NCT04414579

The Efficacy and Safety of Faster Insulin Aspart (Fiasp®) Compared to Conventional Insulin Aspart (NovoLog®) as Correction Bolus

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

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: Mountain Diabetes and Endocrine Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• Type 1 Diabetes Mellitus

Interventions

Type	Name	Description
DRUG	Faster Insulin Aspart (Fiasp®)	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.

Timeline

• Start date: 2019-03-27
• Primary completion: 2021-03-01
• Completion: 2021-03-01
• First posted: 2020-06-04
• Last updated: 2020-11-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study