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| General |
| Study Status |
Ongoing |
Application Number /
Requirement Number |
P160017 S031/ PAS001 |
| Date Original Protocol Accepted |
06/21/2018
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| Date Current Protocol Accepted |
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| Study Name |
Post-Approval Study
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| Device Name |
MiniMed 670G System
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| General Study Protocol Parameters |
| Study Design |
Randomized Clinical Trial
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| Data Source |
New Data Collection
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| Comparison Group |
Concurrent & Historical Control
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| Analysis Type |
Descriptive
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| Study Population |
Child: 2-12 yrs,
Adolescent: 13-18 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
This is a multi-center, randomized, parallel, adaptive controlled trial in adult and pediatric patients with Type 1 Diabetes using Hybrid Closed Loop System (HCL) and/or control (CSII, MDI, or SAP) in the home setting. Three cohorts, each consisting of a control arm (CSII, MDI, or SAP) and an HCL arm and further divided by A1C group (A1C > 8% or A1C < 8%), will participate in the 6-month study period followed by a 6-month continuation period where all subjects will use HCL. The purpose of this study is to demonstrate the safety and effectiveness of the HCL in the study population. The device is investigational in subjects ages 2-6 years and non-investigational in subjects 7 years and up.
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| Study Population |
Adult and pediatric patients (2-80 years of age) with type 1 diabetes that meet the inclusion/exclusion criteria will be studied.
The device is investigational in ages 2-6 years. The 2-6 year age group is also being studied under an approved IDE.
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| Sample Size |
A minimum of 1120 subjects will be enrolled.
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| Key Study Endpoints |
Primary Safety Endpoint
The primary safety endpoint is the event rate of severe hypoglycemia and DKA from both A1C Groups (baseline A1C > 8% and baseline A1C < 8%) during the first 6 months of study phase and second 6 months of continuation phase. The descriptive summary statistics will be presented by number of event and event rate (100 patient years) for severe hypoglycemia and DKA separately.
The safety of the study will be evaluated and summarized per arm, including but not limited to the following:
• Diabetic ketoacidosis (DKA)
• Severe hypoglycemia
• Severe hyperglycemia
• Serious adverse events (SAEs)
• Unanticipated adverse device effects (UADEs)
Descriptive analyses will be performed to assess the primary safety endpoint. Event rates of severe hypoglycemia and DKA will be compared to: (1) the target event rate (defined by the medical literature and other studies) and (2) the control groups (CSII, MDI, SAP).
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| Follow-up Visits and Length of Follow-up |
Follow-up visits are scheduled throughout the study period up to 6 months and throughout the continuation period up to 6 months.
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
142 (eighteen 2-6 years old and one hundred twenty-four 7-13 years old)
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| Actual Number of Sites Enrolled |
9 for the 2-6 years old cohort and 20 for the 7-13 years old cohort
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| Patient Follow-up Rate |
A total of 142 subjects ages 2 - 13 years (eighteen 2-6 years old and one hundred twenty-four 7-13 years old) were enrolled across all three treatment cohorts of the study. The Sponsor had an overall minimum enrollment goal of 1,120 subjects for all age groups (participants 2 years and older). Results are summarized by treatment cohort below.
Cohort 1 (Hybrid Closed Loop (HCL) vs Continuous Subcutaneous Insulin Infusion (CSII)): A total of 32 subjects (one 2-6 years old and thirty-one 7-13 years old) were enrolled in the study. A total of 28 subjects (one 2-6 years old and twenty-seven 7-13 years old) entered the Study Period. A total of 27 subjects (one 2-6 years old and twenty-six 7-13 years old) completed the Study Period. The follow-up rate was 96.4% (27/28).
Cohort 2 (HCL vs Multiple Daily Injection (MDI)): A total of 39 subjects (eight 2-6 years old and thirty-one 7-13 years old) were enrolled in the study. A total of 39 subjects (eight 2-6 years old and thirty-one 7-13 years old) entered the Study period. A total of 37 subjects (seven 2-6 years old and thirty 7-13 years old) completed the Study period. The follow-up rate was 94.9% (37/39).
Cohort 3 (HCL vs Sensor Augmented Pump (SAP)): A total of 71 subjects (nine 2-6 years old and sixty 7-13 years old) were enrolled in the study. A total of 61 subjects (nine 2-6 years old and fifty-two 7-13 years old) entered the Study period. A total of 50 subjects (seven 2-6 years old and forty-three 7-13 years old) completed the Study period. The follow-up rate was 82.0% (50/61).
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| Final Safety Findings |
2-6 Years Old:
Cohort 1: Of the 1 adverse events reported through the end of the Study Period, 100% (N=1) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia), and bleeding at the sensor insertion site. There were no reports of DKA, no reports of severe hypoglycemia, and no reports of severe hyperglycemia.
Cohort 2: Of the 31 adverse events reported through the end of the Study period, 23% (N=7) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia), skin issues (e.g., dermatitis, skin irritation), and bleeding at the sensor insertion site. There were no reports of DKA, no report of severe hypoglycemia, and 3 reports of severe hyperglycemia.
Cohort 3: Of the 12 adverse events reported through the end of the Study period, 17% (N=2) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia) and skin issues (e.g., dermatitis and/or skin irritation at the sensor site, skin infection at the infusion set site). There were no reports of DKA, no reports of severe hypoglycemia, and 2 reports of severe hyperglycemia.
There were no reports of serious unanticipated adverse device effects or deaths.
7-13 Years Old:
Cohort 1: Of the 76 adverse events reported through the end of the Study Period, 12% (N=9) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia), and bleeding at the sensor insertion site. There were no reports of DKA, no reports of severe hypoglycemia, and 23 reports of severe hyperglycemia.
Cohort 2: Of the 78 adverse events reported through the end of the Study period, 19% (N=15) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia), skin issues (e.g., dermatitis, skin irritation), and bleeding at the sensor insertion site. There were no reports of DKA, 1 report of severe hypoglycemia, and 5 reports of severe hyperglycemia.
Cohort 3: Of the 152 adverse events reported through the end of the Study period, 30% (N=45) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia) and skin issues (e.g., dermatitis and/or skin irritation at the sensor site, skin infection at the infusion set site). There were 3 reports of DKA, no reports of severe hypoglycemia, and 30 reports of severe hyperglycemia.
There were no reports of serious unanticipated adverse device effects or deaths.
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| Final Effect Findings |
The co-primary effectiveness endpoints for all three cohorts were stratified into two groups: Group 1 for subjects with a baseline A1C > 8%, and Group 2 for subjects with a baseline A1C = 8%.
Ages 2-6:
Cohort 1:
Group 1 (baseline A1C >8%): change in A1C:
There was no subject 2-6 years of age in Group 1 with baseline A1C > 8% enrolled in the CSII Cohort.
Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range:
There was 1 subject 2-6 years of age in Group 2 with baseline A1C = 8% enrolled in the CSII Cohort. This subject did not have 3-month or 6-month time-in-hypoglycemic-range (%) measurements.
Cohort 2:
Group 1 (baseline A1C >8%): change in A1C:
From baseline to end of study, the mean change in A1C was -0.8±1.0% (95% Confidence Interval (CI): -2.1, 0.5) for the HCL Arm (N=5). There were no subjects in the Control Arm.
Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range:
From baseline to end of study, the mean change in time in hypoglycemic range was 2.6±0.5% (95% Confidence Interval (CI): -1.5, 6.7) for the HCL Arm (N=2). There were no subjects in the Control Arm.
Cohort 3:
Group 1(baseline A1C >8%): change in A1C:
From baseline to end of study, the change in A1C was 0.6 for the HCL Arm (N=1) and 0.1 for the Control Arm (N=1). The difference (HCL vs SAP) was 0.5.
Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range:
From baseline to end of study, the mean change in time in hypoglycemic range was 5.0±3.2% (95% Confidence Interval (CI): -0.2, 10.1) for the HCL Arm (N=4). There were no subjects in the Control Arm.
Ages 7-13:
Cohort 1:
Group 1 (baseline A1C >8%): change in A1C:
From baseline to end of study, the mean change in A1C was -1.1±0.5% (95% Confidence Interval (CI): -1.4, -0.7) for the HCL Arm (N=10) and -0.1±1.1% (95% CI: -1.0, 0.7) for the Control Arm (N=9). The estimated mean difference (HCL vs CSII) was -0.9±0.9% (95% CI: -1.7, -0.1).
Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range:
From baseline to end of study, the mean change in time in hypoglycemic range was 3.3±1.0% (95% Confidence Interval (CI): 1.8, 4.9) for the HCL Arm (N=4) and 2.8±2.2% (95% CI: -2.7, 8.4) for the Control Arm (N=3). The estimated mean difference (HCL vs CSII) was 0.5±1.6% (95% CI: -2.7,3.7).
Cohort 2:
Group 1 (baseline A1C >8%): change in A1C:
From baseline to end of study, the mean change in A1C was -0.9±1.0% (95% Confidence Interval (CI): -2.0, 0.1) for the HCL Arm (N=6) and -0.4±0.7% (95% CI: -0.9, 0.2) for the Control Arm (N=8). The estimated mean difference (HCL vs MDI) was -0.5±0.8% (95% CI: -1.5,0.4).
Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range:
From baseline to end of study, the mean change in time in hypoglycemic range was 2.8±2.6% (95% Confidence Interval (CI): 1.0, 4.7) for the HCL Arm (N=10) and 13.2±12.1% (95% CI: -6.0, 32.5) for the Control Arm (N=4). The estimated mean difference (HCL vs MDI) was -10.4±6.4% (95% CI: -18.7, -2.1).
Cohort 3:
Group 1 (baseline A1C >8%): change in A1C:
From baseline to end of study, the mean change in A1C was -0.4±0.9% (95% Confidence Interval (CI): -0.9, 0.1) for the HCL Arm (N=14) and 0.3±1.3% (95% CI: -0.8, 1.3) for the Control Arm (N=9). The estimated mean difference (HCL vs SAP) was -0.7±1.1% (95% CI: -1.6,0.2).
Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range:
From baseline to end of study, the mean change in time in hypoglycemic range was 3.1±1.6% (95% Confidence Interval (CI): 1.7, 4.5) for the HCL Arm (N=8) and 4.1±2.8% (95% CI: 2.3, 5.8) for the Control Arm (N=12). The estimated mean difference (HCL vs SAP) was -1.0±2.4% (95% CI: -3.3,1.3).
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| Study Strengths & Weaknesses |
Strengths: This post-approval study included users aged 2-13 across 29 sites transitioning to the MiniMed 670G/770G Hybrid Closed Loop system from three different baseline therapy options (MDI, CSII and SAP). The incident rates of safety events (severe hypoglycemia and diabetic ketoacidosis) of users on the MiniMed 670G/770G were below the prespecified threshold for all cohorts. The post-approval study confirms that the MiniMed 670G/770G System is safe when used as intended.
Weaknesses: The study did not reach its enrollment goals for pediatric users 2-6 and 7-13 years old despite multiple efforts from the sponsor to increase enrollment. However, available data from this post-approval study and additional data from the post-market surveillance program support safety of the MiniMed 670G/770G System when used as intended in these age groups.
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| Recommendations for Labeling Changes |
Results of the post-approval study does not change the benefits and risks conclusions of the original PMA approval. Labeling changes are recommended to include PAS results.
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