Diabetes MellitusPhase 1NCT00862849

Pharmacokinetic and Glucodynamic Crossover Study of Subcutaneously (SC) Administered Insulin Lispro + Recombinant Human Hyaluronidase (rHuPH20) and Regular Human Insulin + rHuPH20 Compared to Insulin Lispro Alone

A Phase 1 study testing Insulin Lispro, Regular Human Insulin and rHuPH20 in people with 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 55 yearsHealthy volunteers can take part
Conditions the study is for: Diabetes Mellitus
What is being tested?: Insulin Lispro, Regular Human Insulin and 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: Mar 2009to Aug 2009
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 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy participants between the ages of 18 and 55 years, inclusive. (Healthy is defined as no clinically relevant abnormalities.)
Body mass index (BMI) between 18-27 kilograms per meter squared (kg/m^2), inclusive.
Total body weight >65 kilograms (kg) (143 pounds [lb]) for men and >46 kg (101 lb) for women.
Decision making capacity and willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including adequate venous access.
Vital signs (blood pressure, pulse rate, body temperature) within normal range or, if out of range, assessed by the Principal Investigator (PI) as not clinically significant (NCS).
Fasting blood glucose level <100 milligrams per deciliter (mg/dL) at screening.

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A negative serum pregnancy test (if female of childbearing potential).
Female participants of childbearing potential must agree to be practicing effective birth control or abstinence currently and agree to continue to do so for the duration of their time on study.
Signed, written Institutional Review Board (IRB)-approved informed consent.

Who cannot join

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, oncologic, or neurologic (to include history of seizures) disease; hypoglycemic episodes; intercurrent illness (such as influenza); or allergic disease (including severe drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Clinical significance to be determined by the PI.
As judged by the Investigator, clinically significant findings in routine laboratory data. (Anemia with hematocrit less than 33% at screening is specifically exclusionary.)
Known history of diabetes mellitus (type 1 or type 2) or gestational diabetes.
Known allergy to hyaluronidase or any other ingredient in the study drug.
Positive human immunodeficiency virus (HIV 1) antibody test, hepatitis B (anti-hepatitis B surface antigen [anti-HBsAg]) or hepatitis C (anti-hepatitis C virus [anti-HCV]) antibody test.
History or evidence of alcohol or drug abuse.

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History or evidence of use of any tobacco or nicotine-containing product within 6 months of screening and a screening qualitative urine nicotine test.
Use of drugs that may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action or glucose utilization.
Donation of blood in excess of 500 milliliters (mL) within 56 days before dosing.
Participation in a study of any investigational drug or device 30 days before enrollment in this study.
The participant is unfit for the study in the opinion of the Investigator.
Women who are pregnant or breast-feeding.

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 1, Randomized, Double-Blind, Pharmacokinetic and Glucodynamic 6-Way Crossover Study of SC Administered Insulin Lispro With Recombinant Human Hyaluronidase (rHuPH20) and Regular Human Insulin With Recombinant Human Hyaluronidase (rHuPH20) Compared to Insulin Lispro Alone in Healthy Volunteers

Insulin lispro and regular human insulin are Food and Drug Administration (FDA)-approved medications for the treatment of diabetes mellitus. Recombinant human hyaluronidase (rHuPH20) is approved by the FDA as an aid to the absorption and dispersion of other injectable drugs. In this study, rHuPH20 will be co-administered with both insulin lispro and regular human insulin 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

The purpose of this study is to compare the pharmacokinetics (absorption, distribution, breakdown and elimination) of regular human insulin + recombinant human hyaluronidase (rHuPH20) versus insulin lispro alone, and to compare the pharmacokinetics of insulin lispro + rHuPH20 versus insulin lispro alone. The effects of regular human insulin + rHuPH20, insulin lispro + rHuPH20, and insulin lispro alone on the body will be evaluated by blood glucose measurements and by calculating the rate at which a glucose solution is infused to maintain blood glucose within a certain range. The safety and tolerability of insulin lispro with and without rHuPH20 and regular human insulin with rHuPH20 will be studied. The study drugs will be administered by subcutaneous (under the skin) injection.

Conditions: Diabetes Mellitus
Being tested: Insulin Lispro, Regular Human Insulin, rHuPH20
Keywords: rHuPH20, Recombinant Human Hyaluronidase, Insulin Lispro, Regular Human Insulin
Medical subject headings: Diabetes Mellitus, Insulin Resistance

What participants receive

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

Insulin LisproDrug
Also called Humalog
Regular Human InsulinDrug
Also called RHI, Humulin R
rHuPH20Drug
Also called recombinant human hyaluronidase, HYLENEX

Study groups in NCT00862849
Study group	Role	What they receive
Insulin Lispro, Regular Human Insulin, rHuPH20	Experimental	All participants were randomized to 1 of 6 treatment sequences (ABC, ACB, BAC, BCA, CAB, or CBA), each of which was comprised of the same 3 interventions (A, B, and C). Intervention A: a single, subcutaneous (SC) injection of 0.15 units per kilogram (U/kg) insulin lispro with 3.75 nanograms per kilogram (ng/kg) recombinant human hyaluronidase (rHuPH20) Intervention B: a single, SC injection of 0.15 U/kg regular human insulin (RHI) with 3.75 ng/kg rHuPH20 Intervention C: a single, SC injection of 0.15 U/kg insulin lispro alone There was a washout period of 3 to 14 days between interventions. The treatment sequence (ABC, ACB, BAC, BCA, CAB, or CBA) was repeated once so that each participant received up to 6 injections. Receives: Drug: Insulin Lispro; Drug: Regular Human Insulin; Drug: rHuPH20

What is being measured

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

Intra-participant Variability in Percent of Total Area Under the Plasma Insulin Concentration-Versus-Time Curve Attained by Time T (%AUC[0-T])
Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); and every 5 mins (from 15 to 30 mins) after each injection. The percent coefficient of variation (CV%) was calculated as 100*(standard deviation/mean). The intra-participant CV% was calculated directly from the 2 replications of each treatment. The CV% for percentage of total AUC is reported from 0 to 30 minutes.
Measured: predose up to 30 minutes postdose

Secondary outcomes (5)

Time to Early and Late 50% Maximum Serum Insulin Concentration (t[50%Max])
Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); every 30 mins (from 90 to 240 mins); and every 60 mins (from 240 to 480 mins) after each injection.
Measured: predose up to 480 minutes postdose
Peak Serum Insulin Concentration (Cmax)
Cmax was determined as the maximum of all valid serum insulin concentration measurements for each measurement series. Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); every 30 mins (from 90 to 240 mins); and every 60 mins (from 240 to 480 mins) after each injection.
Measured: predose up to 480 minutes postdose
Time to Percentage of Total Glucose Infused
Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); every 30 mins (from 90 to 240 mins); and every 60 mins (from 240 to 480 mins) after each injection. Time to 25%, 50%, and 75% of total glucose infused are summarized.
Measured: predose up to 480 minutes postdose
Percentage of Total Glucose Infused
Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); every 5 mins (from 15 to 30 mins); every 15 mins (from 30 to 90 mins); and every 30 mins (from 90 to 240 mins) after each injection. Percentage of total glucose infused from 0 to 4 hours is summarized.
Measured: predose up to 240 minutes postdose
Number of Treatment Emergent Adverse Events (TEAEs) Related to Study Drug
The number of TEAEs related to study drug (as determined by the Investigator) are summarized. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Measured: first dose through 7 to 10 days after last dose

Timeline

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

Mar 2009Aug 2009

First posted17 Mar 2009 (estimated)
Study startMar 2009
Primary completionJun 2009
Study completionAug 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 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
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 22 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00862849
Sponsor's protocol ID: HALO-117-103
Status last verified: Jul 2014
First submitted: 13 Mar 2009
Last updated: 22 Jul 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Morrow L, Muchmore DB, Ludington EA, Vaughn DE, Hompesch M. Reduction in intrasubject variability in the pharmacokinetic response to insulin after subcutaneous co-administration with recombinant human hyaluronidase in healthy volunteers. Diabetes Technol Ther. 2011 Oct;13(10):1039-45. doi: 10.1089/dia.2011.0115. Epub 2011 Jun 29.
PubMed 21714645

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 22 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1, Randomized, Double-Blind, Pharmacokinetic and Glucodynamic 6-Way Crossover Study of SC Administered Insulin Lispro With Recombinant Human Hyaluronidase (rHuPH20) and Regular Human Insulin With Recombinant Human Hyaluronidase (rHuPH20) Compared to Insulin Lispro Alone in Healthy Volunteers
ClinicalTrials.gov ID: NCT00862849
Acronym / sponsor ID: HALO-117-103
Conditions: Diabetes Mellitus
Keywords: rHuPH20, Recombinant Human Hyaluronidase, Insulin Lispro, Regular Human Insulin
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 22 participants (actual)
Lead sponsor: Halozyme TherapeuticsIndustry (pharma, biotech, devices)
Study start: Mar 2009
Primary completion: Jun 2009 (actual)
Study completion: Aug 2009 (actual)
First posted: 17 Mar 2009 (estimated)
Results: Posted 11 Jul 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

Study design

Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 1

Arm	Type	Receives
Insulin Lispro, Regular Human Insulin, rHuPH20	Experimental	Drug: Insulin Lispro, Drug: Regular Human Insulin, Drug: rHuPH20All participants were randomized to 1 of 6 treatment sequences (ABC, ACB, BAC, BCA, CAB, or CBA), each of which was comprised of the same 3 interventions (A, B, and C). Intervention A: a single, subcutaneous (SC) injection of 0.15 units per kilogram (U/kg) insulin lispro with 3.75 nanograms per kilogram (ng/kg) recombinant human hyaluronidase (rHuPH20) Intervention B: a single, SC injection of 0.15 U/kg regular human insulin (RHI) with 3.75 ng/kg rHuPH20 Intervention C: a single, SC injection of 0.15 U/kg insulin lispro alone There was a washout period of 3 to 14 days between interventions. The treatment sequence (ABC, ACB, BAC, BCA, CAB, or CBA) was repeated once so that each participant received up to 6 injections.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (9 listed)

Healthy participants between the ages of 18 and 55 years, inclusive. (Healthy is defined as no clinically relevant abnormalities.)
Body mass index (BMI) between 18-27 kilograms per meter squared (kg/m^2), inclusive.
Total body weight >65 kilograms (kg) (143 pounds [lb]) for men and >46 kg (101 lb) for women.
Decision making capacity and willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including adequate venous access.
Vital signs (blood pressure, pulse rate, body temperature) within normal range or, if out of range, assessed by the Principal Investigator (PI) as not clinically significant (NCS).

Key exclusion criteria (12 listed)

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, oncologic, or neurologic (to include history of seizures) disease; hypoglycemic episodes; intercurrent illness (such as influenza); or allergic disease (including severe drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Clinical significance to be determined by the PI.
As judged by the Investigator, clinically significant findings in routine laboratory data. (Anemia with hematocrit less than 33% at screening is specifically exclusionary.)
Known history of diabetes mellitus (type 1 or type 2) or gestational diabetes.
Known allergy to hyaluronidase or any other ingredient in the study drug.
Positive human immunodeficiency virus (HIV 1) antibody test, hepatitis B (anti-hepatitis B surface antigen [anti-HBsAg]) or hepatitis C (anti-hepatitis C virus [anti-HCV]) antibody test.

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 LisproAlso: Humalog	Drug	Insulin Lispro, Regular Human Insulin, rHuPH20
Regular Human InsulinAlso: RHI, Humulin R	Drug	Insulin Lispro, Regular Human Insulin, rHuPH20
rHuPH20Also: recombinant human hyaluronidase, HYLENEX	Drug	Insulin Lispro, Regular Human Insulin, rHuPH20

Primary outcome

Intra-participant Variability in Percent of Total Area Under the Plasma Insulin Concentration-Versus-Time Curve Attained by Time T (%AUC[0-T])
Time frame: predose up to 30 minutes postdose
Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); and every 5 mins (from 15 to 30 mins) after each injection. The percent coefficient of variation (CV%) was calculated as 100*(standard deviation/mean). The intra-participant CV% was calculated directly from the 2 replications of each treatment. The CV% for percentage of total AUC is reported from 0 to 30 minutes.

5 secondary outcomes

Time to Early and Late 50% Maximum Serum Insulin Concentration (t[50%Max])
Time frame: predose up to 480 minutes postdose
Peak Serum Insulin Concentration (Cmax)
Time frame: predose up to 480 minutes postdose
Time to Percentage of Total Glucose Infused
Time frame: predose up to 480 minutes postdose
Percentage of Total Glucose Infused
Time frame: predose up to 240 minutes postdose
Number of Treatment Emergent Adverse Events (TEAEs) Related to Study Drug
Time frame: first dose through 7 to 10 days after last dose

Results and safety

Results posted to the registry on 11 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
Lispro+rHuPH20 First, Then RHI+rHuPH20, Then Lispro Alone	3	3
Lispro+rHuPH20 First, Then Lispro Alone, Then RHI+rHuPH20	5	5
RHI+rHuPH20 First, Then Lispro+rHuPH20, Then Lispro Alone	3	3
RHI+rHuPH20 First, Then Lispro Alone, Then Lispro+rHuPH20	4	4
Lispro Alone First, Then Lispro+rHuPH20, Then RHI+rHuPH20	4	4
Lispro Alone First, Then RHI+rHuPH20, Then Lispro+rHuPH20	3	3

Primary outcome: Intra-participant Variability in Percent of Total Area Under the Plasma Insulin Concentration-Versus-Time Curve Attained by Time T (%AUC[0-T])

Time frame: predose up to 30 minutes postdose. Mean (Standard Deviation). Unit: percentage of coefficient of variance

Measure	Insulin Lispro + rHuPH20 n = 20	Regular Human Insulin + rHuPH20 n = 20	Insulin Lispro Alone n = 20
Value	14.04 (11.12)	23.81 (12.43)	40.51 (24.30)

Insulin Lispro + rHuPH20 vs Insulin Lispro Alone: LS Mean Difference: 26.47 (90% CI 18.22 to 34.71), p <0.0001, Mixed Models Analysis
Regular Human Insulin + rHuPH20 vs Insulin Lispro Alone: LS Mean Difference: 16.70 (90% CI 8.45 to 24.94), p = 0.0015, Mixed Models Analysis

Population analysed: Participants who completed all study visits and had evaluable %AUC(0-t) data.

5 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
Insulin Lispro + rHuPH20	0 of 22 (0%)	4 of 22 (18.2%)	Not reported
Regular Human Insulin + rHuPH20	0 of 20 (0%)	4 of 20 (20%)	Not reported
Insulin Lispro Alone	0 of 21 (0%)	9 of 21 (42.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21714645Morrow L, Muchmore DB, Ludington EA, Vaughn DE, Hompesch M. Reduction in intrasubject variability in the pharmacokinetic response to insulin after subcutaneous co-administration with recombinant human hyaluronidase in healthy volunteers. Diabetes Technol Ther. 2011 Oct;13(10):1039-45. doi: 10.1089/dia.2011.0115. Epub 2011 Jun 29.

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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 1 study testing Insulin Lispro, Regular Human Insulin and rHuPH20 in people with 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 12 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 22 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 11 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?

Intra-participant Variability in Percent of Total Area Under the Plasma Insulin Concentration-Versus-Time Curve Attained by Time T (%AUC[0-T]) (time frame: predose up to 30 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 NCT00862849, 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 22 Jul 2014.