Clinical trial NCT01848990: CONSISTENT 1: Metabolic and Safety Outcomes of Hylenex Recombinant (Hyaluronidase Human Injection) Preadministered at CSII Infusion Site in Participants With Type 1 Diabetes Mellitus (T1DM)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 1 Diabetes Mellitus
Keywords: Type 1 Diabetes Mellitus
Sub Cutaneous Insulin Infusion
Rapid Acting Analog Insulin
Hylenex
Halozyme
Phase 4
Lead sponsor: Halozyme Therapeutics
Sponsor class: INDUSTRY
First posted: 2013-05-08
Enrollment: 456
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female of age 18 years or older with a history of T1DM for at least 12 months
2. Glycosylated hemoglobin (HbA1c) 6.5% to 9.5% (inclusive) based on central laboratory results
3. Fasting C-peptide \<0.6 nanograms per milliliter (ng/mL)
4. 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
5. Current treatment at the time of screening with insulin \<300 units per day (U/day)
6. 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.
7. 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:

1. Type 2 diabetes
2. Known or suspected allergy to any component of any of the study drugs in this study
3. 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
4. History of transmural myocardial infarction, congestive heart failure and uncontrolled hypertension (diastolic blood pressure \[BP\] consistently \>100 millimeters of mercury \[mmHg\]) are exclusionary
5. 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
6. 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
7. As judged by the Investigator, clinically significant findings in routine laboratory data at screening
8. 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.
9. Hypoglycemic unawareness of such severity as to impede the participant's ability to comply with protocol procedures, as judged by the Investigator.
10. Current addiction to alcohol or substance abuse as determined by the Investigator.
11. Pregnancy, breast-feeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, intra-uterine device \[IUD\], oral or injectable contraceptives, and/or barrier methods). Abstinence alone is not considered an adequate contraceptive measure for the purposes of this study.
12. Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study

Primary outcomes:
measure: Change From Baseline to 6 Months in Glycosylated Hemoglobin (HbA1c)
timeFrame: Baseline; 6 Months
measure: Change From Baseline to 12 Months in HbA1c
timeFrame: Baseline; 12 Months
Secondary outcomes:
measure: Rates of Hypoglycemia Events (HE) to Month 6
timeFrame: After Month 1 up to Month 6
measure: Rates of HEs to Month 12
timeFrame: After Month 1 up to Month 12
measure: Rates of Hyperglycemia Events to Month 6
timeFrame: After Month 1 up to Month 6
measure: Rates of Hyperglycemia Events to Month 12
timeFrame: After Month 1 up to Month 12
measure: Mean Glucose Excursions at 6 Months
timeFrame: After Month 1 up to Month 6
measure: Mean Glucose Excursions at 12 Months
timeFrame: After Month 1 up to Month 12
measure: Standard Deviation of Self-Monitoring Blood Glucose Values at 6 Months
timeFrame: After Month 1 up to Month 6
measure: Standard Deviation of Self-Monitoring Blood Glucose Values at 12 Months
timeFrame: After Month 1 up to Month 12
measure: Number of Participants Achieving HbA1c <7.0% and HbA1c ≤6.5% at Month 12
timeFrame: Month 12
measure: Change From Baseline in Body Weight to Month 12
timeFrame: Baseline; Week 2; Months 1, 2, 3, 4, 6, 9, and 12
measure: Average of Daily Insulin Doses (Bolus, Basal, and Total)
timeFrame: from Randomization up to Month 12
measure: Average Carbohydrate Factor (CarbF) Values
timeFrame: Month 1 to Month 12
measure: Average Correction Factor (CorrF) Values
timeFrame: Month 1 to Month 12
measure: Average of Bolus Times Relative to Meal Times
timeFrame: Month 1 to Month 12
measure: Average Glucose, Median Glucose, and Average Daily Standard Deviation
timeFrame: Randomization to Month 12
measure: 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
timeFrame: Randomization to Month 12
measure: 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
timeFrame: Randomization to Month 12
measure: Change From Baseline in Weighted Impact ADDQoL Values at Month 12
timeFrame: Baseline; Month 12
measure: Change From Baseline in Average Weighted Impact ADDQoL Values at Month 12
timeFrame: Baseline; Month 12
measure: Change From Baseline in DTSQs and DTSQc at Month 12
timeFrame: Baseline; Month 12
measure: Mean Time to Change Infusion Site
timeFrame: Month 12
measure: Mean Additional Time for Hylenex Pre-administration
timeFrame: Month 12
measure: Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change
timeFrame: Month 12
measure: Number of Participants With the Indicated Responses to the Device Handling Questions
timeFrame: Month 12
measure: Mean Times Per Week Participants Said They Were Eating to Avoid Going Low Due to Late Insulin Action
timeFrame: Month 12
Other outcomes:
Locations:
city: Concord
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: California
city: Encino
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: California
city: Escondido
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: California
city: Greenbrae
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: California
city: La Jolla
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: California
city: San Mateo
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: California
city: Aurora
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Colorado
city: Hollywood
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Florida
city: Miami
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Florida
city: Miami
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Florida
city: Atlanta
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Georgia
city: Roswell
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Georgia
city: Idaho Falls
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Idaho
city: Des Moines
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Iowa
city: Wichita
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Kansas
city: Lexington
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Kentucky
city: Hyattsville
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Maryland
city: Rockville
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Maryland
city: Detroit
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Michigan
city: Minneapolis
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Minnesota
city: Butte
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Montana
city: Henderson
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Nevada
city: Las Vegas
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Nevada
city: New Hyde Park
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: New York
city: Asheville
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: North Carolina
city: Durham
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: North Carolina
city: Morehead City
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: North Carolina
city: Cincinnati
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Ohio
city: Portland
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Oregon
city: Bartlett
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Tennessee
city: Chattanooga
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Tennessee
city: Austin
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Texas
city: Dallas
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Texas
city: Round Rock
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Texas
city: San Antonio
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Texas
city: Olympia
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Washington
city: Renton
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Washington
city: Seattle
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Washington
city: Madison
country: United States
facility: For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
state: Wisconsin
Study officials:
affiliation: Halozyme Therapeutics
name: Douglas Muchmore, MD
role: STUDY_DIRECTOR
References: