetics using the 4mm x 32G BD Pen Needle versus the 8mm x 31G BD Pen Needle and the 5mm x 31G BD Pen Needle'.

• DBC-10-SQUIR04, 'Evaluation of Glycemic Control and User Acceptability of the BD Ultrafine Nano 4mm x 32G Pen Needle for Injection of Long-Acting or Basal Insulin Doses Above 40 Units'

• DBC-10-EMRLD01, 'Design Validation of BD 5-bevel Pen Needles (4,5 and 8mm) in Subjects with Diabetes'

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AMCR Institute, Inc.	Escondido	California	United States	92026
2	Atlanta Diabetes Associates	Atlanta	Georgia	United States	30309
3	Springfield Diabetes and Endocrine Center	Springfield	Illinois	United States	62704
4	International Diabetes Center (IDC)	Minneapolis	Minnesota	United States	55416
5	Diabetes and Endocrine Associates	Omaha	Nebraska	United States	68131
6	The Molly Diabetes Center for Adults and Children at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
7	Mountain Diabetes and Endocrine Center	Asheville	North Carolina	United States	28803
8	University Diabetes and Endocrine Consultants	Chattanooga	Tennessee	United States	37403
9	Clinical Trials of Texas, Inc	San Antonio	Texas	United States	78229
10	Corporate Lane Internal Medicine and Research Center	Virgina Beach	Virginia	United States	23462

Sponsors and Collaborators

• Becton, Dickinson and Company

Investigators

• Study Director: Laurence Hirsch, MD, BD Medical - Diabetes Care

Study Documents (Full-Text)

None provided.

More Information

Publications

• Gibney MA, Arce CH, Byron KJ, Hirsch LJ. Skin and subcutaneous adipose layer thickness in adults with diabetes at sites used for insulin injections: implications for needle length recommendations. Curr Med Res Opin. 2010 Jun;26(6):1519-30. doi: 10.1185/03007995.2010.481203.

• Responsible Party: Becton, Dickinson and Company
• ClinicalTrials.gov Identifier: NCT01231984
• Other Study ID Numbers: DBC-10-SQUIR05
• First Posted: Nov 2, 2010
• Last Update Posted: Jun 27, 2014
• Last Verified: May 1, 2014

• Keywords provided by Becton, Dickinson and Company: diabetes; obesity; hypoglycemia; hyperglycemia; pen needle
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1

Study Results

Participant Flow

Recruitment Details	A total of 380 subjects were screened from the current diabetic patient population at 10 research centers in the US. Of those, 293 subjects met eligibility criteria and were enrolled in the wash-in period.
Pre-assignment Detail	Subjects who successfully completed the wash-in period and agreed to participate were further randomized into one of the study arms. Specifically, 274 of 293 subjects who were enrolled in the wash-in period completed the wash-in period and were randomized into one of the two study arms.

Arm/Group Title	4 mm First (4 vs.8)	8 mm First (4 vs.8)	4 mm First (4 vs.12.7)	12.7 mm First ( 4 vs.12.7)
Arm/Group Description	Subjects randomized to this sequence used the 4mm PN for the first 12 weeks (Period 1), then switched to the 8 mm PN for the next 12 weeks (Period 2).	Subjects randomized to this sequence used the 8mm PN for the first 12 weeks (Period 1), then switched to the 4 mm PN for the next 12 weeks (Period 2).	Subjects randomized to this sequence used the 4mm PN for the first 12 weeks (Period 1), then switched to the 12.7 mm PN for the next 12 weeks (Period 2).	Subjects randomized to this sequence used the 12.7 mm PN for the first 12 weeks (Period 1), then switched to the 4 mm PN for the next 12 weeks (Period 2).
Period Title: Study Period 1
STARTED	69	70	66	69
COMPLETED	57	63	59	60
NOT COMPLETED	12	7	7	9
Period Title: Study Period 1
STARTED	57	63	59	60
COMPLETED	54	61	59	56
NOT COMPLETED	3	2	0	4

Baseline Characteristics

Arm/Group Title	4 mm vs. 8 mm	4 mm vs. 12.7 mm	Total
Arm/Group Description	Subjects randomized to this study arm first use either the 4mm PN or the 8mm PN for 12 weeks, then switched to the alternate PN for another 12 weeks. Order of PN use is randomly determined.	Subjects randomized to this study arm first use either the 4mm PN or the 12.7mm PN for 12 weeks, then switch to the alternate PN for another 12 weeks. Order of PN use is randomly determined.	Total of all reporting groups
Overall Participants	139	135	274
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.5 (10.6)	55.9 (11.3)	56.7 (11.0)
Sex: Female, Male (Count of Participants)
Female	66 47.5%	66 48.9%	132 48.2%
Male	73 52.5%	69 51.1%	142 51.8%
Region of Enrollment (participants) [Number]
United States	139 100%	135 100%	274 100%

Outcome Measures

1. Primary Outcome

Title	Glycemic Control as Measured by HbA1c (4 mm vs. 8 mm)
Description	Subjects' glycemic control was assessed by comparing hemoglobin A1c (HbA1c) levels measured at the end of each 12 week Study Period (e.g., at Visit 5 or Visit 7) to the HbA1c measured at the start of that Study Period, i.e. the baseline (Visit 3) for Period 1 and the Period 1/2 crossover (Visit 5) for Period 2. Analysis included only subjects with HbA1C values at baseline (Visit 3) and at the end of Study Period 1 (Visit 5) and end of Period 2 (Visit 7).
Time Frame	Over each 12 week study period

Outcome Measure Data

Analysis Population Description

115 subjects completed all main study visits. Two subjects were excluded from the 4 vs. 8 primary analysis due to protocol deviations. The total population size evaluated for the primary objective (4 vs. 8) is therefore 113.

Arm/Group Title	4 mm First (4 vs. 8)	8 mm First (4 vs. 8)
Arm/Group Description	Subjects randomized to this sequence used the 4mm PN for the first 12 weeks (Period 1), then switched to the 8 mm PN for the next 12 weeks (Period 2).	Subjects randomized to this sequence used the 8mm PN for the first 12 weeks (Period 1), then switched to the 4 mm PN for the next 12 weeks (Period 2).
Measure Participants	54	59
HbA1c at baseline (Visit 3)	7.59 (0.86)	7.46 (1.01)
HbA1c end of Period 1 (Visit 5)	7.63 (0.92)	7.59 (1.28)
HbA1c end of Period 2 (Visit 7)	7.78 (1.23)	7.59 (1.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	4 mm First (4 vs. 8), 8 mm First (4 vs. 8)
	Comments	General linear models with baseline as a covariate, needle type, period, and randomization sequence as fixed effects, and subject as random effect were fit to the data.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Two one-sided 95% confidence limits for the difference in HbA1c between the 4mm PN and the 8mm PN was calculated. Equivalence limits for HbA1C were defined a-priori as +/- 0.4% units.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Effect of 4mm versus 8mm PN on HbA1c
	Estimated Value	-0.076
	Confidence Interval	(2-Sided) 95%; -0.209 to 0.058
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Glycemic Control as Measured by HbA1c, in High Dose Insulin (at Least One Dose of ≥ 40 Units) Users
Description	Glycemic control was assessed as by difference between the subjects' HbA1c (%) at baseline (randomization, Visit 3) and at the end of each 12 week study period,in the same manner as for the primary outcome measures. The 95% confidence interval for the mean difference in HbA1c values between the 4mm PN and the longer PN will be estimated based on general linear models adjusting for baseline HbA1c.
Time Frame	Subjects were randomly assigned to use the BD Ultra-Fine™ 4mm pen needle for one - 12 week study period and either the BD Ultra-Fine™ 8mm pen needle or the BD Ultra-Fine™ 12.7mm pen needle for one - 12 week study period.

Outcome Measure Data

Analysis Population Description

Of the 226 subjects who were considered for the Primary analysis, 107 subjects had at least one dose of insulin that was at least 40 units. The glycemic control of this sub-group of subjects was analyzed as in the Primary Analysis.The same analysis was performed for the high insulin dose subjects, with the two longer PN study arms pooled together.

Arm/Group Title	4 mm First	Longer PN First (8mm or 12.7mm)
Arm/Group Description	Subjects in this group first used the 4 mm PN for 12 weeks in Period 1, then switched to a longer PN (8 mm or 12 mm PN) for another 12 weeks in Period 2, based on their randomization.	Subjects in this group first used one of the longer PNs (8 mm or 12 mm PN) for 12 weeks in Period 1, based on the randomization, then switched to the 4mm PN for another 12 weeks in Period 2.
Measure Participants	52	55
HbA1c at Baseline (Visit 3)	7.77 (0.92)	7.57 (0.90)
HbA1c end Period 1 (Visit 5)	7.76 (1.03)	7.62 (0.97)
HbA1c end Period 2 (Visit 7)	7.98 (1.35)	7.66 (0.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	4 mm First (4 vs. 8), 8 mm First (4 vs. 8)
	Comments	General linear models with baseline as a covariate, needle type, period, and randomization sequence as fixed effects, and subject as random effect were fit to the data.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Two one-sided 95% confidence limits for the difference in HbA1c between the 4 mm PN and the longer PNs (pooled) was calculated. Equivalence limits for HbA1c were defined a-priori as +/- 0.4% units.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Effect of 4mm PN vs. longer PN on HbA1c
	Estimated Value	-0.090
	Confidence Interval	(2-Sided) 95%; -0.23 to 0.051
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Injection Pain Scores (4 mm vs. 8 mm)
Description	At the end of second study period, subjects were asked to rate the level of pain experienced with study period 2 needle compared to the pen needle used in study period 1, using a 150 mm Visual Analog Scale (VAS). The VAS is a measure of the pain perceived with the needle they are using at that point in the study relative to the needle they used in Period 1. The VAS is anchored at the center (0mm) with "as painful" and at each extreme with "much less painful (-75mm) and "much more painful (+75mm); therefore a pain rating < 0 indicates that the Period 2 needle was perceived as less painful than the Period 1 needle.
Time Frame	At the end of Study Period 2

Outcome Measure Data

Analysis Population Description

115 subjects in the 4mm vs. 8 mm study arm completed all main study visits. Two of the 115 subjects were excluded from all primary and secondary analyses due to protocol deviations. The total number of subjects analyzed for perceived pain for this study was therefore 113.

Arm/Group Title	4 mm Among Those in 8mm x 4 mm Arm	8 mm Among Those in 4mm x 8mm Arm
Arm/Group Description	Subjects randomized to this study arm first used the 8mm PN for 12 weeks, then switched to the 4mm PN for another 12 weeks.	Subjects randomized to this study arm first used the 4mm PN for 12 weeks, then switched to the 8mm PN for another 12 weeks.
Measure Participants	59	54
Mean (Standard Error) [mm]	-31.53 (5.3)	-19.17 (4.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	4 mm First (4 vs. 8), 8 mm First (4 vs. 8)
	Comments	Subjects rated the level of pain experienced when using the PN assigned for use during Study Period 2 compared to the PN assigned for use in Study Period 1. By placing a mark on a line, whose midpoint(anchor) was designated as 0, and represented "equivalent pain with assigned PNs", ratings on the continuum represented the degree to which the PN used in the second Study Period was less than or greater than the PN used during the first Study Period.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	p< 0.05 was considered statistically significant in this study
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	12.36
	Confidence Interval	(1-Sided) 95%; 0.37 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Injection Pain Scores (4 mm vs. 12 mm)
Description	At the end of second study period, subjects were asked to rate the level of pain experienced with study period 2 needle compared to the pen needle used in study period 1, using a 150 mm Visual Analog Scale (VAS). The VAS is a measure of the pain perceived with the needle they are using at that point in the study relative to the needle they used the previous period. The VAS is anchored at the center (0mm) with "as painful" and at each extreme with "much less painful (-75mm) and "much more painful (+75mm); therefore a negative pain rating means the period 2 needle was perceived as less painful than the period 1 needle.
Time Frame	At the end of Study Period 2

Outcome Measure Data

Analysis Population Description

115 subjects in the 4mm vs. 12 mm study arm completed all main study visits. One of the subjects was excluded from all primary and secondary analyses due to protocol deviations.

Arm/Group Title	4 mm Among Those in 12mm x 4mm Arm	12 mm Among Those in 4 mm x 12 mm Arm
Arm/Group Description	Subjects randomized to this study arm first used the 12mm PN for 12 weeks, then switched to the 4mm PN for another 12 weeks.	Subjects randomized to this study arm first used the 4mm PN for 12 weeks, then switched to the 12mm PN for another 12 weeks.
Measure Participants	56	58
Mean (Standard Error) [mm]	-27.72 (5.47)	3.10 (5.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	4 mm First (4 vs. 8), 8 mm First (4 vs. 8)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	p< 0.05 was considered statistically significant in this study.
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	30.83
	Confidence Interval	(1-Sided) 95%; 18.54 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Serious, Unexplained Hypoglycemic Events, Reported as Number of Events by Needle.
Description	Subjects were asked to record hypoglycemic events in his/her diary anytime his/her blood glucose (BG) was below 50mg/dL, s/he had signs/symptoms of hypoglycemia, or s/he required medical attention for treatment. Hypoglycemia was defined as serious when the subject required the assistance of another person to be treated, or when the hypoglycemic event met the per-protocol definition of a Serious Adverse Event. An unexplained episode was defined as one with no known cause (for example, the subject skipped a meal or exercised vigorously).
Time Frame	During Study Period 1 (12 weeks) and Study Period 2 (12 weeks)

Outcome Measure Data

Analysis Population Description

Two hundred seventy-four subjects were randomized into the study. Data from all subjects randomized were included in the analysis of subjects with serious, unexplained hypoglycemic events.

Arm/Group Title	4mm Needle	8mm Needle	12.7mm Needle
Arm/Group Description	Number of subjects enrolled who were assigned to use the 4mm PN.	Number of subjects enrolled who were assigned to use the 8mm PN.	Number of subjects enrolled who were assigned to use the 12.7mm PN.
Measure Participants	274	139	135
Number [Adverse Events]	1	2	0

6. Primary Outcome

Title	Glycemic Control as Measured by HbA1c (4 mm vs. 12.7 mm)
Description	Subjects' glycemic control was assessed by comparing hemoglobin A1c (HbA1c) levels measured at the end of each 12 week Study Period (e.g., at Visit 5 or Visit 7) to the HbA1c measured at the start of that Study Period, i.e. the baseline (Visit 3) for Period 1 and the Period 1/2 crossover (Visit 5) for Period 2. Analysis included only subjects with HbA1C values at baseline (Visit 3) and at the end of Study Period 1 (Visit 5) and end of Period 2 (Visit 7).
Time Frame	Over each 12 week study period

Outcome Measure Data

Analysis Population Description

115 subjects completed all main study visits. Two subjects were excluded from the 4 vs. 12.7 primary analysis due to protocol deviations. The total population size evaluated for this analysis is therefore 113.

Arm/Group Title	4 mm First (4 vs. 12.7)	12.7 mm First (4 vs. 12.7)
Arm/Group Description	Subjects randomized to this sequence used the 4mm PN for the first 12 weeks (Period 1), then switched to the 12.7 mm PN for the next 12 weeks (Period 2).	Subjects randomized to this sequence used the 12.7 mm PN for the first 12 weeks (Period 1), then switched to the 4 mm PN for the next 12 weeks (Period 2).
Measure Participants	57	56
HbA1c Baseline (Visit 3)	7.57 (0.96)	7.45 (0.88)
HbA1c end of Period 1 (Visit 5)	7.58 (1.03)	7.54 (0.95)
HbA1c end of Period 2 (Visit 7)	7.73 (1.18)	7.51 (0.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	4 mm First (4 vs. 8), 8 mm First (4 vs. 8)
	Comments	General linear models with baseline as a covariate, needle type, period, and randomization sequence as fixed effects, and subject as random effect were fit to the data.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Two one-sided 95% confidence limits for the difference in HbA1c between the 4mm PN and the 12.7mm PN was calculated. Equivalence limits for HbA1C were defined a-priori as +/- 0.4% units
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Effect of 4 mm vs.12.7mm PN on HbA1c
	Estimated Value	- 0.095
	Confidence Interval	(2-Sided) 95%; -0.190 to -0.000
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Serious, Unexplained Hyperglycemic Events, Reported as Number of Events by Needle.
Description	Subjects were asked to record hyperglycemic events in his/her diary anytime his/her blood glucose (BG) was above 400mg/dL, or s/he required medical attention for treatment for hyperglycemia. Hyperglycemia was defined as serious when the subject required the assistance of another person to be treated, or when the hyperglycemic event met the per-protocol definition of a Serious Adverse Event. An unexplained episode was defined as one with no known cause (for example, the subject missed an insulin dose). Subjects were asked to record these events in a diary.
Time Frame	During Study Period 1 (12 weeks) and Study Period 2 (12 weeks)

Outcome Measure Data

Analysis Population Description

Two hundred seventy-four subjects were randomized into the study. Data from all subjects randomized were included in the analysis of subjects with serious, unexplained hyperglycemic events.

Arm/Group Title	4mm Needle	8mm Needle	12.7mm Needle
Arm/Group Description	Number of subjects enrolled who were assigned to use the 4mm PN.	Number of subjects enrolled who were assigned to use the 8mm PN.	Number of subjects enrolled who were assigned to use the 12.7mm PN.
Measure Participants	274	139	135
Number [Adverse Events]	0	0	0

Adverse Events

Time Frame	Adverse events that occurred during the wash-in period as well as during the two study periods were collected throughout each subject's participation in the study. Total time of participation could have been up to approximately eight months.
Arm/Group Title	4mm Needle		8mm Needle		12.7mm Needle
Arm/Group Description
All Cause Mortality
	4mm Needle		8mm Needle		12.7mm Needle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	4mm Needle		8mm Needle		12.7mm Needle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/274 (3.3%)		1/127 (0.8%)		7/147 (4.8%)
Cardiac disorders
Heart Failure NEC	1/274 (0.4%)	1	0/127 (0%)	0	0/147 (0%)	0
Ischaemic Coronary Artery Disorders	1/274 (0.4%)	1	0/127 (0%)	0	0/147 (0%)	0
Ear and labyrinth disorders
Inner Ear Signs and Symptoms	1/274 (0.4%)	1	0/127 (0%)	0	0/147 (0%)	0
Gastrointestinal disorders
Diaphragmatic Hernias	1/274 (0.4%)	1	0/127 (0%)	0	0/147 (0%)	0
Gastric and Gastroenteric Infections	1/274 (0.4%)	1	0/127 (0%)	0	0/147 (0%)	0
Gastrointestinal and Abdominal Pains (Excl Oral and Throat)	0/274 (0%)	0	0/127 (0%)	0	1/147 (0.7%)	2
Intestinal Ulceration and Perforation	1/274 (0.4%)	1	0/127 (0%)	0	0/147 (0%)	0
Nausea and Vomiting Symptoms	1/274 (0.4%)	1	0/127 (0%)	0	0/147 (0%)	0
Infections and infestations
Lower Respiratory Tract and Lung Infections	0/274 (0%)	0	0/127 (0%)	0	1/147 (0.7%)	1
Injury, poisoning and procedural complications
Lower Limb Fractures and Dislocations	1/274 (0.4%)	1	0/127 (0%)	0	0/147 (0%)	0
Non-Site Specific Injuries	0/274 (0%)	0	0/127 (0%)	0	1/147 (0.7%)	1
Metabolism and nutrition disorders
Diabetic Complications Opthalmic	1/274 (0.4%)	1	0/127 (0%)	0	0/147 (0%)	0
General Nutritional Disorder	0/274 (0%)	0	0/127 (0%)	0	1/147 (0.7%)	1
Hypoglycaemic Conditions NEC	1/274 (0.4%)	1	0/127 (0%)	0	0/147 (0%)	0
Musculoskeletal and connective tissue disorders
Joint Related Signs and Symptoms	1/274 (0.4%)	1	0/127 (0%)	0	0/147 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic Neoplasms Malignant (Excl Islet Cell and Carcinoid)	0/274 (0%)	0	0/127 (0%)	0	1/147 (0.7%)	1
Prostate Neoplasms Malignant	0/274 (0%)	0	0/127 (0%)	0	1/147 (0.7%)	1
Thyroid Neoplasms Malignant	0/274 (0%)	0	1/127 (0.8%)	1	0/147 (0%)	0
Renal and urinary disorders
Urinary Abnormalities	0/274 (0%)	0	0/127 (0%)	0	1/147 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Lower Respiratory Tract Infection NEC	1/274 (0.4%)	1	0/127 (0%)	0	0/147 (0%)	0
Other (Not Including Serious) Adverse Events
	4mm Needle		8mm Needle		12.7mm Needle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	91/274 (33.2%)		36/127 (28.3%)		29/147 (19.7%)
Metabolism and nutrition disorders
Hypoglycaemic Conditions NEC	60/274 (21.9%)	209	25/127 (19.7%)	91	20/147 (13.6%)	83
Hyperglycaemic Conditions NEC	17/274 (6.2%)	63	8/127 (6.3%)	20	7/147 (4.8%)	30
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Infections NEC	14/274 (5.1%)	14	3/127 (2.4%)	3	2/147 (1.4%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The PI and Clinical Center will not publish the results pursuant to the Protocol without sponsor review and opportunity to comment on the publication or oral presentation. Abstracts and synopsis of oral presentations must be received by sponsor 30 days, and journal submissions 60 days, prior to submission. The data generated pursuant to the Protocol will be the property of the sponsor and may be used in any manner by the sponsor as it may determine in its sole discretion.