Diabetes MellitusPhase 1NCT00705536

Pharmacokinetic (PK), Pharmacodynamic (PD), and Safety Study of Subcutaneously Administered Humalog® With and Without Recombinant Human Hyaluronidase (rHuPH20)and Humulin-R® With and Without rHuPH20

A Phase 1 study testing Humalog, Humulin-R and Recombinant human hyaluronidase PH20 (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

The purpose of the study is to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of Humalog (insulin lispro) or Humulin-R (recombinant human insulin) when administered as a single subcutaneous (SC) injection of 20 units (U) with or without coadministration of recombinant human hyaluronidase PH20 (rHuPH20). Read more about this study

Who is it for?: Ages 18 to 55 years, men onlyHealthy volunteers can take part
Conditions the study is for: 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: 26 participants
Where: 1 siteUnited States
Study dates: Dec 2007to Feb 2008
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
Men only
Healthy volunteers accepted
Adult

Who may be able to join

Healthy male participants aged 18 to 55 years.
Body mass index (BMI) 18 to 28 kilograms per meter squared (kg/m^2) and total body weight >70 kilograms (kg) (154 pounds [lb]).
Willingness and ability to comply with the protocol.
Vital signs within the normal range.
Within 7 days before the first injection, metabolic panel results and complete blood count (CBC) within the laboratory normal reference range.
Fasting plasma glucose within the normal range of 90 to 110 milligrams per deciliter (mg/dL) on the morning of the glucose clamp.
Agreement not to father a child or donate sperm and to use effective contraception during the study and for at least 30 days after study completion.
Willingness and ability to sign an informed consent form.

Who cannot join

Evidence or history of clinically significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic (to include history of seizures) or allergic disease, or history of hypoglycemic episodes.
Known history of diabetes mellitus.
Prior exposure to any insulin or insulin analogs.
Known allergy to hyaluronidase or any other ingredient in HYLENEX.
Known allergy to bee or vespid venom.
Positive urine drug screen results.

Show all 15Show fewer

Positive human immunodeficiency virus (HIV) 1, HIV 2, hepatitis B, or hepatitis C antibody test result.
Any history or evidence of alcohol or drug abuse.
History or evidence of use of any tobacco- or nicotine-containing product within 6 months of screening, or screening urine nicotine concentration >50 nanograms per milliliter (ng/mL).
Use of prescription or nonprescription drugs within 7 days or 5 half-lives, whichever was shorter, except acetaminophen at doses of less than or equal to 1 gram per day (g/day).
Donation of blood in excess of 500 milliliters (mL) within 56 days before dosing.
Failure to limit alcohol consumption and refrain from exercise within 48 hours before each injection.
Known clinically significant intercurrent illness or other major systemic disease that would unduly risk the participant's safety or interfere with the interpretation of results.
Participation in a study of any investigational drug or device 30 days before enrollment in this study.
Unfitness for the study, in the investigator's opinion.

Trial locations and contacts

1 site in 1 country.

United States1 site

Diabetes and Glandular Disease Research, Inc.
San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: A Phase I, Randomized, Double-Blind Crossover Pharmacokinetic, Pharmacodynamic, and Safety Study of Subcutaneously Administered Humalog® (Insulin Lispro Injection; Rapid-Acting Insulin) With and Without Recombinant Human Hyaluronidase (rHuPH20) Versus Subcutaneously Administered Humulin R® (Regular Insulin Injection) With and Without rHuPH20

The study hypothesizes that the time required to reach maximum insulin concentration (tmax) when insulin is administered with rHuPH20 will be comparable or shorter than the time required without rHuPH20.

Conditions: Diabetes Mellitus
Being tested: Humalog, Humulin-R, Recombinant human hyaluronidase PH20 (rHuPH20)
Keywords: rHuPH20, Hyaluronidase, 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.

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

Study groups in NCT00705536
Study group	Role	What they receive
Humalog first, then Humalog + rHuPH20	Active comparator	Humalog first, then Humalog + recombinant human hyaluronidase PH20 (rHuPH20) A single subcutaneous (SC) injection of 20 units (U) Humalog on Day 1 of the study, followed by a single SC injection of 20 U Humalog + 300 U rHuPH20 after a washout period of at least 6 days Receives: Drug: Humalog; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Humalog + rHuPH20 first, then Humalog	Active comparator	Humalog + recombinant human hyaluronidase PH20 (rHuPH20) first, then Humalog A single subcutaneous (SC) injection of 20 units (U) Humalog + 300 U rHuPH20 on Day 1 of the study, followed by a single SC injection of 20 U Humalog after a washout period of at least 6 days Receives: Drug: Humalog; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Humulin-R first, then Humulin-R + rHuPH20	Active comparator	Humulin-R (recombinant human insulin) first, then Humulin-R + recombinant human hyaluronidase PH20 (rHuPH20) A single subcutaneous (SC) injection of 20 units (U) Humulin-R on Day 1 of the study, followed by a single SC injection of 20 U Humulin-R + 240 U rHuPH20 after a washout period of at least 6 days Receives: Drug: Humulin-R; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
Humulin-R + rHuPH20 first, then Humulin-R	Active comparator	Humulin-R (recombinant human insulin) + recombinant human hyaluronidase PH20 (rHuPH20) first, then Humulin-R A single subcutaneous (SC) injection of 20 units (U) Humulin-R + 240 U rHuPH20 on Day 1 of the study, followed by a single SC injection of 20 U Humulin-R after a washout period of at least 6 days Receives: Drug: Humulin-R; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)

What is being measured

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

Time to Maximum Serum Insulin Concentration (Tmax)
Time to maximum serum insulin concentration (tmax) values for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from 3 milliliter (mL) blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Measured: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Maximum Serum Insulin Concentration (Cmax)
Maximum serum insulin concentration (Cmax) values for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from 3 milliliter (mL) blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Measured: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Area Under the Serum Concentration-Time Curve From Time Zero to the Time Required to Reach Endogenous Plasma Glucose Levels (AUC[0-t'])
Area under the serum concentration-time curve from time zero to the time required to reach endogenous plasma glucose levels (AUC[0-t']) for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from 3 milliliter (mL) blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Measured: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Area Under the Concentration-Time Curve From Time 0 to Time to Reach Maximum Concentration (Tmax) for Serum Insulin With Recombinant Human Hyaluronidase PH20 (rHuPH20) (AUC[0-tmaxPH20])
Area under the concentration-time curve from time 0 to time to reach maximum concentration (tmax) for serum insulin (Humalog or Humulin-R) with recombinant human hyaluronidase (rHuPH20) (AUC[0-tmaxPH20]) for participants who received Humalog or Humulin-R and with rHuPH20 were measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment and every 3 min from min 0 through 48 for Stage 1 and, and every 3 min from min 0 through 68 for Stage 2 during the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Measured: Predose and up to 48 minutes postdose during Stage 1, or up to 68 minutes postdose during Stage 2
Relative Bioavailability (Area Under the Curve [AUC] for Insulin + Recombinant Human Hyaluronidase [rHuPH20] / AUC for Insulin Alone)
Relative bioavailability was determined by dividing the baseline-corrected geometric mean of the area under the curve (AUC) for insulin (ins) (Humalog or Humulin-R) with recombinant human hyaluronidase PH20 (rHuPH20) by the baseline-corrected geometric mean of the AUC for insulin alone (AUC[insulin+rHuPH20]/AUC[insulin]).
Bioavailability values for participants who received Humalog or Humulin-R and rHuPH20 were measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Measured: Predose and up to 360 minutes postdose during Stage 1 or Stage 2

Secondary outcomes (9)

Time to Maximum Glucose Infusion Rate (tGIR[Max])
Time to maximal effect for glucose infusion rate (tGIR[max]) for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from blood samples obtained every 3 minutes during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Measured: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Time to Early Half-Maximal Effect for Glucose Infusion Rate (tGIR[early50%])
Time to early half-maximal effect for glucose infusion rate (tGIR[early50%]) for participants who were randomized to Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Measured: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Time to Late Half-Maximal Effect for Glucose Infusion Rate (tGIR[late50%])
Time to late half-maximal effect for glucose infusion rate (tGIR[late50%]) for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase (rHuPH20) were measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Because the study was only 360 minutes in duration, there was not sufficient time for regular human insulin to show an effect and therefore tGIR(late50%) could not be calculated for participants receiving Humulin-R alone.
Measured: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Maximum Glucose Infusion Rate (GIR[Max])
Maximum glucose infusion rate (GIR[max]) for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Measured: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Area Under the Glucose Infusion Rate Curve From 0 to 60 Minutes After Injection (AUC[GIR{0-60}])
The area under the curve for the glucose infusion rate from minutes (min) 0 to 60 after injection (AUC[GIR{0-60}]) for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase (rHuPH20) was measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 min prior to treatment and every 3 min from min 0 through 60 during the clamp procedure. Means were calculated using analysis of variance with fixed of participant, sequence within participant, treatment, and period.
Measured: Predose and up to 60 minutes postdose during Stage 1 or Stage 2
Area Under the Glucose Infusion Rate Curve From 0 to 120 Minutes After Injection (AUC[GIR{0-120}])
The area under the glucose infusion rate curve from minutes 0 to 120 after injection (AUC[GIR{0-120}]) for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase (rHuPH20) was measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, and every 15 min from min 60 through 120 during the clamp. Means were calculated using analysis of variance with fixed effects of participant, sequence within participant, treatment, and period.
Measured: Predose and up to 120 minutes postdose during Stage 1 or Stage 2
Area Under the Glucose Infusion Rate Curve From 0 to 180 Minutes After Injection (AUC[GIR{0-180}])
The area under the curve for the glucose infusion rate from minutes (min) 0 to 180 after injection (AUC[GIR{0-180}]) for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase (rHuPH20) was measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 min prior to treatment, every 3 min from min 0 through 60, and every 15 min from min 60 through 180 during the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Measured: Predose and up to 180 minutes postdose during Stage 1 or Stage 2
Area Under the Glucose Infusion Rate Curve From 0 to 240 Minutes After Injection (AUC[GIR{0-240}])
The area the glucose infusion rate curve from minutes (min) 0 to 240 after injection (AUC[GIR{0-240}]) for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase (rHuPH20) was measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 min prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 to 240 during the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Measured: Predose up to 240 minutes postdose during Stage 1 or Stage 2
Area Under the Glucose Infusion Rate Curve From 0 to 360 Minutes After Injection (AUC[GIR{0-360}])
The area under glucose infusion rate curve from minutes (min) 0 to 360 after injection (AUC[GIR{0-360}]) for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase (rHuPH20) was measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 min prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 to 360 during the clamp. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Measured: Predose and up to 360 minutes postdose during Stage 1 or Stage 2

Timeline

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

Dec 2007Feb 2008

First posted26 Jun 2008 (estimated)
Study startDec 2007
Primary completionFeb 2008
Study completionFeb 2008

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
Primary purpose: Health services research
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00705536
Sponsor's protocol ID: HZ2-07-04
Status last verified: Feb 2019
First submitted: 24 Jun 2008
Last updated: 26 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Vaughn DE, Yocum RC, Muchmore DB, Sugarman BJ, Vick AM, Bilinsky IP, Frost GI. Accelerated pharmacokinetics and glucodynamics of prandial insulins injected with recombinant human hyaluronidase. Diabetes Technol Ther. 2009 Jun;11(6):345-52. doi: 10.1089/dia.2009.0013.
PubMed 19459762

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 26 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Randomized, Double-Blind Crossover Pharmacokinetic, Pharmacodynamic, and Safety Study of Subcutaneously Administered Humalog® (Insulin Lispro Injection; Rapid-Acting Insulin) With and Without Recombinant Human Hyaluronidase (rHuPH20) Versus Subcutaneously Administered Humulin R® (Regular Insulin Injection) With and Without rHuPH20
ClinicalTrials.gov ID: NCT00705536
Acronym / sponsor ID: HZ2-07-04
Conditions: Diabetes Mellitus
Keywords: rHuPH20, Hyaluronidase, Insulin
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: Halozyme TherapeuticsIndustry (pharma, biotech, devices)
Study start: Dec 2007
Primary completion: Feb 2008 (actual)
Study completion: Feb 2008 (actual)
First posted: 26 Jun 2008 (estimated)
Results: Posted 14 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: Health services research
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Humalog first, then Humalog + rHuPH20	Active comparator	Drug: Humalog, Drug: Recombinant human hyaluronidase PH20 (rHuPH20)Humalog first, then Humalog + recombinant human hyaluronidase PH20 (rHuPH20) A single subcutaneous (SC) injection of 20 units (U) Humalog on Day 1 of the study, followed by a single SC injection of 20 U Humalog + 300 U rHuPH20 after a washout period of at least 6 days
Humalog + rHuPH20 first, then Humalog	Active comparator	Drug: Humalog, Drug: Recombinant human hyaluronidase PH20 (rHuPH20)Humalog + recombinant human hyaluronidase PH20 (rHuPH20) first, then Humalog A single subcutaneous (SC) injection of 20 units (U) Humalog + 300 U rHuPH20 on Day 1 of the study, followed by a single SC injection of 20 U Humalog after a washout period of at least 6 days
Humulin-R first, then Humulin-R + rHuPH20	Active comparator	Drug: Humulin-R, Drug: Recombinant human hyaluronidase PH20 (rHuPH20)Humulin-R (recombinant human insulin) first, then Humulin-R + recombinant human hyaluronidase PH20 (rHuPH20) A single subcutaneous (SC) injection of 20 units (U) Humulin-R on Day 1 of the study, followed by a single SC injection of 20 U Humulin-R + 240 U rHuPH20 after a washout period of at least 6 days
Humulin-R + rHuPH20 first, then Humulin-R	Active comparator	Drug: Humulin-R, Drug: Recombinant human hyaluronidase PH20 (rHuPH20)Humulin-R (recombinant human insulin) + recombinant human hyaluronidase PH20 (rHuPH20) first, then Humulin-R A single subcutaneous (SC) injection of 20 units (U) Humulin-R + 240 U rHuPH20 on Day 1 of the study, followed by a single SC injection of 20 U Humulin-R after a washout period of at least 6 days

Who may qualify

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

Key inclusion criteria (8 listed)

Healthy male participants aged 18 to 55 years.
Body mass index (BMI) 18 to 28 kilograms per meter squared (kg/m^2) and total body weight >70 kilograms (kg) (154 pounds [lb]).
Willingness and ability to comply with the protocol.
Vital signs within the normal range.
Within 7 days before the first injection, metabolic panel results and complete blood count (CBC) within the laboratory normal reference range.

Key exclusion criteria (15 listed)

Evidence or history of clinically significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic (to include history of seizures) or allergic disease, or history of hypoglycemic episodes.
Known history of diabetes mellitus.
Prior exposure to any insulin or insulin analogs.
Known allergy to hyaluronidase or any other ingredient in HYLENEX.
Known allergy to bee or vespid venom.

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	Humalog + rHuPH20 first, then Humalog, Humalog first, then Humalog + rHuPH20
Humulin-RAlso: Humulin, Recombinant human insulin	Drug	Humulin-R + rHuPH20 first, then Humulin-R, Humulin-R first, then Humulin-R + rHuPH20
Recombinant human hyaluronidase PH20 (rHuPH20)Also: PH20, HYLENEX	Drug	Humalog + rHuPH20 first, then Humalog, Humalog first, then Humalog + rHuPH20, Humulin-R + rHuPH20 first, then Humulin-R, Humulin-R first, then Humulin-R + rHuPH20

Primary outcome

Time to Maximum Serum Insulin Concentration (Tmax)
Time frame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Time to maximum serum insulin concentration (tmax) values for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from 3 milliliter (mL) blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Maximum Serum Insulin Concentration (Cmax)
Time frame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Maximum serum insulin concentration (Cmax) values for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from 3 milliliter (mL) blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Area Under the Serum Concentration-Time Curve From Time Zero to the Time Required to Reach Endogenous Plasma Glucose Levels (AUC[0-t'])
Time frame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Area under the serum concentration-time curve from time zero to the time required to reach endogenous plasma glucose levels (AUC[0-t']) for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from 3 milliliter (mL) blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Area Under the Concentration-Time Curve From Time 0 to Time to Reach Maximum Concentration (Tmax) for Serum Insulin With Recombinant Human Hyaluronidase PH20 (rHuPH20) (AUC[0-tmaxPH20])
Time frame: Predose and up to 48 minutes postdose during Stage 1, or up to 68 minutes postdose during Stage 2
Area under the concentration-time curve from time 0 to time to reach maximum concentration (tmax) for serum insulin (Humalog or Humulin-R) with recombinant human hyaluronidase (rHuPH20) (AUC[0-tmaxPH20]) for participants who received Humalog or Humulin-R and with rHuPH20 were measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment and every 3 min from min 0 through 48 for Stage 1 and, and every 3 min from min 0 through 68 for Stage 2 during the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Relative Bioavailability (Area Under the Curve [AUC] for Insulin + Recombinant Human Hyaluronidase [rHuPH20] / AUC for Insulin Alone)
Time frame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Relative bioavailability was determined by dividing the baseline-corrected geometric mean of the area under the curve (AUC) for insulin (ins) (Humalog or Humulin-R) with recombinant human hyaluronidase PH20 (rHuPH20) by the baseline-corrected geometric mean of the AUC for insulin alone (AUC[insulin+rHuPH20]/AUC[insulin]). Bioavailability values for participants who received Humalog or Humulin-R and rHuPH20 were measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.

9 secondary outcomes

Time to Maximum Glucose Infusion Rate (tGIR[Max])
Time frame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Time to Early Half-Maximal Effect for Glucose Infusion Rate (tGIR[early50%])
Time frame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Time to Late Half-Maximal Effect for Glucose Infusion Rate (tGIR[late50%])
Time frame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Maximum Glucose Infusion Rate (GIR[Max])
Time frame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2
Area Under the Glucose Infusion Rate Curve From 0 to 60 Minutes After Injection (AUC[GIR{0-60}])
Time frame: Predose and up to 60 minutes postdose during Stage 1 or Stage 2
Area Under the Glucose Infusion Rate Curve From 0 to 120 Minutes After Injection (AUC[GIR{0-120}])
Time frame: Predose and up to 120 minutes postdose during Stage 1 or Stage 2
Area Under the Glucose Infusion Rate Curve From 0 to 180 Minutes After Injection (AUC[GIR{0-180}])
Time frame: Predose and up to 180 minutes postdose during Stage 1 or Stage 2
Area Under the Glucose Infusion Rate Curve From 0 to 240 Minutes After Injection (AUC[GIR{0-240}])
Time frame: Predose up to 240 minutes postdose during Stage 1 or Stage 2
Area Under the Glucose Infusion Rate Curve From 0 to 360 Minutes After Injection (AUC[GIR{0-360}])
Time frame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2

Results and safety

Results posted to the registry on 14 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: Humalog First, Then Humalog + rHuPH20	6	6
Stage 1: Humalog + rHuPH20 First, Then Humalog	6	6
Stage 2: Humulin-R First, Then Humulin-R + rHuPH20	7	7
Stage 2: Humulin-R + rHuPH20 First, Then Humulin-R	7	6

Primary outcome: Time to Maximum Serum Insulin Concentration (Tmax)

Time frame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2. Mean (Standard Deviation). Unit: Minutes

Measure	Stage 1: Humalog Alone n = 12	Stage 1: Humalog + rHuPH20 n = 12	Stage 2: Humulin-R Alone n = 13	Stage 2: Humulin-R + rHuPH20 n = 13
Value	97.5 (35.9)	48.0 (7.99)	163 (51.5)	67.8 (19.1)

Stage 1: Humalog Alone vs Stage 1: Humalog + rHuPH20: p = 0.0006, ANOVA
Stage 2: Humulin-R Alone vs Stage 2: Humulin-R + rHuPH20: p = 0.0002, ANOVA

Population analysed: Participants who received at least 1 dose of Humalog alone, Humalog + rHuPH20, Humulin-R alone, or Humulin-R + rHuPH20 with evaluable tmax data.

Primary outcome: Maximum Serum Insulin Concentration (Cmax)

Time frame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2. Mean (Standard Deviation). Unit: Picomoles per liter

Measure	Stage 1: Humalog Alone n = 12	Stage 1: Humalog + rHuPH20 n = 12	Stage 2: Humulin-R Alone n = 13	Stage 2: Humulin-R + rHuPH20 n = 13
Value	680 (361)	1290 (471)	390 (137)	944 (257)

Stage 1: Humalog Alone vs Stage 1: Humalog + rHuPH20: p = 0.0003, ANOVA
Stage 2: Humulin-R Alone vs Stage 2: Humulin-R + rHuPH20: p <0.0001, ANOVA

Population analysed: Participants who received at least 1 dose of Humalog alone, Humalog + rHuPH20, Humulin-R alone, or Humulin-R + rHuPH20 with evaluable Cmax data.

Primary outcome: Area Under the Serum Concentration-Time Curve From Time Zero to the Time Required to Reach Endogenous Plasma Glucose Levels (AUC[0-t'])

Time frame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2. Mean (Standard Deviation). Unit: Picomoles per liter times minutes

Measure	Stage 1: Humalog Alone n = 12	Stage 1: Humalog + rHuPH20 n = 12	Stage 2: Humulin-R Alone n = 13	Stage 2: Humulin-R + rHuPH20 n = 13
Value	116000 (23000)	133000 (21800)	91400 (25700)	137000 (32800)

Stage 1: Humalog Alone vs Stage 1: Humalog + rHuPH20: p = 0.0401, ANOVA
Stage 2: Humulin-R Alone vs Stage 2: Humulin-R + rHuPH20: p = 0.0004, ANOVA

Population analysed: Participants who received at least 1 dose of Humalog alone, Humalog + rHuPH20, Humulin-R alone, or Humulin-R + rHuPH20 with evaluable AUC(0-t') data.

Primary outcome: Area Under the Concentration-Time Curve From Time 0 to Time to Reach Maximum Concentration (Tmax) for Serum Insulin With Recombinant Human Hyaluronidase PH20 (rHuPH20) (AUC[0-tmaxPH20])

Time frame: Predose and up to 48 minutes postdose during Stage 1, or up to 68 minutes postdose during Stage 2. Mean (Standard Deviation). Unit: Picomoles per liter times minutes

Measure	Stage 1: Humalog Alone n = 12	Stage 1: Humalog + rHuPH20 n = 12	Stage 2: Humulin-R Alone n = 13	Stage 2: Humulin-R + rHuPH20 n = 13
Value	9530 (10500)	27900 (14300)	8780 (3010)	34800 (9150)

Stage 1: Humalog Alone vs Stage 1: Humalog + rHuPH20: p <0.0001, ANOVA
Stage 2: Humulin-R Alone vs Stage 2: Humulin-R + rHuPH20: p <0.0001, ANOVA

Population analysed: Participants who received at least 1 dose of Humalog alone, Humalog + rHuPH20, Humulin-R alone, or Humulin-R + rHuPH20 with evaluable AUC(0-tmaxPH20) data.

9 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: Humalog Alone	0 of 12 (0%)	3 of 12 (25%)	Not reported
Stage 1: Humalog + rHuPH20	0 of 12 (0%)	3 of 12 (25%)	Not reported
Stage 2: Humulin-R Alone	0 of 13 (0%)	2 of 13 (15.4%)	Not reported
Stage 2: Humulin-R + rHuPH20	0 of 14 (0%)	3 of 14 (21.4%)	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 19459762Vaughn DE, Yocum RC, Muchmore DB, Sugarman BJ, Vick AM, Bilinsky IP, Frost GI. Accelerated pharmacokinetics and glucodynamics of prandial insulins injected with recombinant human hyaluronidase. Diabetes Technol Ther. 2009 Jun;11(6):345-52. doi: 10.1089/dia.2009.0013.

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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.

Mark S. Kipnes, MD principal investigator

Diabetes and Glandular Disease Research Associates 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 Humalog, Humulin-R and Recombinant human hyaluronidase PH20 (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 8 inclusion and 15 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 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 14 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?

Time to Maximum Serum Insulin Concentration (Tmax) (time frame: Predose and up to 360 minutes postdose during Stage 1 or Stage 2). The study lists 5 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 NCT00705536, 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.