Pharmacokinetic, Safety and Tolerability Study of SC Administered Bisphosphonate With rHuPH20 vs Bisphosphonate Alone

Phase I, Open-Label, Pharmacokinetic, Safety and Tolerability Study of Subcutaneously Administered Bisphosphonate With Recombinant Human Hyaluronidase (rHuPH20) vs Bisphosphonate

The purpose of this study is to determine the maximum tolerated concentration (MTC) of bisphosphonate with a fixed dose of rHuPH20 administered SC, the MTC of bisphosphonate without rHuPH20 administered SC, the optimal dose of rHuPH20 to deliver bisphosphonate SC at MTC, and to compare the PK of SC administered bisphosphonate at MTC with optimal dose rHuPH20 to bisphosphonate alone.

Study Overview

• Status: Completed
• Conditions: Risk Factors for or a Diagnosis of Osteoporosis
• Intervention / Treatment: Drug: rHuPH20; Drug: zoledronic acid

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78209
      • Healthcare Discoveries, LLC/ICON Development Solutions

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female volunteers 18 to 60 years of age, inclusive.
• Intact normal skin in the area intended for administration.
• Adequate venous access in both upper extremities.
• Dental examination by an appropriately trained professional within 14 days of administration demonstrating no signs, symptoms, or risk factors of osteonecrosis of the jaw (ONJ).
• Vital signs (BP, HR, temperature, respiratory rate) within normal range or, if out of range, assessed by the Investigator as not clinically significant and it is mutually agreed by both Investigator and Sponsor Medical Monitor that the subject need not be excluded from the study for this reason.
• Electrocardiogram within normal range or if out of range, assessed by the Investigator as not clinically significant and it is mutually agreed by both Investigator and Sponsor Medical Monitor that the subject need not be excluded from the study for this reason.
• Within 14 days prior to administration, metabolic panel (e.g., sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, calcium, AST, ALT, alkaline phosphatase, total bilirubin, albumin, and total protein) and complete blood count within the laboratory normal reference range or, if out of range, assessed by the Investigator as not clinically significant and it is mutually agreed by both Investigator and Sponsor Medical Monitor that the subject need not be excluded from the study for this laboratory value.
• A negative serum or urine pregnancy test (if female of child-bearing potential) within 14 days of study drug administration.
• Female subjects of child-bearing potential must agree to be currently practicing effective birth control or abstinence and agree to continue to do so for at least 30 days after duration of their time on study.
• Decision-making capacity and willingness and ability to comply with the requirements for full completion of the trial.
• Signed, written IRB/EC-approved informed consent.

Exclusion Criteria:

• Lower extremity edema.
• Lower extremity pathology that could interfere with any protocol-specified outcome assessment (e.g., cellulitis, lymphatic disorder or prior surgery, pre-existing pain syndrome, auxiliary lymph node dissection, etc.).
• Creatinine clearance < 60 mL/min (Cockcroft-Gault formula).
• Any risk factor for bisphosphonate-related renal toxicity including by not limited to known predisposition to or history of renal insufficiency or renal failure, hypertension, diabetes mellitus, volume depletion, sepsis, paraproteinemia, and subjects receiving known nephrotoxic drugs.
• Dehydration Grade 2 or higher based on NCI CTCAE V3.0.
• Known parathyroid gland dysfunction or any other disease that could lower blood calcium levels.
• Known history and/or electrocardiographic evidence of atrial fibrillation.
• Known allergy to any hyaluronidase.
• Bisphosphonate treatment within preceding six months.
• Known allergy or intolerance to any bisphosphonate.
• Pregnancy or breast-feeding woman.
• Known clinically significant cardiovascular, gastrointestinal, hepatic, neurological, psychiatric, endocrine, cancer, HIV infection, diabetes mellitus, intercurrent illness such as influenza, or other major systemic disease that would unduly risk the subject's safety or interfere with the interpretation of results.
• Participation in a study of any investigational drug or device within 30 days of enrollment in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1: rHuPH20 plus ZA; Participants will receive one of several dose/concentrations of recombinant human hyaluronidase PH20 (rHuPH20) with zoledronic acid (ZA).	Drug: rHuPH20; recombinant human hyaluronidase PH20 injection; Drug: zoledronic acid; subcutaneous injection
Experimental: Stage 2: ZA; Participants will receive a dose/concentration of ZA administered without rHuPH20.	Drug: zoledronic acid; subcutaneous injection
Experimental: Stage 3: rHuPH20 plus ZA; Participants will receive one of several dose/concentrations of rHuPH20 with ZA.	Drug: rHuPH20; recombinant human hyaluronidase PH20 injection; Drug: zoledronic acid; subcutaneous injection
Experimental: Stage 4: ZA; Participants will receive an intravenous (IV) dose of 5 milligrams (mg) ZA.	Drug: zoledronic acid; subcutaneous injection
Experimental: Stage 4: ZA with rHuPH20; Participants will receive a subcutaneous (SC) dose of ZA with rHuPH20.	Drug: rHuPH20; recombinant human hyaluronidase PH20 injection; Drug: zoledronic acid; subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assessment of local tolerability of injected drug product	Over a 7 day period

Collaborators and Investigators

• Sponsor: Halozyme Therapeutics
• Investigators: Principal Investigator: Emanuel P DeNoia, MD, Healthcare Discoveries, LLC/ICON

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): September 21, 2009
• Study Completion (Actual): September 21, 2009

Study Registration Dates

• First Submitted: December 11, 2008
• First Submitted That Met QC Criteria: December 11, 2008
• First Posted (Estimate): December 15, 2008

Study Record Updates

• Last Update Posted (Actual): August 15, 2018
• Last Update Submitted That Met QC Criteria: August 13, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Pharmacokinetics; rHuPH20
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: HZ2-08-02