Randomized, Double-blind, Crossover, Pharmacokinetic (PK) and Glucodynamic (GD) Study of Continuous Subcutaneous Insulin Infusion (CSII) in Participants With Type 1 Diabetes Mellitus (T1DM)

NCT ID: NCT01275131

Last Updated: 2014-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2011-12-31

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.

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Stage 1: Insulin aspart first, then insulin aspart-rHuPH20

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.

Group Type: ACTIVE_COMPARATOR

Insulin aspart

Intervention Type: DRUG

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type: DRUG

Stage 1: Insulin aspart-rHuPH20 first, then insulin aspart

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.

Group Type: ACTIVE_COMPARATOR

Insulin aspart

Intervention Type: DRUG

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type: DRUG

Stage 3: Insulin aspart first, then insulin aspart + rHuPH20

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.

Group Type: ACTIVE_COMPARATOR

Insulin aspart

Intervention Type: DRUG

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type: DRUG

Stage 3: Insulin aspart + rHuPH20 first, then insulin aspart

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.

Group Type: ACTIVE_COMPARATOR

Insulin aspart

Intervention Type: DRUG

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type: DRUG

Interventions

Insulin aspart

Intervention Type: DRUG

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type: DRUG

Other Intervention Names

Novolog; PH20; Hylenex

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Halozyme Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Linda Morrow, MD

Role: PRINCIPAL_INVESTIGATOR

Profil Institute for Clinical Research, Inc.

Locations

Profil Institute for Clinical Research

Chula Vista, California, United States

Countries

United States

Other Identifiers

HALO-117-105

Identifier Type: -

Identifier Source: org_study_id