INFUSE Morphine Study (INFUSE)

INcreased Flow Utilizing Subcutaneously Enabled Morphine (INFUSE-Morphine) With and Without Human Recombinant Hyaluronidase (HYLENEX) and Intravenously

Double-blind study comparing the pharmacokinetics, safety and tolerability of morphine administered subcutaneously (SC) with and without human recombinant hyaluronidase (HYLENEX) and intravenously conducted in patients in a hospice care setting or through a palliative care medicine setting. In this within-patient controlled study, each eligible study patient receives a single injection by each of the three methods of morphine administration, sequentially on three consecutive days, according to the order specified by a randomization schedule.

Each of the three injections consists of 5 mg of morphine (1.0 mL of 5 mg/mL solution). The HYLENEX injection will be 1 mL of 150 units. Although the IV administration will not be blinded, the two SC injections will be double-blinded, using the same volume of normal saline (0.9% sodium chloride) placebo (1.0 mL) as HYLENEX.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Hylenex

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92037
      • UCSD Thornton Hospital
    • San Diego, California, United States, 92103
      • San Diego Hospice and Palliative Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females at least 18 years of age who are patients of San Diego Hospice & Palliative Care or recruited through San Diego Hospice & Palliative Care or the UCSD Center for Pain and Palliative Medicine.
2. During the treatment days of the study, on opioid therapy other than morphine that is equivalent to ≥ 60 mg oral morphine per day and without unacceptable toxicity.
3. Vital signs (BP, HR, RR) within normal range.
4. Adequate venous access in both upper extremities.
5. A negative pregnancy test (if female of child-bearing potential) within 7 days prior to first injection.
6. Life expectancy ≥ ten days.
7. Decision-making capacity.
8. Signed, written IRB-approved informed consent. -

Exclusion Criteria:

1. Known hypersensitivity or history of any toxicity to morphine.
2. Morphine within the 4 days prior to the first study medication injection or anticipated to be receiving morphine during any of the treatment days in this study.
3. Any contraindication to morphine.
4. Known hypersensitivity to naloxone.
5. Known allergy to hyaluronidase or any other ingredient in the formulation of HYLENEX.
6. Known allergy to bee or vespid venom.
7. Contraindication to IV heparin lock or known hypersensitivity to heparin.
8. Edema, infection, or any other lower extremity or pelvic disorder that might affect subcutaneous absorption from the thigh.
9. Hemoglobin < 10 g/dL.
10. Presence of any other medical condition that would present an unacceptable safety risk to the patient.
11. 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: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: 1; IV Morphine
Experimental: 2; SC Morphine with Hylenex	Drug: Hylenex; Add Hylenex to SC injection of Morphine
Active Comparator: 3; SC Morphine with Saline	Drug: Hylenex; Add Hylenex to SC injection of Morphine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
• Determine the Tmax and other pharmacokinetic parameters of morphine injected subcutaneously with HYLENEX compared to without HYLENEX and injected intravenously	29 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Compare the safety and tolerability of these three methods of injections of morphine	29 days

Collaborators and Investigators

• Sponsor: Halozyme Therapeutics
• Investigators: Principal Investigator: Jay Thomas, M.D., San Diego Hospice; Principal Investigator: Mark S Wallace, M.D., UCSD Thornton Hospital

Publications and helpful links

General Publications

• Thomas JR, Wallace MS, Yocum RC, Vaughn DE, Haller MF, Flament J. The INFUSE-Morphine study: use of recombinant human hyaluronidase (rHuPH20) to enhance the absorption of subcutaneously administered morphine in patients with advanced illness. J Pain Symptom Manage. 2009 Nov;38(5):663-72. doi: 10.1016/j.jpainsymman.2009.03.009. Epub 2009 Oct 12.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): October 1, 2006
• Study Completion (Actual): October 1, 2006

Study Registration Dates

• First Submitted: January 2, 2008
• First Submitted That Met QC Criteria: January 11, 2008
• First Posted (Estimate): January 14, 2008

Study Record Updates

• Last Update Posted (Estimate): January 14, 2008
• Last Update Submitted That Met QC Criteria: January 11, 2008
• Last Verified: January 1, 2008

More Information

Terms related to this study

• Keywords: morphine; subcutaneous; bioavailability; absorption; Hyaluronidase; Hylenex; PK study of morphine in patients with pain
• Other Study ID Numbers: HZ2-05-06; 05-015-MI (Hospice #)