Study of HDV Insulin Versus Insulin in Type 1 Diabetes Subjects (ISLE-1) (ISLE-1)
|ClinicalTrials.gov Identifier: NCT02794155|
Recruitment Status : Completed
First Posted : June 8, 2016
Last Update Posted : July 31, 2018
|Condition or disease||Intervention/treatment||Phase|
|Type 1 Diabetes Mellitus||Drug: HDV Insulin Lispro Drug: Insulin LISPRO||Phase 2|
This will be a Phase 2b, multicenter, randomized, double blind, titration clinical study, evaluating the efficacy and safety in the HDV Insulin Lispro Group versus Insulin Lispro Group in patients with type 1 diabetes over a 26 week treatment period. The patients will be randomized using a centrally allocated randomization scheme to 1 of the 2 treatment arms in an overall 2:1 scheme (HDV Insulin Lispro: Insulin Lispro). Both arms will receive the randomized treatment in combination with glargine or detemir.
SCREENING (Visit 1, Week -4 to -1) Patients will arrive for Screening following an 8 hour fast. During Screening, patients will sign the informed consent form, be reviewed for inclusion/exclusion, and provide medical history, concomitant medications, and demographics. They will have a brief physical exam and provide vital signs. Safety hematology/chemistry/urinalysis (with liver enzymes) will include infectious serology, and serum pregnancy test for women of childbearing potential. An ECG will be performed and patients will provide samples for HbA1c determination.
Patients taking lispro/glargine or lispro/detemir at the time of Screening and who meet all eligibility criteria will proceed to Visit 2 (Week -1).
TREATMENT PERIOD Visit 1a (Week -2) will be required only if a patient must convert to lispro prior to Visit 3 (Week 0, randomization). Patients taking non-lispro/glargine or non-lispro/detemir or using an insulin pump will be converted to lispro/glargine or lispro/detemir (respectively) using equivalent insulin units, then proceed to Visit 2 (Week -1) after 1 week on the new regimen. At Visit 2 (Week -1), patients will receive the CGM and be trained on its use. Patients will also have their first Mixed Meal Tolerance Test (MMTT) during Visit 2 (Week -1) accompanied by monitoring of blood ketones pre- and post-ingestion. CGM and MMTT will be repeated at Visits 9 (Week 12) and 14 (Week 25). A diary, glucose meter, and supplies will also be provided at Visit 2 (Week -1). Patients will be instructed on how to perform self-monitored blood glucose measurements (SMBG). During Visit 3 (Week 0), eligible patients will be randomized by IWRS to either treatment arm (Test Group or Control Group) and baseline data will be collected. All visits will include progress reviews and safety procedures. Safety hematology/chemistry/ urinalysis at Visits 2 (Week -1), 10 (Week 13), 14 (Week 25) and 16 (Week 27) will include liver enzymes. At Visits 6 (Week 5) and 12 (Week 19), liver enzymes will be the only chemistry safety tests performed. The only chemistry safety tests performed at Visits 2 (Week -1), 9 (Week 12), and 14 (Week 25) will be blood ketones; these will be measured at baseline and 3 hours after the MMTT. HbA1c will be measured at Visits 3 (Week 0), 4 (Week 1), 7 (Week 7), 10 (Week 13), 12 (Week 19), and 15 (Week 26). Fasting blood glucose will be measured at Visits 3 (Week 0), 10 (Week 13), and 15 (Week 26). An in-clinic urine pregnancy test will be performed at all visits for women of childbearing potential. MRI will be performed at Visits 3 (Week 0) and 14 (Week 25) for approximately 20% of patients in each treatment arm. MRI may also be performed on a case-by-case basis in the event of abnormal liver enzyme results. Patients will receive weekly telephone calls from the PI or a designee to discuss insulin dosing and titration.
FOLLOW-UP Visit 16 (Week 27) is a safety follow-up visit which will include a physical exam. Safety hematology/chemistry/ urinalysis (including liver enzymes) will include a urine pregnancy test for women of childbearing potential.
Concomitant medications, vital signs, and adverse events will be recorded throughout the entire study period.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||157 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Phase 2b, Multicenter, Randomized, Double Blind, Titration Trial for Efficacy and Safety of HDV Insulin Lispro in Combination With a Basal Insulin Versus Insulin Lispro in Combination With a Basal Insulin in Patients With Type 1 Diabetes|
|Study Start Date :||June 2016|
|Actual Primary Completion Date :||April 28, 2018|
|Actual Study Completion Date :||June 15, 2018|
Experimental: Test Group
HDV Insulin Lispro subcutaneous, pre-prandial dosing, 26 week treatment period
Drug: HDV Insulin Lispro
HDV Insulin Lispro: ~1% of the Insulin Lispro is bound to HDV (Hepatocyte Directed Vesicle)
Other Name: HDV Humalog
Active Comparator: Control Group
Insulin Lispro subcutaneous, Pre-prandial dosing, 26 week treatment period
Drug: Insulin LISPRO
Insulin Lispro: no bound insulin
Other Name: Humalog
- Change in HbA1c [ Time Frame: 26 weeks ]Change in HbA1c from Week 0 to Week 13, from Week 0 to Week 26, and from Week 13 to Week 26
- Change in fasting blood glucose glucose levels [ Time Frame: 26 weeks ]Difference in fasting blood glucose levels Mean Mixed Tolerance Test AUC,
- Hypoglycemia occurrences by category: Severe, Documented Symptomatic, and Asymptomatic Hypoglycemia [ Time Frame: 26 weeks ]Comparison of frequency and severity of hypoglycemia
- Number of Patients with Adverse Events [ Time Frame: 26 weeks ]• To demonstrate the safety of HDV insulin lispro over 26 weeks of administration.
- Change in total insulin usage [ Time Frame: 26 weeks ]• Comparison of basal and bolus insulin doses as a mean of 3 days of use at Week 0 and at 13 and 26 weeks, and comparison of total bolus insulin dosing at end of run-in phase to the end of the 13 week treatment period, and from the 13 week treatment period to the 26 week treatment period.
- Change in Body Weight [ Time Frame: 26 weeks ]Comparison of change in body weight (in Kilograms) from baseline through week 26.
- Mean Mixed Meal Tolerance Test [ Time Frame: 13 and 26 weeks ]Comparison of mean mixed meal tolerance test (MMTT) (AUC0-120) from Week 0 (baseline) to Week 13, from Week 0 (baseline) to Week 26, and from Week 13 to Week 26
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02794155
|Principal Investigator:||David Klonoff, MD||Mills-Peninsula Health Services|