Type 1 Diabetes MellitusPhase 4NCT01526733
Randomized, Double Blind, 2 Way Crossover Study of CSII With, Versus Without, Pretreatment With Human Hyaluronidase
A Phase 4 study testing Recombinant human hyaluronidase PH20, Insulin aspart and Insulin lispro in people with Type 1 Diabetes Mellitus, run by Halozyme Therapeutics at 1 site in United States.
Trial summary
The purpose of this study is to evaluate consistency of accelerated insulin absorption and onset-of-action and shortened duration of action for bolus insulin infusions after pretreatment with 150 units (U) of Hylenex® (recombinant human hyaluronidase PH20 [rHuPH20]) injection at the time of infusion set insertion… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Recombinant human hyaluronidase PH20, Insulin aspart and Insulin lispro
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2011to Sep 2013
- Phase
- Phase 4
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females of age 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 ≥12 months. Nonsmoking means abstinence from cigarettes and cigars for 3 months and negative cotinine screening tests at screening.
- Body mass index (BMI) 18.0 to 35.0 kilograms per meter squared (kg/m²), inclusive.
- Glycosylated hemoglobin A1c (HbA1c) ≤10% based on local laboratory results.
- Fasting connecting peptide of insulin (C-peptide) <0.6 nanograms per milliliter (ng/mL).
- Current treatment with insulin <90 units per day (U/d).
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- Current use of rapid acting insulin analog.
- Routine use of CSII as the primary route of insulin administration for at least 3 months prior to screening
- Participants 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 the study protocol.
Who cannot join
- Known or suspected allergy to any component of any of the study drugs in this study.
- Previous enrollment in this study.
- Use of drugs that may interfere with the interpretation of study 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 (for example, coumadin or heparin) will be excluded.
- Use of any long-acting insulin injection within 72 hours of Study Day 1; participants will continue to refrain from use throughout the duration of the study (Phases I and II).
- 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 the Screening Visit(s) in this study.
- Pregnancy, breastfeeding, 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 Study Day 1.
Trial locations and contacts
1 site in 1 country.
United States1 site
Profil Institute for Clinical Research
Chula Vista, California, 91911
About this study
Official title: A Phase 4, Randomized, Double-Blind, 2-Way Crossover Study of Continuous Subcutaneous Insulin Infusion (CSII) With, Compared to Without, Pretreatment With Recombinant Human Hyaluronidase (rHuPH20)
The purpose of this study is to evaluate consistency of accelerated insulin absorption and onset-of-action and shortened duration of action for bolus insulin infusions after pretreatment with 150 units (U) of Hylenex® (recombinant human hyaluronidase PH20 [rHuPH20]) injection at the time of infusion set insertion compared to sham injection.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Sham Injection, Recombinant human hyaluronidase PH20, Insulin aspart, Insulin lispro
- Keywords
- Type 1 Diabetes, Continuous Subcutaneous Insulin Infusion (CSII)
- 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.
Sham InjectionDrug
Recombinant human hyaluronidase PH20Drug
Also called rHuPH20, PH20, Hylenex
Insulin aspartDrug
Also called Novolog, Aspart
Insulin lisproDrug
Also called Humalog, Lispro
| Study group | Role | What they receive |
|---|---|---|
| Insulin (Aspart or Lispro)-Sham | Sham comparator | In Phase I or Phase II of the study, participants received 0.15 units per kilogram (U/kg) insulin (either insulin aspart or insulin lispro) as a continuous subcutaneous insulin infusion (CSII) for 16 days, with sham injections administered prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16.
Each Phase was separated by a washout period of 5 to 21 days. Receives: Drug: Sham Injection; Drug: Insulin aspart; Drug: Insulin lispro |
| Insulin (Aspart or Lispro)-rHuPH20 | Experimental | In Phase I or Phase II of the study, participants received 0.15 U/kg insulin (either insulin aspart or insulin lispro) as a CSII for 16 days. Prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16, participants received a 1 mL (150 U) injection of recombinant human hyaluronidase (rHuPH20).
Each Phase was separated by a washout period of 5 to 21 days. Receives: Drug: Recombinant human hyaluronidase PH20; Drug: Insulin aspart; Drug: Insulin lispro |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early Insulin Exposure (%AUC[0-60])
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, and 60 minutes postdose during a euglycemic clamp.
Measured: 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose on Days 1 and 4
Secondary outcomes (6)
Maximum Glucose Infusion Rate (GIRmax)
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, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax)
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, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max)
Early and late tGIR50%max 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, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Time to 50% Total Glucose Infused (50%Gtot)
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, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Area Under the Glucose Concentration Curve (AUC[0-360])
Area under the glucose concentration curve from 0 to 360 minutes (AUC[0-360]) 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 and 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Duration of Insulin Action (AUMC[0-360]/AUC[0-360])
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]). AUCM is the total area under the first moment curve. First moment curve is obtained by plotting concentration-time versus time. It can be used to measure how long a drug stays in the body. 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; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2012 (estimated)
- Study startDec 2011
- Primary completionAug 2012
- Study completionSep 2013
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Halozyme Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Linda Morrow, MD, Principal investigator, Profil Institute for Clinical Research, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01526733
- Sponsor's protocol ID
- Halo-117-401
- Status last verified
- Feb 2019
- First submitted
- 31 Jan 2012
- Last updated
- 26 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 4, Randomized, Double-Blind, 2-Way Crossover Study of Continuous Subcutaneous Insulin Infusion (CSII) With, Compared to Without, Pretreatment With Recombinant Human Hyaluronidase (rHuPH20)
- ClinicalTrials.gov ID
- NCT01526733
- Acronym / sponsor ID
- Halo-117-401
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Type 1 Diabetes, Continuous Subcutaneous Insulin Infusion (CSII)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Halozyme TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Dec 2011
- Primary completion
- Aug 2012 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 6 Feb 2012 (estimated)
- Results
- Posted 29 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate consistency of accelerated insulin absorption and onset-of-action and shortened duration of action for bolus insulin infusions after pretreatment with 150 units (U) of Hylenex® (recombinant human hyaluronidase PH20 [rHuPH20]) injection at the time of infusion set insertion compared to sham injection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Insulin (Aspart or Lispro)-Sham | Sham comparator | Drug: Sham Injection, Drug: Insulin aspart, Drug: Insulin lisproIn Phase I or Phase II of the study, participants received 0.15 units per kilogram (U/kg) insulin (either insulin aspart or insulin lispro) as a continuous subcutaneous insulin infusion (CSII) for 16 days, with sham injections administered prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16. Each Phase was separated by a washout period of 5 to 21 days. |
| Insulin (Aspart or Lispro)-rHuPH20 | Experimental | Drug: Recombinant human hyaluronidase PH20, Drug: Insulin aspart, Drug: Insulin lisproIn Phase I or Phase II of the study, participants received 0.15 U/kg insulin (either insulin aspart or insulin lispro) as a CSII for 16 days. Prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16, participants received a 1 mL (150 U) injection of recombinant human hyaluronidase (rHuPH20). Each Phase was separated by a washout period of 5 to 21 days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Males or females of age 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 ≥12 months. Nonsmoking means abstinence from cigarettes and cigars for 3 months and negative cotinine screening tests at screening.
- Body mass index (BMI) 18.0 to 35.0 kilograms per meter squared (kg/m²), inclusive.
- Glycosylated hemoglobin A1c (HbA1c) ≤10% based on local laboratory results.
- Fasting connecting peptide of insulin (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 study.
- Previous enrollment in this study.
- Use of drugs that may interfere with the interpretation of study 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 (for example, coumadin or heparin) will be excluded.
- Use of any long-acting insulin injection within 72 hours of Study Day 1; participants will continue to refrain from use throughout the duration of the study (Phases I and II).
- 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 |
|---|---|---|
| Sham Injection | Drug | Insulin (Aspart or Lispro)-Sham |
| Recombinant human hyaluronidase PH20Also: rHuPH20, PH20, Hylenex | Drug | Insulin (Aspart or Lispro)-rHuPH20 |
| Insulin aspartAlso: Novolog, Aspart | Drug | Insulin (Aspart or Lispro)-Sham, Insulin (Aspart or Lispro)-rHuPH20 |
| Insulin lisproAlso: Humalog, Lispro | Drug | Insulin (Aspart or Lispro)-Sham, Insulin (Aspart or Lispro)-rHuPH20 |
Primary outcome
Early Insulin Exposure (%AUC[0-60])
Time frame: 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose on Days 1 and 4
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, and 60 minutes postdose during a euglycemic clamp.
6 secondary outcomes
Maximum Glucose Infusion Rate (GIRmax)
Time frame: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax)
Time frame: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max)
Time frame: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Time to 50% Total Glucose Infused (50%Gtot)
Time frame: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Area Under the Glucose Concentration Curve (AUC[0-360])
Time frame: 30 minutes and 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Duration of Insulin Action (AUMC[0-360]/AUC[0-360])
Time frame: 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Sponsor's WebsiteLink provided by the sponsor.
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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 4 study testing Recombinant human hyaluronidase PH20, Insulin aspart and Insulin lispro 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 9 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 26 Feb 2019. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 29 Sep 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]) (time frame: 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose on Days 1 and 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Feb 2019.