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 Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01275131
• Other study ID #: HALO-117-105
• Status: Completed
• Phase: Phase 1
• First received: January 10, 2011
• Last updated: June 26, 2014
• Start date: January 2011
• Est. completion date: December 2011

Study information

• Verified date: June 2014
• Source: Halozyme Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Insulin aspart

• Recombinant human hyaluronidase PH20 (rHuPH20)

Locations

Country	Name	City	State
United States	Profil Institute for Clinical Research	Chula Vista	California

Sponsors (1)

Lead Sponsor	Collaborator
Halozyme Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early Insulin Exposure (%AUC[0-60]), Stage 1	Early insulin exposure, defined as the percentage of total insulin exposure (area under the insulin concentration curve [AUC{0-360}]) that occurs within the first hour following bolus dose of insulin during the 2 euglycemic clamps is presented. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 120, 150, 180, 240, 300, and 360 minutes postdose during the euglycemic clamp.	10 minutes predose up to 60 minutes postdose	No
Primary	Early Exposure to Insulin (%AUC[0-60]), Stage 3	Early insulin exposure, defined as the percentage of total insulin exposure (area under the insulin concentration curve [AUC{0-360}) that occurs within the first hour following bolus dose of insulin during the 2 euglycemic clamps is presented. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 120, 150, 180, 240, 300, and 360 minutes postdose during the euglycemic clamp.	10 minutes predose up to 60 minutes postdose on Days 2/7, 3/8, and 5/10	No
Secondary	Maximum Glucose Infusion Rate (GIRmax), Stage 1	Maximum glucose infusion rates (GIRmax) for Stage1 are presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.	0 up to 360 minutes postdose on Day 2/6 and Day 4/8	No
Secondary	Maximum Glucose Infusion Rate (GIRmax), Stage 3	Maximum glucose infusion rates (GIRmax) for Stage 3 are presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.	0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10	Yes
Secondary	Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 1	Time to first occurrence of maximum glucose infusion rate (tGIRmax) for Stage 1 is presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.	0 up to 360 minutes postdose on Day 2/6 and Day 4/8	No
Secondary	Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 3	Time to first occurrence of maximum glucose infusion rate (tGIRmax) for Stage 3 is presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.	0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10	No
Secondary	Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 1	Early and late times to 50% maximum glucose infusion rate (tGIR50%max) for Stage 1 are presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.	0 up to 360 minutes postdose on day 2/6 and Day 4/8	No
Secondary	Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 3	Early and late time to 50% maximum glucose infusion rates (tGIR50%max) for Stage 3 studies are presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.	0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10	No
Secondary	Time to 50% Total Glucose Infused (50%Gtot), Stage 1	Time to 50% total glucose infused (50%Gtot) is presented for Stage 1. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.	0 up to 360 minutes postdose on Day 2/6 and Day 4/8	No
Secondary	Time to 50% Total Glucose Infused (50%Gtot), Stage 3	Time to 50% of total glucose infused (50%Gtot) is presented for Stage 3. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.	0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10	Yes
Secondary	Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 1	Area under the glucose concentration curve for 0 to 360 minutes (AUC[0-360]) from Stage 1 is presented. Blood samples were collected 30 and 10 minutes prior to insulin bolus and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.	30 minutes predose up to 360 minutes postdose on Day 2/6 and Day 4/8	No
Secondary	Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 3	Area under the glucose concentration curve from 0 to 360 minutes (AUC[0-360]) for Stage 3 studies is presented. Blood samples were collected 30 and 10 minutes prior to insulin bolus and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.	30 minutes predose up to 360 minutes postdose Days 2/7, 3/8, and 5/10	No
Secondary	Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 1	Duration of insulin action was calculated by dividing the area under the first moment curve (AUMC[0-360]) by the area under the concentration versus time curve (AUC[0-360]) for Stage 1. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.	10 minutes predose up to 360 minutes postdose on Day 2/6 and Day 4/8	No
Secondary	Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 3	Duration of insulin action was calculated by dividing the area under the first moment curve (AUMC[0-360]) by the area under the concentration versus time curve (AUC[0-360]) for Stage 3. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.	10 minutes predose up to 360 minutes postdose on Days 2/7, 3/8, and 5/10	No