Safety, Efficacy, and Pharmacokinetics of Amphotericin B Lipid Complex

Safety, Efficacy, and Pharmacokinetics of Amphotericin B Lipid Complex at 10 mg/kg/d for 7 Days or 5.0 mg/kg/d for 14 Days as Induction Therapy for Disseminated Cryptococcosis in Patients With HIV

The purpose of this study is to determine if initial therapy with ABLC at 10/mg/kg/d for 7 days are at least effective as ABLC at 5.0 mg/kg/d X 14 days as induction treatment of patients with disseminated cryptococcosis and HIV.

Study Overview

• Status: Withdrawn
• Conditions: Invasive Cryptococcosis
• Intervention / Treatment: Drug: ABLC

Detailed Description

This is a randomized, open label, prospective study of ABLC at 5.0 and 10.0 mg/kg/d for treatment of patients with cryptococcal meningitis. Patients will be randomly assigned in a 1:1 ratio to receive 5.0 or 10.0 mg/kg/d of ABLC as induction therapy for cryptococcal meningitis. Patients receiving 10 mg/kg/d doses will be treated with ABLC for 7 days whereas patients receiving ABLC at 5.0 mg/kg/d will receive 14 days of ABLC therapy. After completion of induction therapy subjects will receive long-term fluconazole maintenance therapy at the discretion of the treating physician. The study will be conducted at the Washington Hospital Center

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of cryptococcal meningitis based on any of the following:

   • Cerebrospinal fluid positive for C. neoformans
   • Cerebrospinal fluid positive for cryptococcal antigen
2. Male or female 18 years of age or older.
3. All female patients must be non-lactating and have a negative serum pregnancy test at time of screening. Females of childbearing potential must be using a medically acceptable method of contraception and agree to continue its use during the study period, or must be one year postmenopausal, or have been surgically sterilized.
4. Willing and able to give a signed informed consent, or have a legally authorized representative who is willing or able to give consent

Exclusion Criteria:

1. A history or evidence of hypersensitivity to AmB or any of its metabolites.
2. A history or evidence of any psychiatric, neurological metabolic, or other chronic condition, which in the investigator's opinion, would make the patient unsuitable for the study or interfere with the evaluation of ABLC.
3. Inability to comply with the procedures of the study.
4. Patients who have received greater than 72 hours of therapy with another systemic antifungal agent within 2 weeks prior to enrollment

5. Patients with any of the following abnormal laboratory values

   • Baseline creatinine clearance of less than 50.
   • Bilirubin of greater than 5 times the upper limit of normal
   • AST or ALT of greater than 10 times the upper limit of normal
6. Life expectancy of less than 72 hours

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 5 mg/kg/d ABLC x 14 days; 5 mg/kg/d of Amphotericin B Lipid Complex for 14 days	Drug: ABLC
Experimental: 10/kg/kg/d x 7 days; 10 mg/kg/d of Amphotericin B Lipid Complex for 7 days	Drug: ABLC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Survival
Time to Sterilization of CSF

Secondary Outcome Measures

Outcome Measure
Infusion related and renal toxicity

Collaborators and Investigators

• Sponsor: Medstar Health Research Institute
• Collaborators: Enzon Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Shmuel Shoham, MD, Medstar Health Research Institute

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: April 24, 2007
• First Submitted That Met QC Criteria: August 2, 2012
• First Posted (Estimate): August 3, 2012

Study Record Updates

• Last Update Posted (Actual): February 17, 2021
• Last Update Submitted That Met QC Criteria: February 15, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: cryptococcosis; ABLC
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Cryptococcosis
• Other Study ID Numbers: 2006-273