Comparison of Glycemic Control Among Diabetics Using Three Different Pen Needles

Study Overview
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Brief Summary
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Anxiety about needles is a commonly expressed concern by diabetics about beginning insulin therapy. A shorter, thinner pen needle that delivers insulin with the safety and efficacy profile of currently marketed pen needles may appeal to many diabetic patients as the new needle may be perceived as less intimidating and more comfortable. Currently marketed pen needles range in length from 5 to 12.7 millimeters (mm). The primary purpose of this study was to evaluate whether the investigational 4mm x 32 Gauge(G) pen needle manufactured by Becton, Dickinson and Company (BD) provides equivalent glucose control (as measured by fructosamine levels) as the currently marketed BD 5mm x 31 G and BD 8mm x 31 G pen needles (PN)in diabetic subjects with varying insulin dosage regimens.

Detailed Description
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Within each dose group, subjects were randomly assigned at baseline to one of two study arms. One study arm (4/5 mm PN) compared the BD 4mm PN to the 5mm PN, and the other arm (4/8 mm PN) compared the BD 4mm PN to the 8mm PN, in a crossover fashion. Based on the randomization, subjects used either the 4mm or the other assigned PN (5mm or 8mm) for the first 3 weeks, then switched to the alternate PN for the next 3 weeks. Glycemic control was assessed by serum fructosamine (FRU) levels at the end of each 3 week period. Based on their baseline insulin regimen, subjects were also assigned to an insulin dosing group (Low or Regular) to help ensure balance among treatment arms. Requirements for each group were as follows: Low Dose: largest single dose of insulin each day with a pen device must be less than or equal to 20 units. Regular Dose: largest single dose of insulin each day, with a pen device, must be 21-40 units. Explanation of Visits and Timing of Assessments: Visit 1: Screening Informed Consent Demographics Inclusion /Exclusion Hemoglobin A1c measurement (HbA1c) Visit 2 (Baseline:) Insulin dose group assignment (Low dose or Regular dose) Randomization Fructosamine blood sample collected Dispense pen needle (PN) assigned first Visit 3 (approximately 3 weeks after starting first PN) Pain rated by subject relative to baseline PN Review Adverse Events (AEs) and reported events of injection site leakage Fructosamine blood sample collected Dispense second assigned PN Visit 4 (approximately 3 weeks after starting second PN): Review AEs and reported events of injection site leakage Fructosamine blood sample collected Pain rated relative to previously used PN Study Completion

Official Title
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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

Conditions
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Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Device: 4mm x 32G pen needle
* Device: 8mm x 31G pen needle
* Device: 5mm x 31G pen needle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Insulin requiring diabetics (type 1 or type 2) Using a pen device for injections at least once per day, for at least two months prior to baseline (Study Visit Two). 18 to 75 years of age, inclusive. Body Mass Index from 18 to 50 kg/m², inclusive. Hemoglobin A1c from 5.5 to 9.5 percent (%), inclusive. Largest single dose of insulin a day less than or equal to 40 units Exclusion Criteria: 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.). Hemophilia or any other disorder which causes excessive bleeding or requires frequent transfusions. History of intravenous drug abuse (self-reported). Bleeding disorder, hemophilia or subject is currently taking anti-coagulant medications (e.g., heparin, Coumadin®, warfarin). Self-reported blood borne infection. Pregnant (from medical history only).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4 mm / 8 mm PN<br>Subjects randomized to this study arm used either the 4mm PN or the 8mm PN for 3 weeks, then switched to the alternate PN for another 3 weeks. Order of PN use was randomly determined. | Device: 4mm x 32G pen needle<br>* For 3 weeks, subjects used this pen needle with their own pen device for all daily insulin injections they usually administered themselves with a pen device. Subjects followed their usual insulin regimen and there was no upper limit on total daily insulin dosage or number of injections. Subjects were advised to inject straight in when using the 4mm PN, with no pinch up.<br>* Other names: BD Ultra-Fine™ Nano pen needle, Catalog number 320122;Device: 8mm x 31G pen needle<br>* For 3 weeks, subjects used this pen needle with their own pen device for all daily insulin injections they usually administered themselves with a pen device. Subjects followed their usual insulin regimen and there was no upper limit on total daily insulin dosage or number of injections. Subjects were directed to use pinch-up when injecting in the abdomen or thigh with the 8mm PN, and no pinch-up at other injection sites.<br>* Other names: BD Ultra-Fine™ Short pen needle, Catalog number 320109;|
| Experimental: 4 mm / 5 mm PN<br>Subjects randomized to this study arm used either the 4mm PN or the 5mm PN for 3 weeks, then switched to the alternate PN for another 3 weeks. Order of PN use was randomly determined. | Device: 4mm x 32G pen needle<br>* For 3 weeks, subjects used this pen needle with their own pen device for all daily insulin injections they usually administered themselves with a pen device. Subjects followed their usual insulin regimen and there was no upper limit on total daily insulin dosage or number of injections. Subjects were advised to inject straight in when using the 4mm PN, with no pinch up.<br>* Other names: BD Ultra-Fine™ Nano pen needle, Catalog number 320122;Device: 5mm x 31G pen needle<br>* For 3 weeks, subjects used this pen needle with their own pen device for all daily insulin injections they usually administered themselves with a pen device. Subjects followed their usual insulin regimen and there was no upper limit on total daily insulin dosage or number of injections. Subjects were advised to inject straight in when using the 5mm PN, with no pinch up.<br>* Other names: BD Ultra-Fine™ Mini pen needle, Catalog Number 320119;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent (%) Absolute Change in Fructosamine | Within each study arm (4mm / 5mm PN, or 4mm / 8mm PN) subjects used one pen needle (PN) for 3 weeks then switched to the alternate PN for the next three weeks, for a total of 6 weeks. The principal endpoint measure of glycemic control is the percent absolute change in serum fructosamine concentration, based on the fructosamine (FRU) concentration measured in micromoles per liter (umol/L) at the end of each three week period. The change was calculated according to the following formula: Percent absolute change in FRU, or %|∆ FRU|= 100*[FRU(4mm)-FRU(5 or 8mm)]/[FRU(5 or 8mm)]. | 3 weeks per pen needle, from visit 2-3 and visit 3-4. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Absolute Change in Fructosamine, by Dose Group | Glycemic control was determined separately for each insulin dose group in the same manner as described for the primary outcome measure, according to the following formula: %|∆ FRU|= 100*[FRU(4mm)-FRU(5 or 8mm)]/[FRU(5 or 8mm)]. | 3 weeks per pen needle, from visit 2-3 and visit 3-4. | 
| Number of Subjects With Severe Unexplained Hypoglycemic Events | Severe Unexplained Hypoglycemia is defined as an event in which the subject's blood glucose is below 50 milligrams per deciliter (mg/dL) and/or they required assistance from another person for treatment and there is no identified cause (for example, the subject skipped a meal). These events were also reported as Adverse Events. | During 3 weeks using each pen needle | 
| Number of Subjects With Severe Unexplained Hyperglycemic Events | Severe Unexplained Hyperglycemia is defined as requiring a visit to the emergency room or hospitalization and/or having a blood glucose value above 450mg/dL without an identified cause (for example, the subject missed an insulin dose). These events were also reported as Adverse Events. | During 3 weeks using each pen needle | 
| Relative Injection Pain Score Assessed by Subject | After using the second assigned pen needle (PN) for 3 weeks, subjects used a 150mm Visual Analog Scale (VAS) to rate the pain of the second PN relative to the first PN. The VAS was anchored at the center (0mm) with as painful, and at the extreme ends with much less painful (-75mm) and much more painful (+75mm). VAS scores were adjusted for the order of PN use, such that a positive score means that the 4mm PN was scored as more painful than the reference PN (5mm or 8mm), and a negative score indicates that the 4mm PN was less painful than the reference. | Visit 4: 18-24 days after starting 2nd pen needle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pen Needle, Diabetes, Insulin, Glycemic, Pain, Fructosamine, Leakage, Hypoglycemia, Hyperglycemia