A Phase IIIB Dose Comparison Study of Subcutaneous Hydration With and Without Human Recombinant Hyaluronidase (HYLENEX) in Volunteer Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 4

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. 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.
    

Intervention name(s): Hylenex
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Subcutaneous hydration; Hylenex; Hyaluronidase