- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04414579
The Efficacy and Safety of Faster Insulin Aspart (Fiasp®) Compared to Conventional Insulin Aspart (NovoLog®) as Correction Bolus (PLATEAU)
The Efficacy and Safety of Faster Insulin Aspart (Fiasp®) Compared to Conventional Insulin Aspart (NovoLog®) as Correction Bolus in Patients With Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion (CSII) and Continuous Glucose Monitoring (CGM): a Cross-over Controlled Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Patients with type 1 DM using CSII require bolus insulin for two purposes: first, to cover carbohydrate intake to control postprandial glucose, and second, to correct episodes of hyperglycemia. The latter function is referred to as a "correction dose" or "correction bolus". Insulin pumps have bolus calculators which calculate correction doses based on the patient's individualized BG target and insulin sensitivity factor (ISF). Rapid-acting insulin analogues delivered by pump typically require 2 to 4 hours to fully correct an acute hyperglycemic episode, and sometimes multiple correction doses are needed to normalize the blood glucose level. This can be frustrating for patients, particularly when a correction bolus is necessary in addition to a meal bolus; frequently, patients must wait for the correction bolus to take effect and delay eating until the blood glucose has begun to normalize to avoid severe postprandial hyperglycemia. There is consequently an unmet need in insulin delivery, and in particular in CSII, for an insulin which can correct a hyperglycemic episode more rapidly than is currently possible with rapid-acting insulin analogues.
Faster insulin aspart (Fiasp) is a novel formulation of insulin aspart with an accelerated time-action profile which results in twice the exposure to insulin and 74% greater insulin action within the first 30 minutes after injection compared to conventional insulin aspart. This results in twice-as-fast onset of appearance in the bloodstream (4 vs. 9 min compared to conventional insulin aspart) which has been demonstrated to reduce postprandial glucose levels in patients with type 1 DM using CSII. Theoretically, this faster insulin action would be useful in correction dosing during acute episodes of hyperglycemia to normalize the blood glucose level more rapidly than is currently possible with conventional insulin aspart (NovoLog).
Many patients with type 1 DM using CSII now also use continuous glucose monitoring (CGM) for making insulin dosing decisions. Currently the FDA has approved 2 CGM systems for nonadjunctive use in bolus insulin dose calculations. Only one of these systems, the Dexcom, reads continuously to the patient and has alarms to warn of impending episodes of hyper- or hypoglycemia, and this is the system used most commonly by patients with type 1 DM using open-loop CSII. Patients now incorporate the Dexcom trend arrow, which depicts the rate and direction of glucose change, into the correction dose calculation, and recommendations on how to incorporate CGM information into correction dose calculations have recently been updated based on an expert consensus report. However, these guidelines were created for use with rapid acting insulin analogues. How they might need to be modified for use with Fiasp (the first and only ultra-rapid insulin analogue) is not known.
The purpose of this investigator-initiated trial is to compare the efficacy in terms of time to recovery from hyperglycemia as measured by time to arrest of hyperglycemic excursion ("glucose plateau point", primary endpoint) and return to premeal glucose target if feasible (secondary endpoint) between Fiasp and conventional insulin aspart when used as a correction bolus. These endpoints will be determined by CGM (Dexcom) from data exported from the Dexcom Clarity program.
Study hypothesis:
Compared to conventional insulin aspart, Fiasp will correct hyperglycemia (defined as arrest of rise of blood glucose, following correction bolus, ie, GPP ) faster than conventional insulin aspart in subjects with type 1 DM using CSII.
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Wendy S Lane, MD
- Phone Number: 8286849588
- Email: mountaindiabetes@msn.com
Study Contact Backup
- Name: Melinda L Buford, RN, BSN
- Phone Number: 314 8286849588
- Email: mbuford@mdecresearch.com
Study Locations
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North Carolina
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Asheville, North Carolina, United States, 28803
- Recruiting
- Mountain Diabetes and Endocrine Center
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Contact:
- Melinda L Buford, RN, BSN
- Phone Number: 314 828-684-9588
- Email: mbuford@mdecresearch.com
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Sub-Investigator:
- Stephen L Weinrib, MD
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Sub-Investigator:
- Lynn L Baru, MD
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Sub-Investigator:
- Michael D Skrzynski, ANP
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male and female patients > 18 years of age
- Type 1 DM of > 1 year duration
- Use of any open loop insulin pump, Tandem T-Slim with Basal IQ, Insulet Omnipod Dash, or any other investigator-approved insulin pumps with Dexcom CGM G5, G6, or newer version for > 6 months
- Good baseline glycemic control (HbA1c < 7.5%; low risk of hypoglycemia by CGM as defined by Dexcom Clarity report)
- No episodes of severe hypoglycemia in the previous 3 months
- Pump download shows regular meal bolusing, accurate carbohydrate counting ability, and willingness to use exercise markers in Dexcom
- CGM download shows regular use (>85% of time) and regular calibration if using G5 sensor (G6 requires no calibration)
- Females using adequate contraception
Exclusion Criteria:
- Use of CGM other than Dexcom G5 or G6 or a newer Dexcom CGM version
- Suboptimal baseline glycemic control (HbA1c > 7.5%)
- Pump or CGM download shows suboptimal use of devices (lack of meal boluses, frequent overrides of pump, excessive pump suspension, inadequate calibration or inconsistent usage of CGM)
- Serious comorbidities including CVD with recent event, actively treated malignancy, renal dysfunction with eGFR < 45 ml/min, or any other condition which in the opinion of the investigator would preclude subject's ability to participate in trial
- Females unwilling to use contraception, planning pregnancy or breastfeeding
- Use of any other glucose-lowering agents than insulin
- Hypersensitivity to insulin aspart or one of the excipients in faster insulin aspart
- Known diabetic gastroparesis
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
No Intervention: No Intervention: Conventional Insulin Aspart (NovoLog®)
In the aspart group, the subject will only take aspart through the their pump.
This study population will have an established expertise in diabetes self-management with previous knowledge of insulin pump therapy and Dexcom Continuous Glucose Monitoring (CGM).
Allowing the subjects to use their insulin pumps for bolus insulin delivery, as they are accustomed, will minimize the chances of skipping meal boluses and correction doses.
Aspart is put into their pump and delivered to their body through a small tube placed under your skin.
In this NovoLog®-only treatment group, the subject will take aspart with each meal while your pump also gives you a slow, continuous dose of aspart for basal insulin.
This treatment group is very similar (or even identical) to the treatment the subject was receiving prior to starting the study.
|
|
Active Comparator: Faster Insulin Aspart (Fiasp®)
In the Fiasp group, the subject will only take aspart through the their pump.
This study population will have an established expertise in diabetes self-management with previous knowledge of insulin pump therapy and Dexcom Continuous Glucose Monitoring (CGM).
Allowing the subjects to use their insulin pumps for bolus insulin delivery, as they are accustomed, will minimize the chances of skipping meal boluses and correction doses.
Fiasp is put into their pump and delivered to their body through a small tube placed under their skin.
In this Fiasp treatment group, the subject will take fiasp with each meal while their pump also gives them a slow, continuous dose of aspart for basal insulin.
This treatment group is very similar (or even identical) to the treatment the subject was receiving prior to starting the study.
|
Subjects will be randomized either to use Fiasp or conventional insulin aspart in CSII.
CSII settings (basal, bolus, and correction factors) will be optimized using a meal challenge for a 2-week run in period followed by a 10-week period of CSII use with the assigned insulin.
After a 12-week maintenance period, each group will cross over to the other insulin (conventional insulin aspart or Fiasp) by CSII for a second 2-week optimization period followed by a 10-week treatment period.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to stabilization of rising blood sugar by CGM after correction bolus
Time Frame: 2 weeks
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Time (in minutes) to stabilization of rising blood sugar (GPP) by CGM after correction bolus during the final 2 week maintenance period.
Two categories of correction dose will be analyzed: 1) those following an isolated correction dose (taken independently of a meal dose), and 2) those taken as part of a combination bolus with a meal dose.
|
2 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of early hypoglycemia
Time Frame: 25 weeks
|
Incidence of early hypoglycemia (Blood glucose < 54 mg/dl within 1 and 2 hours) following correction bolus with each insulin (Key Safety Endpoint)
|
25 weeks
|
Change in Insulin Sensitivity Factor
Time Frame: 25 weeks
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Change in Insulin Sensitivity Factor, if any, required for hypoglycemia prevention using Fiasp as recorded by continuous subcutaneous insulin infusion device setting report
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25 weeks
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Change in Insulin On Board
Time Frame: 25 weeks
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Change in Insulin On Board, if any, required for prevention of late hyperglycemia using Fiasp as recorded by continuous subcutaneous insulin infusion device setting report
|
25 weeks
|
GlycoMark differences between arms
Time Frame: 25 weeks
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GlycoMark (1,5 anhydroglucitol, a marker of postprandial glucose excursion) during use of each insulin.
|
25 weeks
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HbA1c differences between arms
Time Frame: 25 weeks
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HbA1c during use of each insulin
|
25 weeks
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Percent time spent in target range, hyperglycemic range, and hypoglycemic range
Time Frame: 4 weeks
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Percent time spent in target range, hyperglycemic range and hypoglycemic range by Continuous Glucose Monitoring (CGM) on each insulin during the final 2 weeks of each treatment period.
Target ranges include 70-180 mg/dL.
Hyperglycemia ranges to be captured will include Category 1: 181-250 mg/dL and Category 2: above 250 mg/dL.
Hypoglycemia ranges to be captured include Category 1: 69-54 mg/dL and Category 2: below 54 mg/dL.
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4 weeks
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Standard deviation differences between arms
Time Frame: 4 weeks
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Standard deviation of mean blood glucose as determined by CGM on each insulin
|
4 weeks
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Treatment related impact measures between arms
Time Frame: 6 weeks
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Treatment related impact measures on each insulin using TRIM D questionnaire
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6 weeks
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Collaborators and Investigators
Publications and helpful links
General Publications
- Bergenstal RM, Garg S, Weinzimer SA, Buckingham BA, Bode BW, Tamborlane WV, Kaufman FR. Safety of a Hybrid Closed-Loop Insulin Delivery System in Patients With Type 1 Diabetes. JAMA. 2016 Oct 4;316(13):1407-1408. doi: 10.1001/jama.2016.11708. No abstract available.
- Bode BW, Johnson JA, Hyveled L, Tamer SC, Demissie M. Improved Postprandial Glycemic Control with Faster-Acting Insulin Aspart in Patients with Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion. Diabetes Technol Ther. 2017 Jan;19(1):25-33. doi: 10.1089/dia.2016.0350. Epub 2017 Jan 5.
- Aleppo G, Laffel LM, Ahmann AJ, Hirsch IB, Kruger DF, Peters A, Weinstock RS, Harris DR. A Practical Approach to Using Trend Arrows on the Dexcom G5 CGM System for the Management of Adults With Diabetes. J Endocr Soc. 2017 Nov 20;1(12):1445-1460. doi: 10.1210/js.2017-00388. eCollection 2017 Dec 1.
- Heise T, Pieber TR, Danne T, Erichsen L, Haahr H. A Pooled Analysis of Clinical Pharmacology Trials Investigating the Pharmacokinetic and Pharmacodynamic Characteristics of Fast-Acting Insulin Aspart in Adults with Type 1 Diabetes. Clin Pharmacokinet. 2017 May;56(5):551-559. doi: 10.1007/s40262-017-0514-8.
- Russell-Jones D, Bode BW, De Block C, Franek E, Heller SR, Mathieu C, Philis-Tsimikas A, Rose L, Woo VC, Osterskov AB, Graungaard T, Bergenstal RM. Fast-Acting Insulin Aspart Improves Glycemic Control in Basal-Bolus Treatment for Type 1 Diabetes: Results of a 26-Week Multicenter, Active-Controlled, Treat-to-Target, Randomized, Parallel-Group Trial (onset 1). Diabetes Care. 2017 Jul;40(7):943-950. doi: 10.2337/dc16-1771. Epub 2017 Mar 29.
- Klonoff DC, Evans ML, Lane W, Kempe HP, Renard E, DeVries JH, Graungaard T, Hyseni A, Gondolf T, Battelino T. A randomized, multicentre trial evaluating the efficacy and safety of fast-acting insulin aspart in continuous subcutaneous insulin infusion in adults with type 1 diabetes (onset 5). Diabetes Obes Metab. 2019 Apr;21(4):961-967. doi: 10.1111/dom.13610. Epub 2019 Jan 13.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Immune System Diseases
- Autoimmune Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 1
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Insulin
- Insulin, Globin Zinc
- Insulin Aspart
- Insulin, Long-Acting
- Insulin degludec, insulin aspart drug combination
Other Study ID Numbers
- GPP2019
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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