Date: 1 December 2006 Trial ID: MS Version: 1.0 Clinical Trial Report Report Synopsis Page: 1 of 5

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1 Report Synopsis Page: 1 of 5 Synopsis Trial Registration ID-number NCT IND Number No IND number. NovoFine Autocover needle received 510(k) clearance on 30 March 2005 Title of Trial An Open-label, Multicenter, Prospective Cross-Over Study of Preference and Safety of NovoFine Autocover Needles compared to BD SafetyGlide Syringes in the Hospital Setting Investigators Six Investigators in the U.S. Trial Sites Six sites in the U.S. Publications None Trial Period FPFV: 21 July 2005; LPLV: 02 June 2006 Development Phase IV Objectives Primary Objective: To assess the preference of the NovoFine Autocover Needle compared to the BD SafetyGlide Syringe by nurses in the hospital setting. Secondary Objectives: To assess the safety of the NovoFine Autocover Needle compared to the BD SafetyGlide Syringe as to the incidence of accidental needlestick injury. To assess device preference of NovoFine Autocover Needle compared to the BD SafetyGlide Syringe as measured by the Sharps-Safety and Needlestick Prevention Questionnaires. Methodology This was a Phase IV, multicenter, prospective, open-label, randomized, two-period crossover, comparative study of 18 weeks duration (comprising a 2-week screening period and a 16-week treatment period). The trial population included nurses and hospitalized patients with diabetes. Nurses were the primary population of interest. Patients were included because the study design required that the trial devices be used to administer insulin subcutaneously to patients. At the start of the study, each hospital was randomized to a device sequence by Inc. The nurses administered insulin injections subcutaneously to the eligible patients whose prescribed insulin was compatible with the device assigned to the nurse. Patients prescribed insulin was not altered at any time during the study. Each participating nurse was asked to administer a minimum of 100 subcutaneous insulin injections over the 16 weeks of the study (50 injections per period per device). Nurses were instructed in proper handling of trial devices. Only nurses demonstrating device proficiency were allowed to participate in the study.

2 Report Synopsis Page: 2 of 5 Number of Subjects Planned and Analysed Planned: 100 Nurses, 10,000 injections. Each participating nurse was asked to administer a minimum of 100 insulin injections subcutaneously over the 16 weeks of the study. Actual Subject Population: NovoFine b BD Syringe BD Syringe c NovoFine Total Subjects a Enrolled/randomized Subjects who performed no injection 9 (20.9%) 3 (5.7%) 12 (12.5%) Subjects who performed 1 injection 34 (79.1%) 50 (94.3%) 84 (87.5%) Discontinued Other d 6 (14.0%) 11 (20.8%) 17 (17.7%) Completed Trial 28 (65.1%) 39 (73.6%) 67 (69.8%) a. Subject refers to nurse. b. NovoFine BD Syringe refers to the sequence where NovoFine Autocover Needle is in the first period and BD SafetyGlide Syringe is in the second period. c. BD Syringe NovoFine refers to the sequence where BD SafetyGlide Syringe is in the first period and NovoFine Autocover Needle is in the second period. d. Other includes: low number of patients consenting; nurse changed her job, went to another facility, or was not willing to continue the study; no qualified patients for nurse to inject; or the nurse was pregnant and discontinued the study when her baby was born. Diagnosis and Main Criteria for Inclusion Nurses: Registered nurse with competence in subcutaneous (SC) injections for at least 4 weeks prior to the start of the trial must demonstrate proficiency with the insulin delivery device (NovoFine Autocover Needle or BD SafetyGlide Syringe) prior to using the device in patients. Patients: Hospitalized patients, age 18 years, with type 1 or type 2 diabetes mellitus requiring treatment with insulin by subcutaneous injection. Test Product, Dose and Mode of Administration, Batch Number NovoFine Autocover Needles 30 G x 8 mm (Lot Number 05B11E). The patients received their prescribed insulin by subcutaneous injection with the NovoFine Autocover Needle. Duration of Treatment 18 weeks (comprising a 2-week screening period and a 16-week treatment period) Reference Therapy, Dose and Mode of Administration, Batch Number BD SafetyGlide Syringes 29 G x 1/2 inch (Lot Numbers: and ). The patients received their prescribed insulin by subcutaneous injection with the BD SafetyGlide Syringe. Criteria for Evaluation Efficacy Primary Efficacy Endpoint To assess the preference of the NovoFine Autocover Needle compared to BD SafetyGlide Syringe by nurses in the hospital setting using the Device Preference Questionnaire for NovoFine Autocover Needle and BD Safety Glide Syringe. Secondary Efficacy Endpoints There were no secondary efficacy endpoints for this study.

3 Report Synopsis Page: 3 of 5 Criteria for Evaluation Safety The frequency of adverse events (needlestick injuries) related to the NovoFine Autocover Needle compared to the BD SafetyGlide Syringe when handled by nurses. Nurses responses on the Clinical Technical Complaint that included any comments regarding the NovoFine Autocover Needle or BD SafetyGlide Syringe, or any malfunctions or suspected malfunctions of either device when used during the study. Device preference of the NovoFine Autocover Needle compared to the BD SafetyGlide Syringe as measured by the Sharps-Safety and Needlestick-Prevention Questionnaires. Statistical Methods Efficacy analysis was performed on Per-Protocol population. The answer to the primary question about nurse s preference was binary: 1 (the NovoFine Autocover needle) or 0 (the BD Safety Glide syringe). The P-value for testing whether NovoFine Autocover is preferred over BD Safety Glide Syringe was presented using the Fisher s exact testing. Unless otherwise specified, all analyses were performed at 5% significance level and the confidence interval was 95% confidence interval. The incidence of needlestick injuries was compared between NovoFine Autocover Needle and BD Safety Glide Syringe using a Poisson log-linear model. In the log-linear model, number of needlestick injuries served as response variable, device, period and sequence served as the explanatory variable. Sharps-Safety and Needlestick-Prevention Questionnaire was completed for each device by the nurse. For the analysis of questions in the Sharps-Safety and Needlestick-Prevention Device Assessment Questionnaire, the response for each question was dichotomized (scores 1, 2 vs. 4 and 5; score 3 was treated as neutral or was not included in the analysis), and logistic regression was performed. Demography of Trial Population In this study, no baseline characteristics and demographics were collected for either nurses or patients. Efficacy Results Among the participating nurses, 40% of the nurses preferred the NovoFine Autocover Needle versus 60% who preferred the BD SafetyGlide Syringe. The difference in device preference between the two devices was not statistically significant irrespective of the device sequence. The preference rate of the NovoFine Autocover was > 60% at 3 sites, Atlanta Medical Center [67%], Genesis Good Samaritan Hospital [60%], and the Southern Ohio Medical Center (64%). However, the other 3 sites showed a lower preference rate for NovoFine Autocover needle (Baylor Medical Center at Irving [27%], Mt. Carmel St. Ann's Hospital [25%], and Cleveland Clinic Foundation [17%]). The low preference by the nurses may be due to the bias for the BD SafetyGlide Syringe over the FlexPen NovoFine Autocover needle, since the vial/syringe method is the predominant form for administration of insulin in the United Sates and is used by majority of the hospital staff. The other possibility may be due to the fact that the nurses performed fewer injections using the Autocover Needle (mean: about 21 injections; median: 15 injections) than using the BD SafetyGlide Syringe (mean: about 26 injections; median: 22 injections). Safety Results No needlestick injuries were reported in this study; no nurses discontinued due to adverse events. Three Clinical Technical Complaints were reported with the use of a device for the nurses and the patients. One nurse reported that after injecting insulin she noticed the insulin was leaking. The event was not related to the use of NovoFine Autocover Needle. For one patient, the nurse reported 3 events of excessive bleeding at the injection site. The event was evaluated as possibly related to the study device NovoFine Autocover Needle. One patient died of cardiac arrest. The design of the study required that only those clinical technical complaints reported by the patients that were related to the device be considered an adverse event. The death of this patient was not related to the device, and was therefore not an adverse event as defined by criteria in the protocol. No treatment-emergent adverse events (TEAEs) were reported by nurses. Four (1.8%) patients reported a total of 7 TEAE: infusion site pain (3 patients, 4 events) and injection site haemorrhage (1 patient, 3 events) while using the NovoFine Autocover Needle. All the adverse events reported were mild in severity. No TEAEs were reported by patients when using the BD SafetyGlide Syringe.

4 Report Synopsis Page: 4 of 5 No serious adverse events (SAE) resulting with the use of a device were reported by nurses or patients when using the NovoFine Autocover Needle or the BD SafetyGlide Syringe. Preference of safety features of NovoFine Autocover Needle in preventing needlestick injuries was confirmed based on the nurses response: Question Number a Question Autocover Needle b n (%) SafetyGlide Syringe b n (%) Q1 The safety feature can be activated using a one-handed technique. 58 (86.6) 63 (88.7) Q2 Use of this product requires you to use the safety feature. 62 (92.5) 43 (62.3) Q3 This product requires less time to use than a standard syringe. 47 (69.1) 60 (87.0) Q4 The safety feature works well with my hand size. 55 (80.9) 65 (90.3) Q5 The device is easy to handle while wearing gloves. 63 (92.6) 63 (88.7) Q6 The device provides a better alternative to traditional recapping. 61 (89.7) 64 (92.8) Q7 There is a clear and unmistakable change (either audible or visible) that 62 (91.2) 67 (94.4) occurs when the safety feature is activated. Q8 The safety feature operates reliably. 64 (94.1) 68 (94.4) Q9 The exposed sharp is permanently blunted or covered after use and prior 67 (98.5) 61 (89.7) to disposal. Q10 The user does not need extensive training for correct operation. 63 (92.6) 67 (95.7) Q11 The design of the device suggests proper use. 62 (88.6) 59 (85.5) Q12 It is difficult to skip a crucial step when using the device. 55 (79.7) 48 (69.6) Q13 During use of the device the user s hands remain behind the needle until 68 ( 100) 59 (83.1) the injection is completed and the safety mechanism is locked. Q14 The device minimizes the risk of user exposure to blood. 67 (97.1) 56 (78.9) Q15 The device minimizes the risk of infection (e.g. through crosscontamination). 66 (95.7) 59 (84.3) Q16 The device is easy to dispose of after use. 66 (95.7) 64 (91.4) Q17 The safety feature of the device helps to reduce my anxiety about 62 (91.2) 62 (86.1) accidental needlesticks. Q18 Overall, I would recommend using the device (possible to recommend both). 47 (69.1) 62 (86.1) a. Answer scores of Q1-Q18: On a 5-point scale, 1and 2 = agree, 3=neither agree or disagree, 4 and 5 = disagree b. The responses to the questions indicate agree (rating 1 and 2) Characteristics favorable to the use of the NovoFine Autocover needle included: Question 2: the requirement to use the safety device, Question 9 the permanent blunting or covering of the needle after use and prior to disposal, Question 14: the minimized risk of exposure to blood, and Question 15: the minimized risk of infection through cross-contamination from a needlestick. Characteristics favorable to the use of the SafetyGlide needle included: Question 3 the requirement of less time to use than a standard syringe and Question 18: greater recommendation of the SafetyGlide needle (86%) versus the Autocover (69%). All the nurses agreed that, during the use of the NovoFine Autocover Needle, the user s hands remained behind the needle until the injection was completed and the safety mechanism was locked. More nurses responded that they experienced some difficulty associated with the use of the NovoFine Autocover Needle versus the BD SafetyGlide Syringe. Difficulties experienced in the use of the NovoFine Autocover Needle included: it was difficult to determine whether the patient actually received the insulin dose indicated since you cannot visualize if the needle penetrated the patient s skin because of the safety device; it appeared that one had to apply more

5 Report Synopsis Page: 5 of 5 pressure for the needle to enter the patient's skin; with some skin types it was difficult to fully engage Autocover after the injection; and medicine was noted on skin after injection. Difficulties experienced in the use of the BD-SafetyGlide Syringe included: safety feature of the SafetyGlide syringe was not automatic; difficulty reading smaller units of syringe due to safety device in the way; and syringe can be awkward at times. Conclusions No needlestick injuries were reported in this study indicating that the NovoFine Autocover Needle was as safe as the BD-SafetyGlide Syringe. No significant difference in preference to either safety device was reported by the participating nurses, irrespective of the device sequence. In general, the nurses responded favorably for the handling and acceptance of both the devices. Sixty-nine percent of the nurses said they would recommend the use of the NovoFine Autocover Safety needle and gave many advantageous benefits to the Autocover needle in preventing needlestick injuries. The trial was conducted in accordance with the Declaration of Helsinki and ICH Good Clinical Practice.