Clinical trial NCT01275131: Randomized, Double-blind, Crossover, Pharmacokinetic (PK) and Glucodynamic (GD) Study of Continuous Subcutaneous Insulin Infusion (CSII) in Participants With Type 1 Diabetes Mellitus (T1DM)
Official title: Randomized, Double-Blind, Pharmacokinetic (PK) and Glucodynamic (GD) Crossover Study of Continuous Subcutaneous Insulin Infusion (CSII) of Rapid Acting Insulin Analogs With and Without Recombinant Human Hyaluronidase (rHuPH20)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 1 Diabetes Mellitus
Keywords: Insulin analog
Type 1 diabetes mellitus
Pharmacokinetic
Glucodynamic
Phase 1
Lead sponsor: Halozyme Therapeutics
Sponsor class: INDUSTRY
First posted: 2011-01-12
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to determine if recombinant human hyaluronidase PH20 (rHuPH20) will change the exposure and action of approved insulin analogs when given by continuous subcutaneous insulin infusion (CSII) in participants with Type 1 diabetes mellitus (T1DM).

This study is divided into Stage 1, 2, and 3. Stage 3 was started chronologically before Stage 2 and, prior to performing Stage 2, the Sponsor made the decision to terminate Stage 2. Stage 2 was not initiated due to a strategic business decision and termination was not based on safety or efficacy concerns. No participants were enrolled in Stage 2.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.
3. Body mass index (BMI) 18.0 to 35.0 kilograms per meter squared (kg/m\^2), inclusive.
4. Glycosylated hemoglobin A1c (HbA1c) ≤10 % based on local laboratory results.
5. Fasting C-peptide \<0.6 nanograms per milliliter (ng/mL).
6. Current treatment with insulin \<90 units per day (U/d).
7. Routine use of continuous subcutaneous insulin infusion (CSII) as the primary route of insulin administration.
8. 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:

1. Known or suspected allergy to any component of any of the study drugs in this trial.
2. Previous enrollment in this trial (Exception: participants in Stage 1 are permitted to participate in Stage 2).
3. 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.
4. Use of any long-acting insulin injection within 72 hours of Stage 1 or Stage 3.
5. Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator.
6. Current addiction to alcohol or substances of abuse as determined by the Investigator.
7. 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.
8. 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).
9. Symptomatic gastroparesis.
10. Receipt of any investigational drug within 4 weeks of Stage 1 or Stage 2.

Primary outcomes:
measure: Early Insulin Exposure (%AUC[0-60]), Stage 1
timeFrame: 10 minutes predose up to 60 minutes postdose
measure: Early Exposure to Insulin (%AUC[0-60]), Stage 3
timeFrame: 10 minutes predose up to 60 minutes postdose on Days 2/7, 3/8, and 5/10
Secondary outcomes:
measure: Maximum Glucose Infusion Rate (GIRmax), Stage 1
timeFrame: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8
measure: Maximum Glucose Infusion Rate (GIRmax), Stage 3
timeFrame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10
measure: Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 1
timeFrame: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8
measure: Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 3
timeFrame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10
measure: Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 1
timeFrame: 0 up to 360 minutes postdose on day 2/6 and Day 4/8
measure: Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 3
timeFrame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10
measure: Time to 50% Total Glucose Infused (50%Gtot), Stage 1
timeFrame: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8
measure: Time to 50% Total Glucose Infused (50%Gtot), Stage 3
timeFrame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10
measure: Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 1
timeFrame: 30 minutes predose up to 360 minutes postdose on Day 2/6 and Day 4/8
measure: Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 3
timeFrame: 30 minutes predose up to 360 minutes postdose Days 2/7, 3/8, and 5/10
measure: Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 1
timeFrame: 10 minutes predose up to 360 minutes postdose on Day 2/6 and Day 4/8
measure: Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 3
timeFrame: 10 minutes predose up to 360 minutes postdose on Days 2/7, 3/8, and 5/10
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research
state: California
Study officials:
affiliation: Profil Institute for Clinical Research, Inc.
name: Linda Morrow, MD
role: PRINCIPAL_INVESTIGATOR
References: