Trial Outcomes & Findings for Comparison of Glycemic Control Among Diabetics Using Three Different Pen Needles (NCT NCT00928057)

Last Updated: 2010-10-20

Results Overview

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\*\[FRU(4mm)-FRU(5 or 8mm)\]/\[FRU(5 or 8mm)\].

Recruitment status

COMPLETED

Study phase

Target enrollment

173 participants

Primary outcome timeframe

3 weeks per pen needle, from visit 2-3 and visit 3-4.

Results posted on

2010-10-20

Participant Flow

Subjects were recruited at four independent research centers/diabetes clinics from June 2009 - October 2009

A total of 205 subjects were screened at four sites. Of those, 32 subjects did not satisfy eligibility criteria or withdrew consent prior to using the test products, and the remaining 173 subjects were enrolled and randomized.

Participant milestones

Participant milestones
Measure	4 mm / 8 mm PN This group represents all subjects that were randomized to compare the 4mm and 8mm pen needle (PN) during the study. Each PN was used for 3 consecutive weeks; which PN was used first was based on the subject's randomization assignment.	4 mm / 5 mm PN This group represents all subjects that were randomized to compare the 4mm and 5mm pen needle (PN) during the study. Each PN was used for 3 consecutive weeks; which PN was used first was based on the subject's randomization assignment.
Overall Study STARTED	84	89
Overall Study COMPLETED	82	85
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Reasons for withdrawal
Measure	4 mm / 8 mm PN This group represents all subjects that were randomized to compare the 4mm and 8mm pen needle (PN) during the study. Each PN was used for 3 consecutive weeks; which PN was used first was based on the subject's randomization assignment.	4 mm / 5 mm PN This group represents all subjects that were randomized to compare the 4mm and 5mm pen needle (PN) during the study. Each PN was used for 3 consecutive weeks; which PN was used first was based on the subject's randomization assignment.
Overall Study Adverse Event	1	2
Overall Study Withdrawal by Subject	1	0
Overall Study Lost to Follow-up	0	1
Overall Study Protocol Violation	0	1

Baseline Characteristics

Comparison of Glycemic Control Among Diabetics Using Three Different Pen Needles

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	4 mm / 8 mm PN n=84 Participants This group represents all subjects that were randomized to the study arm comparing the 4 mm and 8 mm pen needles, regardless of whether they completed the study.	4 mm / 5 mm PN n=89 Participants This group represents all subjects that were randomized to the study arm comparing the 4 mm and 5 mm pen needles, regardless of whether they completed the study.	Total n=173 Participants Total of all reporting groups
Age Continuous	51.3 years n=5 Participants	53.8 years n=7 Participants	52.6 years n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	39 Participants n=7 Participants	75 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	50 Participants n=7 Participants	98 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	67 Participants n=5 Participants	66 Participants n=7 Participants	133 Participants n=5 Participants
Race/Ethnicity, Customized Black/African American	10 Participants n=5 Participants	16 Participants n=7 Participants	26 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Diabetes Type Type 1 diabetes	30 Participants n=5 Participants	34 Participants n=7 Participants	64 Participants n=5 Participants
Diabetes Type Type 2 diabetes	54 Participants n=5 Participants	55 Participants n=7 Participants	109 Participants n=5 Participants
Body Mass Index (BMI)	30.1 kg/m² n=5 Participants	30.9 kg/m² n=7 Participants	30.5 kg/m² n=5 Participants
Hemoglobin A1c (HbA1c)	7.4 percent STANDARD_DEVIATION 1.0 • n=5 Participants	7.6 percent STANDARD_DEVIATION 1.0 • n=7 Participants	7.5 percent STANDARD_DEVIATION 1.0 • n=5 Participants
Insulin Dose Group Low Dose	48 participants n=5 Participants	49 participants n=7 Participants	97 participants n=5 Participants
Insulin Dose Group Regular Dose	36 participants n=5 Participants	40 participants n=7 Participants	76 participants n=5 Participants
Single Largest Daily Insulin Dose	19.6 Units n=5 Participants	21.3 Units n=7 Participants	20.5 Units n=5 Participants
Serum Fructosamine Concentration	298.3 umol/L STANDARD_DEVIATION 48.4 • n=5 Participants	301.5 umol/L STANDARD_DEVIATION 61.0 • n=7 Participants	299.9 umol/L STANDARD_DEVIATION 55.1 • n=5 Participants

PRIMARY outcome

Timeframe: 3 weeks per pen needle, from visit 2-3 and visit 3-4.

Population: 167 subjects completed the study. 163 of the 167 completed subjects were included in this analysis. Four (4) of 167 were excluded due to out of window fructosamine samples (3), or laboratory error with fructosamine sample (1).

Outcome measures

Outcome measures
Measure	4 mm / 8 mm PN n=80 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	4 mm / 5 mm PN n=83 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	8 mm PN All randomized subjects that used the 8mm PN, either during the first or second 3 weeks of the study.
Percent (%) Absolute Change in Fructosamine	5.5 Percent absolute change Interval 4.5 to 6.4	4.9 Percent absolute change Interval 3.8 to 6.0	—

SECONDARY outcome

Timeframe: 3 weeks per pen needle, from visit 2-3 and visit 3-4.

Population: 4 of the 167 completed subjects were excluded for out of window fructosamine samples (3), or lab error with a sample (1). For 4 mm/8 mm: this includes 45 subjects in the Low Dose insulin group and 35 in the Regular Dose group. For 4 mm/5 mm: this includes 47 subjects in the Low Dose insulin group and 36 in the Regular 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\*\[FRU(4mm)-FRU(5 or 8mm)\]/\[FRU(5 or 8mm)\].

Outcome measures

Outcome measures
Measure	4 mm / 8 mm PN n=80 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	4 mm / 5 mm PN n=83 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	8 mm PN All randomized subjects that used the 8mm PN, either during the first or second 3 weeks of the study.
Percent Absolute Change in Fructosamine, by Dose Group Low Insulin Dose Group	5.5 Percent absolute change Interval 4.4 to 6.7	5.5 Percent absolute change Interval 3.7 to 7.2	—
Percent Absolute Change in Fructosamine, by Dose Group Regular Insulin Dose Group	5.3 Percent absolute change Interval 3.7 to 7.0	4.2 Percent absolute change Interval 3.0 to 5.3	—

SECONDARY outcome

Timeframe: During 3 weeks using each pen needle

Population: All subjects that were randomized and used at least one of the study pen needles are included. The number of subjects with one or more events while using each PN is presented.

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.

Outcome measures

Outcome measures
Measure	4 mm / 8 mm PN n=173 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	4 mm / 5 mm PN n=89 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	8 mm PN n=84 Participants All randomized subjects that used the 8mm PN, either during the first or second 3 weeks of the study.
Number of Subjects With Severe Unexplained Hypoglycemic Events	5 participants	5 participants	4 participants

SECONDARY outcome

Timeframe: During 3 weeks using each pen needle

Population: All subjects that were randomized and used at least one of the study pen needles are included. The number of subjects with one or more events while using each PN is presented.

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.

Outcome measures

Outcome measures
Measure	4 mm / 8 mm PN n=173 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	4 mm / 5 mm PN n=89 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	8 mm PN n=84 Participants All randomized subjects that used the 8mm PN, either during the first or second 3 weeks of the study.
Number of Subjects With Severe Unexplained Hyperglycemic Events	0 participants	2 participants	1 participants

SECONDARY outcome

Timeframe: Visit 4: 18-24 days after starting 2nd pen needle

Population: Of the 167 subjects that completed the study, 137 subjects had within-window VAS pain scores for Visit 4 and were included in this analysis. Per the protocol, the allowable visit window was 18-24 days from Visit 3, when the subject switched from the 1st to 2nd assigned pen needle.

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.

Outcome measures

Outcome measures
Measure	4 mm / 8 mm PN n=69 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	4 mm / 5 mm PN n=68 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	8 mm PN All randomized subjects that used the 8mm PN, either during the first or second 3 weeks of the study.
Relative Injection Pain Score Assessed by Subject	-23.26 mm Standard Error 4.24	-11.91 mm Standard Error 5.61	—

OTHER_PRE_SPECIFIED outcome

Timeframe: each PN was used for 3 weeks

After each insulin injection with a study pen needle, subjects recorded in their study diary if they observed insulin leakage from the injection site. Subjects were not required to make a diary entry if there was no leakage.

Outcome measures

Outcome measures
Measure	4 mm / 8 mm PN n=164 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	4 mm / 5 mm PN n=83 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	8 mm PN n=81 Participants All randomized subjects that used the 8mm PN, either during the first or second 3 weeks of the study.
Percentage of Subjects With at Least One Leakage Event	44 percent of subjects	47 percent of subjects	56 percent of subjects

OTHER_PRE_SPECIFIED outcome

Timeframe: each PN was used for 3 weeks

Population: The number of participants shown is the number of subjects that reported at least one event of leakage (see previous data table). The number of reported leakage events is presented for each droplet size category. No data were collected if there was no leakage.

If insulin leakage from the injection site was observed, subjects rated the size of the leakage droplet based on a visual scale provided in their diaries. Scores of 1+, 2+, 3+, and 4+ correspond to droplet sizes of 1, 10, 20 and 50 ul, respectively. Droplets larger than those shown on the scale were scored as 5+. Subjects were not required to make a diary entry if there was no leakage.

Outcome measures

Outcome measures
Measure	4 mm / 8 mm PN n=72 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	4 mm / 5 mm PN n=39 Participants use of one PN for insulin injections for 3 weeks, followed by 3 weeks with the alternate PN	8 mm PN n=45 Participants All randomized subjects that used the 8mm PN, either during the first or second 3 weeks of the study.
Reported Injection Site Leakage Events, by Pen Needle Type and Droplet Size 1+, or 1 ul	372 number of events	289 number of events	200 number of events
Reported Injection Site Leakage Events, by Pen Needle Type and Droplet Size 2+, or 10 ul	221 number of events	120 number of events	126 number of events
Reported Injection Site Leakage Events, by Pen Needle Type and Droplet Size 3+, or 20 ul	44 number of events	50 number of events	25 number of events
Reported Injection Site Leakage Events, by Pen Needle Type and Droplet Size 4+, or 50 ul	12 number of events	20 number of events	5 number of events
Reported Injection Site Leakage Events, by Pen Needle Type and Droplet Size 5+, or > 50 ul	1 number of events	2 number of events	1 number of events

Adverse Events

8mm PN

Serious events: 2 serious events

Other events: 24 other events

Deaths: 0 deaths

5mm PN

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

4mm PN

Serious events: 4 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	8mm PN n=84 participants at risk All randomized subjects that used the 8 mm pen needle.	5mm PN n=89 participants at risk All randomized subjects that used the 5 mm pen needle.	4mm PN n=173 participants at risk All randomized subjects that used the 4mm pen needle.
Gastrointestinal disorders Dyspepsia	1.2% 1/84 • Number of events 1 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	0.00% 0/89 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	0.00% 0/173 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/84 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	0.00% 0/89 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	0.58% 1/173 • Number of events 1 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/84 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	0.00% 0/89 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	0.58% 1/173 • Number of events 1 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.
Metabolism and nutrition disorders Hypoglycemic seizure	0.00% 0/84 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	0.00% 0/89 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	0.58% 1/173 • Number of events 1 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.
Cardiac disorders Myocardial infarction	1.2% 1/84 • Number of events 1 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	0.00% 0/89 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	0.00% 0/173 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.
Blood and lymphatic system disorders Non-Hodgkins lymphoma	0.00% 0/84 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	0.00% 0/89 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	0.58% 1/173 • Number of events 1 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.

Other adverse events

Other adverse events
Measure	8mm PN n=84 participants at risk All randomized subjects that used the 8 mm pen needle.	5mm PN n=89 participants at risk All randomized subjects that used the 5 mm pen needle.	4mm PN n=173 participants at risk All randomized subjects that used the 4mm pen needle.
Metabolism and nutrition disorders hypoglycemia	26.2% 22/84 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	23.6% 21/89 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	20.8% 36/173 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.
Metabolism and nutrition disorders hyperglycemia	4.8% 4/84 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	7.9% 7/89 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	4.0% 7/173 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.
Injury, poisoning and procedural complications Pain at injection site	13.1% 11/84 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	12.4% 11/89 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.	15.6% 27/173 • upon enrollment to study completion Adverse events collection began once subjects were enrolled and continued throughout the 6 week randomized intervention period. The Investigator considered all Serious Adverse Events as unlikely to be related to, or not related to, the study devices or procedures.

Additional Information

Kenneth Kassler-Taub, MD

BD Medical, Medical Affairs

Phone: 201 847 6729

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60