Type 1 Diabetes MellitusPhase 2NCT00774800

Phase II Pharmacokinetics Study of Humalog and Humulin-R With and Without rHuPH20 in Type 1 Diabetes Mellitus

A Phase 2 study testing Humalog, Humulin-R 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

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Type 1 Diabetes Mellitus
What is being tested?: Humalog, Humulin-R 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: 22 participants
Where: 1 siteUnited States
Study dates: Oct 2008to Mar 2009
Phase: Phase 2
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

Male or female 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.
Participants with Type 1 diabetes mellitus treated with insulin for greater than or equal to 12 months.
Body mass index (BMI) 18.0 to 29.0 kilograms per meter squared (kg/m^2), inclusive.
Glycosylated hemoglobin A1c (HbA1c) less than or equal to 10% based on local laboratory results.
Fasting C-peptide less than 0.6 nanograms per milliliter (ng/mL).
Current treatment with insulin less than 1.2 units per kilogram per day (U/kg/day).
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 injections 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.
A participant who has proliferative retinopathy or maculopathy, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.
Clinically significant (as judged by the Investigator) active disease of the gastrointestinal, cardiovascular (including a history of arrhythmia or conduction delays on electrocardiogram [ECG]), hepatic, neurological, renal, genitourinary, or hematological systems, or uncontrolled hypertension (diastolic blood pressure greater than or equal to 100 millimeters of mercury [mmHg] and/or systolic blood pressure greater than or equal to 160 mmHg after 5 minutes in the supine position).
History of any illness or disease that in the opinion of the Investigator might confound the results of the trial or pose additional risk in administering the study drugs to the participant.
Clinically significant findings (as judged by the Investigator) in routine laboratory data, including anemia with hemoglobin less than lower limits of normal at screening.

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Use of drugs which 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.
Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator.
Current addiction to alcohol or substances of abuse as determined by the Investigator.
Blood donation (>500 milliliters [mL]) within the 9 weeks prior to first day of dosing on study.
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).
Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation.
Symptomatic gastroparesis.
History or evidence of use of any tobacco- or nicotine-containing product within 6 months of screening or screening quantitative urine nicotine concentration >50 ng/mL.
Receipt of any investigational drug within 4 weeks of first day of dosing in this study.
Any condition (intrinsic or extrinsic) that in the judgment of the Investigator will interfere with trial participation or evaluation of data.

Trial locations and contacts

1 site in 1 country.

United States1 site

Profil Institute for Clinical Research, Inc.
Chula Vista, California, 91911

Other trials in United States

About this study

Official title: Phase II Study Evaluating Pharmacokinetics and Postprandial Glycemic Response of Subcutaneously Injected Humalog and Humulin R With/Without Co-Injected Recombinant Human Hyaluronidase Following Liquid Meal in Type1 Diabetes Mellitus Patients

Humalog and Humulin-R (recombinant human insulin) are Food and Drug Administration (FDA) approved medications for the treatment of diabetes mellitus. Recombinant human hyaluronidase PH20 (rHuPH20) is approved by the FDA for use as an aid in the absorption and dispersion of other injectable drugs. In this study, rHuPH20 will be co-administered with both Humalog and Humulin-R in order to determine if it improves the absorption of these insulins to more closely mimic the body's natural increase in insulin in response to a meal.

Read the detailed description

Participants received all 4 interventions in the same order.

Dose-finding visits were conducted to identify the appropriate dose of Humalog and Humulin-R. For each Humalog dose-finding visit, a total of 24 U of rHuPH20 was injected SC per unit of Humalog, corresponding to a mass concentration of 18.2 micrograms per milliliter (μg/mL) rHuPH20 (at final concentration of 91 U/mL of Humalog). For each Humulin-R dose-finding visit, a total of 24 U of rHuPH20 was injected SC per unit of Humulin-R, corresponding to a mass concentration of 20.0 μg/mL rHuPH20 (at final concentration of 100 U/mL of Humulin-R).

Conditions: Type 1 Diabetes Mellitus
Being tested: Humalog, Humulin-R, Recombinant human hyaluronidase PH20 (rHuPH20), Liquid meal
Keywords: Recombinant Hyaluronidase, Type 1 Diabetes Mellitus, Humalog, Humulin R, rHuPH20, Hylenex
Medical subject headings: Diabetes Mellitus, Type 1, Insulin Resistance

What participants receive

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

HumalogDrug
Also called Insulin lispro
Humulin-RDrug
Also called Humulin, Recombinant human insulin
Recombinant human hyaluronidase PH20 (rHuPH20)Drug
Also called HYLENEX, PH20
Liquid mealOther
Also called Ensure

Study groups in NCT00774800
Study group	Role	What they receive
First Humalog+PH20, then Humalog, Humulin-R+PH20, Humulin-R	Experimental	Humalog + Recombinant human hyaluronidase PH20 (rHuPH20) (Intervention 1): 24 units (U) of rHuPH20 per unit of Humalog, injected subcutaneously (SC), for up to 3 visits until an appropriate dose was identified. Humalog alone (Intervention 2): a single SC injection of the appropriate identified dose of Humalog, delivered before a liquid meal. Humulin-R + rHuPH20 (Intervention 3): 24 U of rHuPH20 per unit of Humulin-R, injected SC, for up to 2 visits until an appropriate dose was identified. Humulin-R alone (Intervention 4): a single SC injection of the appropriate identified dose of Humulin-R, delivered before a liquid meal. Appropriate dose of either Humalog or Humulin-R was that at which blood glucose following a liquid meal was <160 milligrams per deciliter (mg/dL) for more than 30 minutes during the first 4 hours after injection and never fell below 60 mg/dL. All dose finding visits and interventions were separated by 3-10 days. Receives: Drug: Humalog; Drug: Humulin-R; Drug: Recombinant human hyaluronidase PH20 (rHuPH20); Other: Liquid meal

What is being measured

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

Area Under the Insulin Concentration-time Curve for the First Hour (AUC0-60)
AUC was derived as the area under the serum insulin concentration profile from 0 to time "t." Samples were taken 30, 20, and 10 minutes (mins) prior to treatment; every 3 mins from mins 0 through 15; and at 20, 30, 45, and 60 mins postdose.
Measured: Predose up to 60 minutes postdose

Secondary outcomes (3)

Maximum Serum Insulin Concentration (Cmax)
Cmax was determined as the maximum of all valid serum insulin concentration measurements for each measurement series. Samples were taken 30, 20, and 10 minutes (mins) prior to treatment; every 3 mins from mins 0 through 15; at 20, 30, and 45 mins; every 30 mins from mins 60 through 240; and every 60 minutes from mins 300 through 480 postdose.
Measured: Predose up to 480 minutes postdose
Time to Maximum Serum Insulin Concentration (Tmax)
Tmax was determined as the timepoint where the maximum of all valid concentration measurements for each measurement series was observed. Samples were taken 30, 20, and 10 minutes (mins) prior to treatment; every 3 mins from mins 0 through 15; at 20, 30, and 45 mins; every 30 mins from mins 60 through 240; and every 60 minutes from mins 300 through 480 postdose.
Measured: Predose up to 480 minutes postdose
Area Under the Blood Glucose Time-Concentration Curve Blood Glucose (AUC[BG])
AUC(BG) values are reported for participants whose blood glucose (BG) was elevated higher than 140 milligrams per deciliter (mg/dL) within 4 hours of consuming a liquid meal. Blood samples were collected at 30, 20, 10, and within 5 minutes before; at 3, 6, 9, 12, 15, 20, 25 minutes; and every 10 minutes from minute 30 to 240 postdose.
Measured: Predose up to 4 hours after injection of study drug

Timeline

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

Oct 2008Mar 2009

First posted17 Oct 2008 (estimated)
Study startOct 2008
Primary completionMar 2009
Study completionMar 2009

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.
Publications (1)Papers the sponsor has linked to this study.
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 2
Primary purpose: Treatment
Intervention model: Crossover
Masking: Single blind
Who is masked: Participant
Enrolment: 22 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00774800
Sponsor's protocol ID: HZ2-08-05
Other IDs: HALO-117-201
Status last verified: Feb 2019
First submitted: 15 Oct 2008
Last updated: 26 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Hompesch M, Muchmore DB, Morrow L, Vaughn DE. Accelerated insulin pharmacokinetics and improved postprandial glycemic control in patients with type 1 diabetes after coadministration of prandial insulins with hyaluronidase. Diabetes Care. 2011 Mar;34(3):666-8. doi: 10.2337/dc10-1892. Epub 2011 Jan 27.
PubMed 21273493

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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All Type 1 Diabetes Mellitus trials

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: Phase II Study Evaluating Pharmacokinetics and Postprandial Glycemic Response of Subcutaneously Injected Humalog and Humulin R With/Without Co-Injected Recombinant Human Hyaluronidase Following Liquid Meal in Type1 Diabetes Mellitus Patients
ClinicalTrials.gov ID: NCT00774800
Acronym / sponsor ID: HZ2-08-05
Conditions: Type 1 Diabetes Mellitus
Keywords: Recombinant Hyaluronidase, Type 1 Diabetes Mellitus, Humalog, Humulin R, rHuPH20, Hylenex
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 22 participants (actual)
Lead sponsor: Halozyme TherapeuticsIndustry (pharma, biotech, devices)
Study start: Oct 2008
Primary completion: Mar 2009 (actual)
Study completion: Mar 2009 (actual)
First posted: 17 Oct 2008 (estimated)
Results: Posted 5 Sep 2014

Clinical summary

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

Detailed description

Participants received all 4 interventions in the same order.

Study design

Primary purpose: Treatment
Intervention model: Crossover
Masking: Single blind (participant)
Number of arms: 1

Arm	Type	Receives
First Humalog+PH20, then Humalog, Humulin-R+PH20, Humulin-R	Experimental	Drug: Humalog, Drug: Humulin-R, Drug: Recombinant human hyaluronidase PH20 (rHuPH20), Other: Liquid mealHumalog + Recombinant human hyaluronidase PH20 (rHuPH20) (Intervention 1): 24 units (U) of rHuPH20 per unit of Humalog, injected subcutaneously (SC), for up to 3 visits until an appropriate dose was identified. Humalog alone (Intervention 2): a single SC injection of the appropriate identified dose of Humalog, delivered before a liquid meal. Humulin-R + rHuPH20 (Intervention 3): 24 U of rHuPH20 per unit of Humulin-R, injected SC, for up to 2 visits until an appropriate dose was identified. Humulin-R alone (Intervention 4): a single SC injection of the appropriate identified dose of Humulin-R, delivered before a liquid meal. Appropriate dose of either Humalog or Humulin-R was that at which blood glucose following a liquid meal was <160 milligrams per deciliter (mg/dL) for more than 30 minutes during the first 4 hours after injection and never fell below 60 mg/dL. All dose finding visits and interventions were separated by 3-10 days.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Male or female 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.
Participants with Type 1 diabetes mellitus treated with insulin for greater than or equal to 12 months.
Body mass index (BMI) 18.0 to 29.0 kilograms per meter squared (kg/m^2), inclusive.
Glycosylated hemoglobin A1c (HbA1c) less than or equal to 10% based on local laboratory results.
Fasting C-peptide less than 0.6 nanograms per milliliter (ng/mL).

Key exclusion criteria (16 listed)

Known or suspected allergy to any component of any of the study drugs in this trial.
Previous enrollment in this trial.
A participant who has proliferative retinopathy or maculopathy, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.
Clinically significant (as judged by the Investigator) active disease of the gastrointestinal, cardiovascular (including a history of arrhythmia or conduction delays on electrocardiogram [ECG]), hepatic, neurological, renal, genitourinary, or hematological systems, or uncontrolled hypertension (diastolic blood pressure greater than or equal to 100 millimeters of mercury [mmHg] and/or systolic blood pressure greater than or equal to 160 mmHg after 5 minutes in the supine position).
History of any illness or disease that in the opinion of the Investigator might confound the results of the trial or pose additional risk in administering the study drugs to the participant.

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
HumalogAlso: Insulin lispro	Drug	First Humalog+PH20, then Humalog, Humulin-R+PH20, Humulin-R
Humulin-RAlso: Humulin, Recombinant human insulin	Drug	First Humalog+PH20, then Humalog, Humulin-R+PH20, Humulin-R
Recombinant human hyaluronidase PH20 (rHuPH20)Also: HYLENEX, PH20	Drug	First Humalog+PH20, then Humalog, Humulin-R+PH20, Humulin-R
Liquid mealAlso: Ensure	Other	First Humalog+PH20, then Humalog, Humulin-R+PH20, Humulin-R

Primary outcome

Area Under the Insulin Concentration-time Curve for the First Hour (AUC0-60)
Time frame: Predose up to 60 minutes postdose
AUC was derived as the area under the serum insulin concentration profile from 0 to time "t." Samples were taken 30, 20, and 10 minutes (mins) prior to treatment; every 3 mins from mins 0 through 15; and at 20, 30, 45, and 60 mins postdose.

3 secondary outcomes

Maximum Serum Insulin Concentration (Cmax)
Time frame: Predose up to 480 minutes postdose
Time to Maximum Serum Insulin Concentration (Tmax)
Time frame: Predose up to 480 minutes postdose
Area Under the Blood Glucose Time-Concentration Curve Blood Glucose (AUC[BG])
Time frame: Predose up to 4 hours after injection of study drug

Results and safety

Results posted to the registry on 5 Sep 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
First Humalog+PH20, Then Humalog, Humulin-R+PH20, Humulin-R	22	22

Primary outcome: Area Under the Insulin Concentration-time Curve for the First Hour (AUC0-60)

Time frame: Predose up to 60 minutes postdose. Mean (Standard Deviation). Unit: nanomole*minute per liter (nmol*min/L)

Measure	Humalog + rHuPH20 n = 21	Humalog Alone n = 21	Humulin-R + rHuPH20 n = 17	Humulin-R Alone n = 17
Value	12346.67 (4996.79)	8297.62 (3670.03)	11607.65 (6770.61)	4331.76 (3068.10)

Humalog + rHuPH20 vs Humalog Alone: Geometric Least Squares Means Ratio: 1.54, p = 0.0011, ANOVA
Humulin-R + rHuPH20 vs Humulin-R Alone: Geometric Least Squares Means Ratio: 3.06, p <0.0001, ANOVA

Population analysed: Participants who received at least one dose of Humalog alone, Humalog + rHuPH20, Humulin-R + rHuPH20, or Humulin-R alone with evaluable AUC0-60 data.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data collected from Day 1 through to the end of the study, for up to 80 days.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Humalog + rHuPH20	0 of 22 (0%)	14 of 22 (63.6%)	Not reported
Humalog Alone	0 of 22 (0%)	15 of 22 (68.2%)	Not reported
Humulin-R + rHuPH20	0 of 22 (0%)	18 of 22 (81.8%)	Not reported
Humulin-R Alone	0 of 21 (0%)	18 of 21 (85.7%)	Not reported

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.
Results publication: PubMed 21273493Hompesch M, Muchmore DB, Morrow L, Vaughn DE. Accelerated insulin pharmacokinetics and improved postprandial glycemic control in patients with type 1 diabetes after coadministration of prandial insulins with hyaluronidase. Diabetes Care. 2011 Mar;34(3):666-8. doi: 10.2337/dc10-1892. Epub 2011 Jan 27.

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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 A Morrow, M.D. 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 2 study testing Humalog, Humulin-R 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 7 inclusion and 16 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 5 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?

Area Under the Insulin Concentration-time Curve for the First Hour (AUC0-60) (time frame: Predose up to 60 minutes postdose). 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 NCT00774800, which also lists 1 linked publication.

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.