HealthyPhase 4NCT00311519
A Phase IIIB Dose Comparison Study of Subcutaneous Hydration With and Without Human Recombinant Hyaluronidase (HYLENEX) in Volunteer Subjects
A Phase 4 study testing Hylenex in people with Healthy, run by Halozyme Therapeutics at 1 site in United States.
Trial summary
The purpose of this research study to test the effectiveness of a study medication to increase how fast a solution called lactated Ringer's is absorbed when put under the skin subcutaneously. The medication to be studied is an enzyme called hyaluronidase, and is a human recombinant form of the enzyme. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Hylenex
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2005to Jan 2006
- Phase
- Phase 4
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males or females aged 18 to 60 years, inclusive
- Agreement that there will be no fluid intake for 12 hours prior to the start of the study infusion (except sips of water to take necessary medications)
- Vital signs (BP, HR, RR) within normal range
- Metabolic panel (e.g., sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, calcium, AST, ALT, alkaline phosphatase, total bilirubin, albumin, and total protein) within normal range within 7 days of infusion
- Adequate venous access in at least one forearm
- A negative pregnancy test (if female of child-bearing potential) within 7 days of infusion
- Decision-making capacity
- Signed, written IRB-approved informed consent
Who cannot join
- Extremity edema
- Upper extremity pathology that could interfere with study outcome (e.g., cellulitis, lymphatic disorder or prior surgery, pre-existing pain syndrome, previous mastectomy and/or axillary lymph node dissection, etc.)
- History of cardiovascular disease
- Rales on lung auscultation
- Known allergy to hyaluronidase or any other ingredient in the formulation of HYLENEX
- Known allergy to bee or vespid venom
- Known coagulopathy
Trial locations and contacts
1 site in 1 country.
United States1 site
West Coast Clinical Trials
Long Beach, California, 90806-2325
About this study
Official title: A Phase IIIB Double Blind, Randomized, Placebo-Controlled, Dose-Comparison Study of Subcutaneous Hydration With and Without Human Recombinant Hyaluronidase (HYLENEX) in Volunteer Subjects
The purpose of this research study to test the effectiveness of a study medication to increase how fast a solution called lactated Ringer's is absorbed when put under the skin subcutaneously. The medication to be studied is an enzyme called hyaluronidase, and is a human recombinant form of the enzyme. The drug company name for this medication is Hylenex. Hylenex was currently an investigational medication at the initiation of the study, but received FDA approval during the study. An investigational medication is a medication or formulation of a medication that is not approved by the United States Food and Drug Administration for use in this country but may be used in studies such as this one.
Read the detailed description
The study will be conducted in two sequential stages:
Stage 1: Preliminary assessment of mean flow rate and its inter-subject variability, and a comparison to IV infusion. Each subject will receive a SC infusion of 400 mL (from a 0.5 L bag) of Ringer's lactate solution in each upper arm, followed by one IV infusion of 400 mL of Ringer's lactate solution (from a 0.5 L bag). The SC injection sites will be randomized in a double-blinded fashion to receive either 150 units Hylenex or an equal volume of saline placebo injected into a Y-port in the tubing just above the catheter immediately prior to infusion. 24-gauge angiocatheters will be placed symmetrically in the SC space in both proximal upper extremities at the lateral aspect, midline halfway between the olecranon process and the inferoposterior aspect of the acromion, introduced at a 30-degree angle. A 24-gauge angiocatheter will also be placed in a vein in either the left or right forearm (per randomization). In each upper arm, Ringer's lactate solution will be infused SC by gravity (wide open) by placing the top of the fluid in a 0.5 liter bag at a height of 100 cm above the respective angiocatheter sites. After completion of both SC infusions, Ringer's lactate solution will be infused IV by gravity (wide open) by placing the top of the fluid in a 0.5 liter bag at a height of 100 cm above the angiocatheter sites. The flow rate observations in Stage 1 will be used to either confirm or adjust the proposed sample size for Stage 2, if such adjustment is necessary.
Stage 2: Dose-comparison assessment of rate of flow over the range of 150 to 1,500 units of Hylenex. Each subject will receive a SC infusion of 400 mL (from a 0.5 L bag) of Ringer's lactate solution in each upper arm. The SC injection sites will be randomized in a double-blinded fashion to either Hylenex or an equal volume of saline solution injected into a Y-port in the tubing just above the catheter immediately prior to infusion. 24-gauge angiocatheters will be placed symmetrically in the SC space in both proximal upper extremities at the lateral aspect, midline halfway between the olecranon process and the inferoposterior aspect of the acromion, introduced at a 30-degree angle. In each arm, Ringer's lactate solution will be infused SC by gravity (wide open) by placing the top of the fluid in a 0.5 liter bag at a height of 100 cm above the respective catheter sites. Subjects will be dosed in either two or three sequential cohorts.
Cohort 3, at 750 U, to be conducted ONLY if flow rate for Cohort 2 is at least 20% faster than for Cohort 1 without unacceptable toxicity in Cohort 1, or unacceptable toxicity observed in Cohort 2 and not Cohort
In each stage, safety and tolerability will be assessed through physical examination targeted at infusion sites and volume status assessment, vital signs, and adverse events.
Study Medications Hylenex recombinant (hyaluronidase human injection); rHuPH20 (Hylenex is a registered trademark of Baxter International, Inc. or its subsidiaries)
Duration: In both stages of the study, subjects who are successfully screened for the study will receive a single, one-day session of study drug administration followed by parenteral infusions, and then undergo follow-up evaluations at 1 day (in clinic) and 28 days (by telephone) after treatment.
Subject Population: Normal volunteers satisfying all entry criteria.
Planned Total Sample Size: Considering both stages, no more than a total of 70 subjects may be enrolled in this study.
Stage 1: Five evaluable subjects will be enrolled. It is anticipated that no more than a total of 10 subjects will need to be enrolled to provide 5 evaluable subjects. An evaluable subject is one who completes all 3 parenteral infusions. Subjects not meeting this criterion, including those withdrawn prematurely for reasons other than toxicity, will be replaced.
Stage 2: 15 evaluable subjects per cohort will be enrolled. An evaluable subject is one who has completed both SC infusions and has completed protocol-specified assessments sufficient for determination of safety and tolerability. Subjects not meeting these criteria, including those withdrawn prematurely for reasons other than toxicity, will be replaced. Enrollment of Cohort 3 is dependent on findings in Cohorts 1 and 2. Allowing for some non-evaluable subjects in up to three cohorts, each including 15 evaluable subjects, a total of up to 60 subjects may be entered in this Stage 2.
Stopping Rules: Safety monitoring of enrolled subjects will be ongoing and continuous. If signs or symptoms of unacceptable fluid overload occur, the subject will be withdrawn.
- Conditions
- Healthy
- Being tested
- Hylenex
- Keywords
- Subcutaneous hydration, Hylenex, Hyaluronidase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HylenexDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Average infusion flow rate (mL/hr) derived from the time to infuse 400 mL of lactated ringers
Secondary outcomes (11)
Average SC infusion rate of flow (mL/hr) derived from time required to drain 400 mL from the 500 mL infusate bag, fluid and tubing AND for the arm circumference to return to baseline
Flow rate determined by weight of infusate bag, fluid and tubing at specified timepoints
For SC infusions, change in arm circumference in three locations in the vicinity of the site of infusion
For SC infusions, time from the beginning of infusion until arm circumference returns to baseline
Subject assessment of local discomfort by placing a mark on a 0 100 mm visual analogue scale (VAS) anchored by no discomfort and worst possible discomfort
Local edema assessed by the Investigator on a 0-4 scale
Leakage of fluid at angiocatheter site assessed by the Investigator on a 0-4 scale, prior to infusion, at mid-infusion, at end of infusion, and (for SC infusions), when arm circumference returns to baseline
Subject's global rank-ordered preference for infusion
Investigator's global rank-ordered preference for infusion
Photographic images of the SC infusion sites
Safety and tolerability, based on adverse events and PE including vital signs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2006 (estimated)
- Study startNov 2005
- Study completionJan 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 50 participants
Sponsor and investigators
- Lead sponsor
- Halozyme Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Javier T Quesada, OD, Principal investigator, West Coast Clinical Trials
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00311519
- Sponsor's protocol ID
- HZ2-05-04
- Status last verified
- Apr 2006
- First submitted
- 4 Apr 2006
- Last updated
- 6 Apr 2006
- Results posted
- No
Publications
Thomas JR, Yocum RC, Haller MF, Flament J. The INFUSE-Morphine IIB study: use of recombinant human hyaluronidase (rHuPH20) to enhance the absorption of subcutaneous morphine in healthy volunteers. J Pain Symptom Manage. 2009 Nov;38(5):673-82. doi: 10.1016/j.jpainsymman.2009.03.010. Epub 2009 Oct 12.
PubMed 19819667
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIIB Double Blind, Randomized, Placebo-Controlled, Dose-Comparison Study of Subcutaneous Hydration With and Without Human Recombinant Hyaluronidase (HYLENEX) in Volunteer Subjects
- ClinicalTrials.gov ID
- NCT00311519
- Acronym / sponsor ID
- HZ2-05-04
- Conditions
- Healthy
- Keywords
- Subcutaneous hydration, Hylenex, Hyaluronidase
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- Halozyme TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Nov 2005
- Study completion
- Jan 2006
- First posted
- 6 Apr 2006 (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.
The purpose of this research study to test the effectiveness of a study medication to increase how fast a solution called lactated Ringer's is absorbed when put under the skin subcutaneously. The medication to be studied is an enzyme called hyaluronidase, and is a human recombinant form of the enzyme. The drug company name for this medication is Hylenex. Hylenex was currently an investigational medication at the initiation of the study, but received FDA approval during the study. An investigational medication is a medication or formulation of a medication that is not approved by the United States Food and Drug Administration for use in this country but may be used in studies such as this one.
Detailed description
The study will be conducted in two sequential stages:
Stage 1: Preliminary assessment of mean flow rate and its inter-subject variability, and a comparison to IV infusion. Each subject will receive a SC infusion of 400 mL (from a 0.5 L bag) of Ringer's lactate solution in each upper arm, followed by one IV infusion of 400 mL of Ringer's lactate solution (from a 0.5 L bag). The SC injection sites will be randomized in a double-blinded fashion to receive either 150 units Hylenex or an equal volume of saline placebo injected into a Y-port in the tubing just above the catheter immediately prior to infusion. 24-gauge angiocatheters will be placed symmetrically in the SC space in both proximal upper extremities at the lateral aspect, midline halfway between the olecranon process and the inferoposterior aspect of the acromion, introduced at a 30-degree angle. A 24-gauge angiocatheter will also be placed in a vein in either the left or right forearm (per randomization). In each upper arm, Ringer's lactate solution will be infused SC by gravity (wide open) by placing the top of the fluid in a 0.5 liter bag at a height of 100 cm above the respective angiocatheter sites. After completion of both SC infusions, Ringer's lactate solution will be infused IV by gravity (wide open) by placing the top of the fluid in a 0.5 liter bag at a height of 100 cm above the angiocatheter sites. The flow rate observations in Stage 1 will be used to either confirm or adjust the proposed sample size for Stage 2, if such adjustment is necessary.
Stage 2: Dose-comparison assessment of rate of flow over the range of 150 to 1,500 units of Hylenex. Each subject will receive a SC infusion of 400 mL (from a 0.5 L bag) of Ringer's lactate solution in each upper arm. The SC injection sites will be randomized in a double-blinded fashion to either Hylenex or an equal volume of saline solution injected into a Y-port in the tubing just above the catheter immediately prior to infusion. 24-gauge angiocatheters will be placed symmetrically in the SC space in both proximal upper extremities at the lateral aspect, midline halfway between the olecranon process and the inferoposterior aspect of the acromion, introduced at a 30-degree angle. In each arm, Ringer's lactate solution will be infused SC by gravity (wide open) by placing the top of the fluid in a 0.5 liter bag at a height of 100 cm above the respective catheter sites. Subjects will be dosed in either two or three sequential cohorts.
Cohort 3, at 750 U, to be conducted ONLY if flow rate for Cohort 2 is at least 20% faster than for Cohort 1 without unacceptable toxicity in Cohort 1, or unacceptable toxicity observed in Cohort 2 and not Cohort
In each stage, safety and tolerability will be assessed through physical examination targeted at infusion sites and volume status assessment, vital signs, and adverse events.
Study Medications Hylenex recombinant (hyaluronidase human injection); rHuPH20 (Hylenex is a registered trademark of Baxter International, Inc. or its subsidiaries)
Duration: In both stages of the study, subjects who are successfully screened for the study will receive a single, one-day session of study drug administration followed by parenteral infusions, and then undergo follow-up evaluations at 1 day (in clinic) and 28 days (by telephone) after treatment.
Subject Population: Normal volunteers satisfying all entry criteria.
Planned Total Sample Size: Considering both stages, no more than a total of 70 subjects may be enrolled in this study.
Stage 1: Five evaluable subjects will be enrolled. It is anticipated that no more than a total of 10 subjects will need to be enrolled to provide 5 evaluable subjects. An evaluable subject is one who completes all 3 parenteral infusions. Subjects not meeting this criterion, including those withdrawn prematurely for reasons other than toxicity, will be replaced.
Stage 2: 15 evaluable subjects per cohort will be enrolled. An evaluable subject is one who has completed both SC infusions and has completed protocol-specified assessments sufficient for determination of safety and tolerability. Subjects not meeting these criteria, including those withdrawn prematurely for reasons other than toxicity, will be replaced. Enrollment of Cohort 3 is dependent on findings in Cohorts 1 and 2. Allowing for some non-evaluable subjects in up to three cohorts, each including 15 evaluable subjects, a total of up to 60 subjects may be entered in this Stage 2.
Stopping Rules: Safety monitoring of enrolled subjects will be ongoing and continuous. If signs or symptoms of unacceptable fluid overload occur, the subject will be withdrawn.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Males or females aged 18 to 60 years, inclusive
- Agreement that there will be no fluid intake for 12 hours prior to the start of the study infusion (except sips of water to take necessary medications)
- Vital signs (BP, HR, RR) within normal range
- Metabolic panel (e.g., sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, calcium, AST, ALT, alkaline phosphatase, total bilirubin, albumin, and total protein) within normal range within 7 days of infusion
- Adequate venous access in at least one forearm
Key exclusion criteria (7 listed)
- Extremity edema
- Upper extremity pathology that could interfere with study outcome (e.g., cellulitis, lymphatic disorder or prior surgery, pre-existing pain syndrome, previous mastectomy and/or axillary lymph node dissection, etc.)
- History of cardiovascular disease
- Rales on lung auscultation
- Known allergy to hyaluronidase or any other ingredient in the formulation of HYLENEX
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 |
|---|---|---|
| Hylenex | Drug | – |
Primary outcome
Average infusion flow rate (mL/hr) derived from the time to infuse 400 mL of lactated ringers
11 secondary outcomes
Average SC infusion rate of flow (mL/hr) derived from time required to drain 400 mL from the 500 mL infusate bag, fluid and tubing AND for the arm circumference to return to baseline
Flow rate determined by weight of infusate bag, fluid and tubing at specified timepoints
For SC infusions, change in arm circumference in three locations in the vicinity of the site of infusion
For SC infusions, time from the beginning of infusion until arm circumference returns to baseline
Subject assessment of local discomfort by placing a mark on a 0 100 mm visual analogue scale (VAS) anchored by no discomfort and worst possible discomfort
Local edema assessed by the Investigator on a 0-4 scale
Leakage of fluid at angiocatheter site assessed by the Investigator on a 0-4 scale, prior to infusion, at mid-infusion, at end of infusion, and (for SC infusions), when arm circumference returns to baseline
Subject's global rank-ordered preference for infusion
Investigator's global rank-ordered preference for infusion
Photographic images of the SC infusion sites
Safety and tolerability, based on adverse events and PE including vital signs
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 6 Apr 2006.
- Derived from this study: PubMed 19819667Thomas JR, Yocum RC, Haller MF, Flament J. The INFUSE-Morphine IIB study: use of recombinant human hyaluronidase (rHuPH20) to enhance the absorption of subcutaneous morphine in healthy volunteers. J Pain Symptom Manage. 2009 Nov;38(5):673-82. doi: 10.1016/j.jpainsymman.2009.03.010. Epub 2009 Oct 12.
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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.
Javier T Quesada, OD principal investigator
West Coast Clinical Trials
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hylenex in people with Healthy, 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 7 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 6 Apr 2006. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
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?
Average infusion flow rate (mL/hr) derived from the time to infuse 400 mL of lactated ringers. 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 NCT00311519, 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 6 Apr 2006.