CONtinuous Subcutaneous Insulin Infusion STudy ENrolling Type 1 (CONSISTENT 1): Evaluation of Metabolic Outcomes and Safety of Hylenex Recombinant (Hyaluronidase Human Injection) Used as a Preadministration Infusion Site Treatment in Subjects With Type 1 Diabetes (T1DM) Using Continuous Subcutaneous Insulin Infusion (CSII)
Overview
- Phase
- Phase 4
- Intervention
- Commercial Hylenex® recombinant (hyaluronidase human injection)
- Conditions
- Type 1 Diabetes Mellitus
- Sponsor
- Halozyme Therapeutics
- Enrollment
- 456
- Locations
- 1
- Primary Endpoint
- Change From Baseline to 6 Months in Glycosylated Hemoglobin (HbA1c)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The primary objectives of this study are to compare the difference in glycosylated hemoglobin (HbA1c) from baseline to Month 6 using Hylenex recombinant preadministration in continuous subcutaneous insulin infusion (CSII) versus standard CSII and to evaluate the safety of Hylenex recombinant preadministration, including local tolerability, adverse events, and hypo- and hyperglycemia rates.
Detailed Description
This Phase 4 study is designed to demonstrate noninferiority of pretreatment with Hylenex recombinant in the CSII setting to rapid-acting analog insulin alone with respect to glycemic control as assessed by changes in HbA1c in participants with Type 1 diabetes mellitus. Total duration of study treatment is 24 months. However, according to the study design, the primary outcome measure is to be assessed at 6 months and an interim analysis is to be completed at 6 months for the secondary outcome measures and adverse events. Therefore, data reported in this clinical trials record is for the 6-month interim analysis.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female of age 18 years or older with a history of T1DM for at least 12 months
- •Glycosylated hemoglobin (HbA1c) 6.5% to 9.5% (inclusive) based on central laboratory results
- •Fasting C-peptide \<0.6 nanograms per milliliter (ng/mL)
- •Current use of an insulin pump compatible with available tubing for Hylenex recombinant infusion and use of an infusion set compatible with the tubing available or willingness to switch to an infusion set compatible with tubing available for infusion of Hylenex recombinant
- •Current treatment at the time of screening with insulin \<300 units per day (U/day)
- •Participants who routinely use continuous glucose monitoring (CGM) (defined as average CGM use 5 or more days per week over the preceding 3 months) and those who do not routinely used CGM are both eligible for inclusion in the study. Intermittent use of CGM is also acceptable but will not be a criterion use for stratified randomization.
- •Participants should be in good general health based on medical history and physical examination, without medical conditions that might prevent the completion of study drug infusions and assessments required in this protocol.
Exclusion Criteria
- •Type 2 diabetes
- •Known or suspected allergy to any component of any of the study drugs in this study
- •Severe proliferative retinopathy or maculopathy, and/or gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, of such severity as to impede the participant's ability to comply with protocol procedures, as judged by the Investigator
- •History of transmural myocardial infarction, congestive heart failure and uncontrolled hypertension (diastolic blood pressure \[BP\] consistently \>100 millimeters of mercury \[mmHg\]) are exclusionary
- •As judged by the Investigator, clinically significant active disease of the gastrointestinal, cardiovascular (including history of stroke, history of arrhythmia, or conduction delays on electrocardiogram \[ECG\]), hepatic, neurological, renal, genitourinary, pulmonary, or hematological systems of such severity as to impede the participant's ability to comply with protocol procedures
- •History of any illness or disease that in the opinion of the Investigator might confound the results of the study or pose additional risk in administering the study drugs to the participant
- •As judged by the Investigator, clinically significant findings in routine laboratory data at screening
- •Use of drugs that may interfere with the interpretation of study results or are known to cause clinically relevant interference with hyaluronidase action, insulin action, glucose utilization, or recovery from hypoglycemia (including systemic pharmacologic corticosteroid). Use of pramlintide or a glucagon-like peptide \[GLP\]-1 receptor agonist is not exclusionary but participants using these agents will be subjected to stratified randomization. Use of aspirin (acetylsalicylic acid \[ASA\]) up to 325 milligrams (mg)/day is not exclusionary but should be noted for analysis.
- •Hypoglycemic unawareness of such severity as to impede the participant's ability to comply with protocol procedures, as judged by the Investigator.
- •Current addiction to alcohol or substance abuse as determined by the Investigator.
Arms & Interventions
Commercial Hylenex Recombinant (Formulation 1)
Hylenex Formulation 1: For 6 months, participants received their regular treatment of rapid-acting continuous subcutaneous insulin infusion (CSII) (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of the commercial form of Hylenex recombinant, delivered at 150 units (U) through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
Intervention: Commercial Hylenex® recombinant (hyaluronidase human injection)
Commercial Hylenex Recombinant (Formulation 1)
Hylenex Formulation 1: For 6 months, participants received their regular treatment of rapid-acting continuous subcutaneous insulin infusion (CSII) (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of the commercial form of Hylenex recombinant, delivered at 150 units (U) through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
Intervention: Insulin lispro
Commercial Hylenex Recombinant (Formulation 1)
Hylenex Formulation 1: For 6 months, participants received their regular treatment of rapid-acting continuous subcutaneous insulin infusion (CSII) (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of the commercial form of Hylenex recombinant, delivered at 150 units (U) through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
Intervention: Insulin aspart
Commercial Hylenex Recombinant (Formulation 1)
Hylenex Formulation 1: For 6 months, participants received their regular treatment of rapid-acting continuous subcutaneous insulin infusion (CSII) (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of the commercial form of Hylenex recombinant, delivered at 150 units (U) through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
Intervention: Insulin glulisine
Precommercial Hylenex Recombinant (Formulation 2)
Hylenex Formulation 2: For 6 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of the precommercial form of Hylenex recombinant, delivered at 150 units (U) through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
Intervention: Precommercial Hylenex recombinant (hyaluronidase human injection)
Precommercial Hylenex Recombinant (Formulation 2)
Hylenex Formulation 2: For 6 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of the precommercial form of Hylenex recombinant, delivered at 150 units (U) through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
Intervention: Insulin lispro
Precommercial Hylenex Recombinant (Formulation 2)
Hylenex Formulation 2: For 6 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of the precommercial form of Hylenex recombinant, delivered at 150 units (U) through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
Intervention: Insulin aspart
Precommercial Hylenex Recombinant (Formulation 2)
Hylenex Formulation 2: For 6 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of the precommercial form of Hylenex recombinant, delivered at 150 units (U) through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
Intervention: Insulin glulisine
Standard Rapid-Acting Insulin CSII
Participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Intervention: Insulin lispro
Standard Rapid-Acting Insulin CSII
Participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Intervention: Insulin aspart
Standard Rapid-Acting Insulin CSII
Participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Intervention: Insulin glulisine
Outcomes
Primary Outcomes
Change From Baseline to 6 Months in Glycosylated Hemoglobin (HbA1c)
Time Frame: Baseline; 6 Months
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline to 12 Months in HbA1c
Time Frame: Baseline; 12 Months
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Secondary Outcomes
- Number of Participants Achieving HbA1c <7.0% and HbA1c ≤6.5% at Month 12(Month 12)
- Mean Glucose Excursions at 6 Months(After Month 1 up to Month 6)
- Change From Baseline in Body Weight to Month 12(Baseline; Week 2; Months 1, 2, 3, 4, 6, 9, and 12)
- Rates of Hypoglycemia Events (HE) to Month 6(After Month 1 up to Month 6)
- Standard Deviation of Self-Monitoring Blood Glucose Values at 6 Months(After Month 1 up to Month 6)
- Rates of HEs to Month 12(After Month 1 up to Month 12)
- Rates of Hyperglycemia Events to Month 6(After Month 1 up to Month 6)
- Change From Baseline in Average Weighted Impact ADDQoL Values at Month 12(Baseline; Month 12)
- Time Per Day <56 Milligrams Per Deciliter (mg/dL), ≤70 mg/dL, >70 mg/dL, <140 mg/dL, ≥140 mg/dL, Outside of 71 to 180 mg/dL, and Outside of 71 to 139 mg/dL(Randomization to Month 12)
- Average of Daily Insulin Doses (Bolus, Basal, and Total)(from Randomization up to Month 12)
- Average Carbohydrate Factor (CarbF) Values(Month 1 to Month 12)
- Average of Bolus Times Relative to Meal Times(Month 1 to Month 12)
- Number of Participants With the Indicated Responses to the Device Handling Questions(Month 12)
- Rates of Hyperglycemia Events to Month 12(After Month 1 up to Month 12)
- Mean Glucose Excursions at 12 Months(After Month 1 up to Month 12)
- Standard Deviation of Self-Monitoring Blood Glucose Values at 12 Months(After Month 1 up to Month 12)
- Area Per Day <56 mg/dL, ≤70 mg/dL, ≥140 mg/dL, Outside of 71 to 180 mg/dL, and Outside of 71 to 139 mg/dL(Randomization to Month 12)
- Mean Additional Time for Hylenex Pre-administration(Month 12)
- Average Correction Factor (CorrF) Values(Month 1 to Month 12)
- Average Glucose, Median Glucose, and Average Daily Standard Deviation(Randomization to Month 12)
- Change From Baseline in Weighted Impact ADDQoL Values at Month 12(Baseline; Month 12)
- Change From Baseline in DTSQs and DTSQc at Month 12(Baseline; Month 12)
- Mean Time to Change Infusion Site(Month 12)
- Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change(Month 12)
- Mean Times Per Week Participants Said They Were Eating to Avoid Going Low Due to Late Insulin Action(Month 12)