Type 1 Diabetes MellitusPhase 1NCT01275131

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

A Phase 1 study testing Insulin aspart and Recombinant human hyaluronidase PH20 (rHuPH20) in people with Type 1 Diabetes Mellitus, run by Halozyme Therapeutics at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Type 1 Diabetes Mellitus
What is being tested?: Insulin aspart and Recombinant human hyaluronidase PH20 (rHuPH20)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 45 participants
Where: 1 siteUnited States
Study dates: Jan 2011to Dec 2011
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Profil Institute for Clinical Research
Chula Vista, California, 91911

Other trials in United States

About this study

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)

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
Being tested: Insulin aspart, Recombinant human hyaluronidase PH20 (rHuPH20)
Keywords: Insulin analog, Type 1 diabetes mellitus, Pharmacokinetic, Glucodynamic, Phase 1
Medical subject headings: Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Insulin aspartDrug
Also called Novolog
Recombinant human hyaluronidase PH20 (rHuPH20)Drug
Also called PH20, Hylenex

Study groups in NCT01275131
Study group	Role	What they receive
Stage 1: Insulin aspart first, then insulin aspart-rHuPH20	Active comparator	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. Receives: Drug: Insulin aspart; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Stage 1: Insulin aspart-rHuPH20 first, then insulin aspart	Active comparator	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. Receives: Drug: Insulin aspart; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Stage 3: Insulin aspart first, then insulin aspart + rHuPH20	Active comparator	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. Receives: Drug: Insulin aspart; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Stage 3: Insulin aspart + rHuPH20 first, then insulin aspart	Active comparator	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. Receives: Drug: Insulin aspart; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 10 minutes predose up to 60 minutes postdose
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.
Measured: 10 minutes predose up to 60 minutes postdose on Days 2/7, 3/8, and 5/10

Secondary outcomes (12)

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.
Measured: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8
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.
Measured: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10
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.
Measured: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8
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.
Measured: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10
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.
Measured: 0 up to 360 minutes postdose on day 2/6 and Day 4/8
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.
Measured: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10
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.
Measured: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8
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.
Measured: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10
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.
Measured: 30 minutes predose up to 360 minutes postdose on Day 2/6 and Day 4/8
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.
Measured: 30 minutes predose up to 360 minutes postdose Days 2/7, 3/8, and 5/10
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.
Measured: 10 minutes predose up to 360 minutes postdose on Day 2/6 and Day 4/8
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.
Measured: 10 minutes predose up to 360 minutes postdose on Days 2/7, 3/8, and 5/10

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2011Dec 2011

First posted12 Jan 2011 (estimated)
Study startJan 2011
Primary completionDec 2011
Study completionDec 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 45 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01275131
Sponsor's protocol ID: HALO-117-105
Status last verified: Jun 2014
First submitted: 10 Jan 2011
Last updated: 25 Jul 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 25 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT01275131
Acronym / sponsor ID: HALO-117-105
Conditions: Type 1 Diabetes Mellitus
Keywords: Insulin analog, Type 1 diabetes mellitus, Pharmacokinetic, Glucodynamic, Phase 1
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 45 participants (actual)
Lead sponsor: Halozyme TherapeuticsIndustry (pharma, biotech, devices)
Study start: Jan 2011
Primary completion: Dec 2011 (actual)
Study completion: Dec 2011 (actual)
First posted: 12 Jan 2011 (estimated)
Results: Posted 25 Jul 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 4

Arm	Type	Receives
Stage 1: Insulin aspart first, then insulin aspart-rHuPH20	Active comparator	Drug: Insulin aspart, Drug: Recombinant human hyaluronidase PH20 (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.
Stage 1: Insulin aspart-rHuPH20 first, then insulin aspart	Active comparator	Drug: Insulin aspart, Drug: Recombinant human hyaluronidase PH20 (rHuPH20)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.
Stage 3: Insulin aspart first, then insulin aspart + rHuPH20	Active comparator	Drug: Insulin aspart, Drug: Recombinant human hyaluronidase PH20 (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.
Stage 3: Insulin aspart + rHuPH20 first, then insulin aspart	Active comparator	Drug: Insulin aspart, Drug: Recombinant human hyaluronidase PH20 (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 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.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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).

Key exclusion criteria (10 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Insulin aspartAlso: Novolog	Drug	Stage 1: Insulin aspart first, then insulin aspart-rHuPH20, Stage 1: Insulin aspart-rHuPH20 first, then insulin aspart, Stage 3: Insulin aspart + rHuPH20 first, then insulin aspart, Stage 3: Insulin aspart first, then insulin aspart + rHuPH20
Recombinant human hyaluronidase PH20 (rHuPH20)Also: PH20, Hylenex	Drug	Stage 1: Insulin aspart first, then insulin aspart-rHuPH20, Stage 1: Insulin aspart-rHuPH20 first, then insulin aspart, Stage 3: Insulin aspart + rHuPH20 first, then insulin aspart, Stage 3: Insulin aspart first, then insulin aspart + rHuPH20

Primary outcome

Early Insulin Exposure (%AUC[0-60]), Stage 1
Time frame: 10 minutes predose up to 60 minutes postdose
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.
Early Exposure to Insulin (%AUC[0-60]), Stage 3
Time frame: 10 minutes predose up to 60 minutes postdose on Days 2/7, 3/8, and 5/10
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.

12 secondary outcomes

Maximum Glucose Infusion Rate (GIRmax), Stage 1
Time frame: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8
Maximum Glucose Infusion Rate (GIRmax), Stage 3
Time frame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10
Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 1
Time frame: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8
Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 3
Time frame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10
Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 1
Time frame: 0 up to 360 minutes postdose on day 2/6 and Day 4/8
Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 3
Time frame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10
Time to 50% Total Glucose Infused (50%Gtot), Stage 1
Time frame: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8
Time to 50% Total Glucose Infused (50%Gtot), Stage 3
Time frame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10
Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 1
Time frame: 30 minutes predose up to 360 minutes postdose on Day 2/6 and Day 4/8
Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 3
Time frame: 30 minutes predose up to 360 minutes postdose Days 2/7, 3/8, and 5/10
Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 1
Time frame: 10 minutes predose up to 360 minutes postdose on Day 2/6 and Day 4/8
Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 3
Time frame: 10 minutes predose up to 360 minutes postdose on Days 2/7, 3/8, and 5/10

Results and safety

Results posted to the registry on 25 Jul 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Stage 1: Insulin Aspart First, Then Insulin Aspart-rHuPH20	11	9
Stage 1: Insulin Aspart-rHuPH20 First, Then Insulin Aspart	9	9
Stage 3: Insulin Aspart First, Then Insulin Aspart + rHuPH20	13	10
Stage 3: Insulin Aspart + rHuPH20 First, Then Insulin Aspart	12	10

Primary outcome: Early Insulin Exposure (%AUC[0-60]), Stage 1

Time frame: 10 minutes predose up to 60 minutes postdose. Mean (Standard Deviation). Unit: Percentage of AUC(0-360)

Measure	Stage 1: Insulin Aspart Alone n = 16	Stage 1: Insulin Aspart-rHuPH20 n = 16
Stage 1, Day 2/6	20.99 (6.37)	34.94 (9.48)
Stage 1, Day 4/8	32.83 (14.66)	50.97 (13.91)

Stage 1: Insulin Aspart Alone vs Stage 1: Insulin Aspart-rHuPH20: Least Squares Mean Difference: 13.95 (90% CI 7.37 to 20.54), p = 0.0009, Mixed Models Analysis
Stage 1: Insulin Aspart Alone vs Stage 1: Insulin Aspart-rHuPH20: Least Squares Mean Difference: 18.14 (90% CI 11.55 to 24.72), p <0.0001, Mixed Models Analysis

Population analysed: Participants who completed all study periods within a given stage with evaluable early insulin exposure (%AUC\[0-60\]) data.

Primary outcome: Early Exposure to Insulin (%AUC[0-60]), Stage 3

Time frame: 10 minutes predose up to 60 minutes postdose on Days 2/7, 3/8, and 5/10. Mean (Standard Deviation). Unit: Percentage of AUC(0-360)

Measure	Stage 3: Insulin Aspart Alone n = 17	Stage 3: Insulin Aspart + rHuPH20 n = 17
Stage 3, Day 2/7	15.70 (6.38)	32.11 (10.91)
Stage 3, Day 3/8	22.29 (5.43)	36.39 (9.43)
Stage 3, Day 5/10	27.31 (10.49)	32.64 (11.32)

Stage 3: Insulin Aspart Alone vs Stage 3: Insulin Aspart + rHuPH20: Least Squares Mean Difference: 16.41 (90% CI 11.86 to 20.97), p <0.0001, Mixed Models Analysis
Stage 3: Insulin Aspart Alone vs Stage 3: Insulin Aspart + rHuPH20: Least Squares Mean Difference: 14.10 (90% CI 9.55 to 18.65), p <0.0001, Mixed Models Analysis
Stage 3: Insulin Aspart Alone vs Stage 3: Insulin Aspart + rHuPH20: Least Squares Mean Difference: 5.32 (90% CI 0.77 to 9.88), p = 0.0552, Mixed Models Analysis

Population analysed: Participants who completed all periods of study within a given stage with evaluable %AUC(0-60) data.

12 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Stage 1: Insulin Aspart	0 of 20 (0%)	16 of 20 (80%)	Not reported
Stage 1: Insulin Aspart-rHuPH20	0 of 18 (0%)	13 of 18 (72.2%)	Not reported
Stage 3: Insulin Aspart	0 of 23 (0%)	14 of 23 (60.9%)	Not reported
Stage 3: Insulin Aspart + rHuPH20	0 of 22 (0%)	12 of 22 (54.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Linda Morrow, MD principal investigator

Profil Institute for Clinical Research, Inc.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Insulin aspart and Recombinant human hyaluronidase PH20 (rHuPH20) in people with Type 1 Diabetes Mellitus, run by Halozyme Therapeutics at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Early Insulin Exposure (%AUC[0-60]), Stage 1 (time frame: 10 minutes predose up to 60 minutes postdose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01275131.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2014.