Healthy VolunteersPhase 1NCT00803972
Dose-Ranging, Pharmacokinetic (PK), Glucodynamic (GD), Safety and Tolerability Study of Subcutaneously (SC) Administered Humulin R and Humalog With or Without rHuPH20
A Phase 1 study testing rHuPH20, Insulin Human Injection and Insulin Lispro Injection in people with Healthy Volunteers, run by Halozyme Therapeutics at 1 site in United States.
Trial summary
This is a single center, Phase I, open-label, single-blind (subjects blinded to the contents of each injection), 4 stage study designed to determine the PK, GD, safety, tolerability, and optimal ratio of rHuPH20 administered with fixed Humulin R or Humalog doses in healthy subjects. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- rHuPH20, Insulin Human Injection and Insulin Lispro Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2008to 28 Aug 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 subjects between the ages of 18 and 55 years, inclusive. (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination (PE), including blood pressure (BP) and heart rate (HR), 12-lead electrocardiogram (ECG) and clinical laboratory tests specified in these eligibility criteria).
- BMI between 18-28 kg/m2, inclusive.
- Total body weight >70 kg (154 lb) for men and 46 kg (101 lb) for women.
- Subject willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including adequate venous access.
- Vital signs (BP, HR, temperature, respiratory rate) within normal range or, if out of range, assessed by the Principal Investigator (PI) as not clinically significant (NCS) and mutually agreed by both PI and the Sponsor's medical monitor that the subject need not be excluded from the study for this abnormal value.
- Within 14 days before the first injection: metabolic panel (e.g., sodium, potassium, chloride, bicarbonate, BUN (blood urea nitrogen), creatinine, glucose, calcium, AST (aspartate transaminase [SGOT]), ALT (alanine transaminase [SGPT]), alkaline phosphatase, total bilirubin, albumin, cholesterol, lipids, amylase and total protein) and complete blood count (CBC) within the laboratory normal reference range or, if out of range, assessed by the PI as NCS and mutually agreed by both PI and the Sponsor's medical monitor that the subject need not be excluded from the study for this laboratory value.
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- Fasting plasma glucose level within the range of 60 to 100 mg/dL, inclusive, within 30 minutes of the first euglycemic clamp.
- A negative serum pregnancy test (if female of childbearing potential) within 14 days of study drug injection.
- Female subjects 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.
- Decision-making capacity and willingness and ability to comply with the requirements for full completion of the study.
- Signed, written 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 drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Clinical significance to be determined by the PI.
- Known history of diabetes mellitus or gestational diabetes.
- Known allergy to hyaluronidase or any other ingredient in the study drug.
- Positive HIV 1 and HIV 2 (human immunodeficiency virus) antibody test, hepatitis B (anti-HBsAg) or hepatitis C (anti-HCV) antibody test.
- 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, screening quantitative urine nicotine concentration >50 ng/mL, or screening serum cotinine concentration of > 20 ng/mL.
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- 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 mL within 56 days before dosing.
- Failure to limit alcohol consumption and refrain from exercise within 48 hours before each injection.
- Participation in a study of any investigational drug or device 30 days before enrollment in this study.
- The subject 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.
About this study
Official title: A Phase I, Randomized, Dose-Ranging, Pharmacokinetic, Glucodynamic, Safety, and Tolerability Study of SC Administered Humulin R and Humalog With or Without Recombinant Human Hyaluronidase (rHuPH20) in Healthy Volunteers
This is a single center, Phase I, open-label, single-blind (subjects blinded to the contents of each injection), 4 stage study designed to determine the PK, GD, safety, tolerability, and optimal ratio of rHuPH20 administered with fixed Humulin R or Humalog doses in healthy subjects.
Read the detailed description
Subjects will be enrolled in one of four sequential study stages. In each stage, a euglycemic clamp procedure will be used to control plasma glucose levels. Blood samples will be collected over an 8-hour time period after insulin administration (either Humulin R or Humalog) to analyze insulin and glucose levels using fully validated methods. Glucose infusion rates (GIR) will be recorded throughout the study period. The study is single-blind, with study subjects blinded as to the contents of each injection.
Determine the pharmacokinetics (PK) and optimum ratio of rHuPH20:insulin when a range of rHuPH20 dose ratios are administered subcutaneously (SC) with fixed doses of Humulin R, by determining Tmax, Cmax, AUCs, and relative bioavailability based on serum insulin concentrations collected at specified time points (Stage 1).
Determine if different concentrations of Humulin R impact the PK and minimal rHuPH20 dose necessary to achieve full insulin PK effect over a representative range of typical prandial SC Humulin R doses using the rHuPH20:insulin ratio identified in Stage 1 (Stage 2).
Determine the PK and optimum ratio of rHuPH20:insulin when a range of rHuPH20 dose ratios are administered SC with fixed doses of Humalog, by determining Tmax, Cmax, AUCs, and relative bioavailability based on serum insulin concentrations collected at specified time points (Stage 3).
Determine if different concentrations of Humalog impact the PK and minimal rHuPH20 dose necessary to achieve full insulin PK effect over a representative range of typical prandial SC Humalog doses using the rHuPH20:insulin ratio identified in Stage 3 (Stage 4).
Evaluate the safety and local tolerability of the SC injection at various rHuPH20, Humulin R, and Humalog doses (Stages 1 - 4).
Assess the glucodynamics (GD) of the SC injection of various rHuPH20, Humulin R, and Humalog doses (Stages 1 - 4).
- Conditions
- Healthy Volunteers
- Being tested
- rHuPH20, Insulin Human Injection, Insulin Lispro Injection
- Keywords
- Humalog, Humulin R, rHuPH20, Hylenex
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rHuPH20Drug
recombinant human hyaluronidase PH20
Insulin Human InjectionDrug
Also called Humulin® R
injection
Insulin Lispro InjectionDrug
Also called Humalog®
injection
| Study group | Role | What they receive |
|---|---|---|
| Stage 1: 3 U insulin plus rHuPH20 | Experimental | Participants will receive 3 Units (U) of regular insulin (100 U/milliliter [mL]), coadministered with sequential concentrations of 0, 1.25, 5, 10, 20, and 80 micrograms (μg)/mL recombinant human hyaluronidase (rHuPH20). Receives: Drug: rHuPH20; Drug: Insulin Human Injection |
| Stage 1: 12 U insulin plus rHuPH20 | Experimental | Participants will receive 12 U of regular insulin (100 U/mL), coadministered with sequential concentrations of 0, 1.25, 5, 10, 20, and 80 μg/mL rHuPH20. Receives: Drug: rHuPH20; Drug: Insulin Human Injection |
| Stage 2: insulin plus rHuPH20 | Experimental | Participants will receive 6, 12, and 24 U regular insulin (100 U/mL) in a randomly assigned order, with each insulin dose administered once with and once without 5 μg/mL rHuPH20. Receives: Drug: rHuPH20; Drug: Insulin Human Injection |
| Stage 3: 1.5 U insulin lispro plus rHuPH20 | Experimental | Participants will receive 1.5 U of insulin lispro (50 U/mL), coadministered with sequential concentrations of 0, 0.0625, 0.3125, 1.25, 5, and 20 μg/mL rHuPH20. Receives: Drug: rHuPH20; Drug: Insulin Lispro Injection |
| Stage 3: 6 U insulin lispro plus rHuPH20 | Experimental | Participants will receive 6 U of insulin lispro (50 U/mL), coadministered with sequential concentrations of 0, 0.0625, 0.3125, 1.25, 5, and 20 μg/mL rHuPH20. Receives: Drug: rHuPH20; Drug: Insulin Lispro Injection |
| Stage 4: 95 U/mL insulin lispro plus 5 μg/mL rHuPH20 | Experimental | Participants will receive 95 U/mL insulin lispro, administered once with and once without 5 μg/mL rHuPH20. At each insulin lispro concentration, participants will receive 2, 6, and 20 U lispro. Receives: Drug: rHuPH20; Drug: Insulin Lispro Injection |
| Stage 4: 50 U/mL insulin lispro plus 5 μg/mL rHuPH20 | Experimental | Participants will receive 50 U/mL insulin lispro, administered once with and once without 5 μg/mL rHuPH20. At each insulin lispro concentration, participants will receive 2, 6, and 20 U lispro. Receives: Drug: rHuPH20; Drug: Insulin Lispro Injection |
| Stage 4: 25 U/mL insulin lispro plus 5 μg/mL rHuPH20 | Experimental | Participants will receive 25 U/mL insulin lispro, administered once with and once without 5 μg/mL rHuPH20. At each insulin lispro concentration, participants will receive 2, 6, and 20 U lispro. Receives: Drug: rHuPH20; Drug: Insulin Lispro Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin AUC
Measured: 0 to 60 minutes
Secondary outcomes (1)
Other insulin PK, GD and safety outcomes
Measured: Day of each injection and 7 days after final dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2008 (estimated)
- Study startNov 2008
- Primary completion28 Aug 2009
- Study completion28 Aug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Halozyme Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jolene K Berg, MD, Principal investigator, dgd Research, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00803972
- Sponsor's protocol ID
- HZ2-08-04
- Status last verified
- Aug 2018
- First submitted
- 4 Dec 2008
- Last updated
- 15 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomized, Dose-Ranging, Pharmacokinetic, Glucodynamic, Safety, and Tolerability Study of SC Administered Humulin R and Humalog With or Without Recombinant Human Hyaluronidase (rHuPH20) in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT00803972
- Acronym / sponsor ID
- HZ2-08-04
- Conditions
- Healthy Volunteers
- Keywords
- Humalog, Humulin R, rHuPH20, Hylenex
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Halozyme TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Nov 2008
- Primary completion
- 28 Aug 2009 (actual)
- Study completion
- 28 Aug 2009 (actual)
- First posted
- 8 Dec 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single center, Phase I, open-label, single-blind (subjects blinded to the contents of each injection), 4 stage study designed to determine the PK, GD, safety, tolerability, and optimal ratio of rHuPH20 administered with fixed Humulin R or Humalog doses in healthy subjects.
Detailed description
Subjects will be enrolled in one of four sequential study stages. In each stage, a euglycemic clamp procedure will be used to control plasma glucose levels. Blood samples will be collected over an 8-hour time period after insulin administration (either Humulin R or Humalog) to analyze insulin and glucose levels using fully validated methods. Glucose infusion rates (GIR) will be recorded throughout the study period. The study is single-blind, with study subjects blinded as to the contents of each injection.
Determine the pharmacokinetics (PK) and optimum ratio of rHuPH20:insulin when a range of rHuPH20 dose ratios are administered subcutaneously (SC) with fixed doses of Humulin R, by determining Tmax, Cmax, AUCs, and relative bioavailability based on serum insulin concentrations collected at specified time points (Stage 1).
Determine if different concentrations of Humulin R impact the PK and minimal rHuPH20 dose necessary to achieve full insulin PK effect over a representative range of typical prandial SC Humulin R doses using the rHuPH20:insulin ratio identified in Stage 1 (Stage 2).
Determine the PK and optimum ratio of rHuPH20:insulin when a range of rHuPH20 dose ratios are administered SC with fixed doses of Humalog, by determining Tmax, Cmax, AUCs, and relative bioavailability based on serum insulin concentrations collected at specified time points (Stage 3).
Determine if different concentrations of Humalog impact the PK and minimal rHuPH20 dose necessary to achieve full insulin PK effect over a representative range of typical prandial SC Humalog doses using the rHuPH20:insulin ratio identified in Stage 3 (Stage 4).
Evaluate the safety and local tolerability of the SC injection at various rHuPH20, Humulin R, and Humalog doses (Stages 1 - 4).
Assess the glucodynamics (GD) of the SC injection of various rHuPH20, Humulin R, and Humalog doses (Stages 1 - 4).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Stage 1: 3 U insulin plus rHuPH20 | Experimental | Drug: rHuPH20, Drug: Insulin Human InjectionParticipants will receive 3 Units (U) of regular insulin (100 U/milliliter [mL]), coadministered with sequential concentrations of 0, 1.25, 5, 10, 20, and 80 micrograms (μg)/mL recombinant human hyaluronidase (rHuPH20). |
| Stage 1: 12 U insulin plus rHuPH20 | Experimental | Drug: rHuPH20, Drug: Insulin Human InjectionParticipants will receive 12 U of regular insulin (100 U/mL), coadministered with sequential concentrations of 0, 1.25, 5, 10, 20, and 80 μg/mL rHuPH20. |
| Stage 2: insulin plus rHuPH20 | Experimental | Drug: rHuPH20, Drug: Insulin Human InjectionParticipants will receive 6, 12, and 24 U regular insulin (100 U/mL) in a randomly assigned order, with each insulin dose administered once with and once without 5 μg/mL rHuPH20. |
| Stage 3: 1.5 U insulin lispro plus rHuPH20 | Experimental | Drug: rHuPH20, Drug: Insulin Lispro InjectionParticipants will receive 1.5 U of insulin lispro (50 U/mL), coadministered with sequential concentrations of 0, 0.0625, 0.3125, 1.25, 5, and 20 μg/mL rHuPH20. |
| Stage 3: 6 U insulin lispro plus rHuPH20 | Experimental | Drug: rHuPH20, Drug: Insulin Lispro InjectionParticipants will receive 6 U of insulin lispro (50 U/mL), coadministered with sequential concentrations of 0, 0.0625, 0.3125, 1.25, 5, and 20 μg/mL rHuPH20. |
| Stage 4: 95 U/mL insulin lispro plus 5 μg/mL rHuPH20 | Experimental | Drug: rHuPH20, Drug: Insulin Lispro InjectionParticipants will receive 95 U/mL insulin lispro, administered once with and once without 5 μg/mL rHuPH20. At each insulin lispro concentration, participants will receive 2, 6, and 20 U lispro. |
| Stage 4: 50 U/mL insulin lispro plus 5 μg/mL rHuPH20 | Experimental | Drug: rHuPH20, Drug: Insulin Lispro InjectionParticipants will receive 50 U/mL insulin lispro, administered once with and once without 5 μg/mL rHuPH20. At each insulin lispro concentration, participants will receive 2, 6, and 20 U lispro. |
| Stage 4: 25 U/mL insulin lispro plus 5 μg/mL rHuPH20 | Experimental | Drug: rHuPH20, Drug: Insulin Lispro InjectionParticipants will receive 25 U/mL insulin lispro, administered once with and once without 5 μg/mL rHuPH20. At each insulin lispro concentration, participants will receive 2, 6, and 20 U lispro. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Healthy subjects between the ages of 18 and 55 years, inclusive. (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination (PE), including blood pressure (BP) and heart rate (HR), 12-lead electrocardiogram (ECG) and clinical laboratory tests specified in these eligibility criteria).
- BMI between 18-28 kg/m2, inclusive.
- Total body weight >70 kg (154 lb) for men and 46 kg (101 lb) for women.
- Subject willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including adequate venous access.
- Vital signs (BP, HR, temperature, respiratory rate) within normal range or, if out of range, assessed by the Principal Investigator (PI) as not clinically significant (NCS) and mutually agreed by both PI and the Sponsor's medical monitor that the subject need not be excluded from the study for this abnormal value.
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 drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Clinical significance to be determined by the PI.
- Known history of diabetes mellitus or gestational diabetes.
- Known allergy to hyaluronidase or any other ingredient in the study drug.
- Positive HIV 1 and HIV 2 (human immunodeficiency virus) antibody test, hepatitis B (anti-HBsAg) or hepatitis C (anti-HCV) antibody test.
- Any history or evidence of alcohol or drug abuse.
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 |
|---|---|---|
| rHuPH20recombinant human hyaluronidase PH20 | Drug | Stage 1: 12 U insulin plus rHuPH20, Stage 1: 3 U insulin plus rHuPH20, Stage 2: insulin plus rHuPH20, Stage 3: 1.5 U insulin lispro plus rHuPH20, Stage 3: 6 U insulin lispro plus rHuPH20, Stage 4: 25 U/mL insulin lispro plus 5 μg/mL rHuPH20, Stage 4: 50 U/mL insulin lispro plus 5 μg/mL rHuPH20, Stage 4: 95 U/mL insulin lispro plus 5 μg/mL rHuPH20 |
| Insulin Human InjectionAlso: Humulin® Rinjection | Drug | Stage 1: 12 U insulin plus rHuPH20, Stage 1: 3 U insulin plus rHuPH20, Stage 2: insulin plus rHuPH20 |
| Insulin Lispro InjectionAlso: Humalog®injection | Drug | Stage 3: 1.5 U insulin lispro plus rHuPH20, Stage 3: 6 U insulin lispro plus rHuPH20, Stage 4: 25 U/mL insulin lispro plus 5 μg/mL rHuPH20, Stage 4: 50 U/mL insulin lispro plus 5 μg/mL rHuPH20, Stage 4: 95 U/mL insulin lispro plus 5 μg/mL rHuPH20 |
Primary outcome
Insulin AUC
Time frame: 0 to 60 minutes
1 secondary outcome
Other insulin PK, GD and safety outcomes
Time frame: Day of each injection and 7 days after final dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2018.
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Screening Protocol
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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.
Jolene K Berg, MD principal investigator
dgd 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 rHuPH20, Insulin Human Injection and Insulin Lispro Injection in people with Healthy Volunteers, 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 11 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 15 Aug 2018. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Insulin AUC (time frame: 0 to 60 minutes). 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 15 Aug 2018.