Randomized, Double-blind, Crossover, Pharmacokinetic (PK) and Glucodynamic (GD) Study of Continuous Subcutaneous Insulin Infusion (CSII) in Participants With Type 1 Diabetes Mellitus (T1DM)
Type 1 Diabetes Mellitus
About this trial
This is an interventional basic science trial for Type 1 Diabetes Mellitus focused on measuring Insulin analog, Type 1 diabetes mellitus, Pharmacokinetic, Glucodynamic, Phase 1
Eligibility Criteria
Inclusion Criteria:
- Male or female aged 18 to 65 years, inclusive. Females of child-bearing potential must use a standard and effective means of birth control for the duration of the study.
- Non-smoking participants with Type 1 diabetes mellitus (T1DM) treated with insulin for greater than or equal to 12 months. Non-smoking means abstinence from cigarettes and cigars for 3 months and negative cotinine screening tests.
- Body mass index (BMI) 18.0 to 35.0 kilograms per meter squared (kg/m^2), inclusive.
- Glycosylated hemoglobin A1c (HbA1c) ≤10 % based on local laboratory results.
- Fasting C-peptide <0.6 nanograms per milliliter (ng/mL).
- Current treatment with insulin <90 units per day (U/d).
- Routine use of continuous subcutaneous insulin infusion (CSII) as the primary route of insulin administration.
- Participant 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:
- Known or suspected allergy to any component of any of the study drugs in this trial.
- Previous enrollment in this trial (Exception: participants in Stage 1 are permitted to participate in Stage 2).
- Use of drugs that may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia. Participants taking maintenance doses of blood thinners (eg, Coumadin or heparin) will be excluded.
- Use of any long-acting insulin injection within 72 hours of Stage 1 or Stage 3.
- Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator.
- Current addiction to alcohol or substances of abuse as determined by the Investigator.
- Blood donation or phlebotomy (>500 milliliters [mL]) within the previous 8 weeks of Screening. This applies both to new participants and to participants who have participated in Stage 1 and who wish to continue in Stage 2.
- 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, or barrier methods).
- Symptomatic gastroparesis.
- Receipt of any investigational drug within 4 weeks of Stage 1 or Stage 2.
Sites / Locations
- Profil Institute for Clinical Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Stage 1: Insulin aspart first, then insulin aspart-rHuPH20
Stage 1: Insulin aspart-rHuPH20 first, then insulin aspart
Stage 3: Insulin aspart first, then insulin aspart + rHuPH20
Stage 3: Insulin aspart + rHuPH20 first, then insulin aspart
Participants first received 0.15 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4. After a 5- to 14-day washout period, participants received 0.15 U/kg insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) coadministered as a CSII, for 4 days (Days 5-8; Period 2), including during a 6-hr euglycemic clamp on Days 6 and 8.
Participants first received 0.15 units per kilogram (U/kg) insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) coadministered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4. After a 5- to 14-day washout period, participants received 0.15 U/kg insulin aspart alone as a CSII, for 4 days (Days 5-8; Period 2), including during a 6-hr euglycemic clamp on Days 6 and 8.
Participants first received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5. On Day 2 only, a sham injection was administered 2.5 hr prior to the 6-hr euglycemic clamp. After a 5- to 14-day washout period, participants received 0.12 U/kg insulin aspart administered as a CSII, for 5 days (Days 6-10; Period 2), including during a 6-hr euglycemic clamp on Days 7, 8, and 10. On Day 7 only, a 1.0-milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the 6-hr euglycemic clamp.
Participants first received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5; Period 1), including during a 6- hour (hr) euglycemic clamp on Days 2, 3, and 5. On Day 2 only, a 1.0-milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the euglycemic clamp . After a 5- to 14- day washout period, participants received 0.12 U/kg insulin aspart administered as a CSII, for 5 days (Days 6-10; Period 2), including during a 6-hr euglycemic clamp on Days 7, 8, and 10. On Day 7 only, a sham injection was administered 2.5 hr prior to the 6-hour euglycemic clamp.