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A Pharmacologically Guided Phase I/II Study of Daily Orally Administered Synthetic Hypericin in HIV-Infected Subjects
This study has been completed.
Sponsors and Collaborators: VIMRx Pharmaceuticals
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000792
  Purpose

To determine the safety and tolerance of daily oral hypericin when given to achieve target trough levels within defined cohorts. To determine the responses of surrogate markers of HIV infection to daily oral hypericin.

It is not known whether daily oral dosing will produce a tolerable prolonged exposure to therapeutic levels of hypericin. Pharmacokinetic modeling studies have demonstrated that daily oral dosing should produce a trough level in a desired range without excessive peak levels.


Condition Intervention Phase
HIV Infections
Drug: Hypericin
Phase I

MedlinePlus related topics: AIDS
Drug Information available for: Hypericin
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Pharmacokinetics Study
Official Title: A Pharmacologically Guided Phase I/II Study of Daily Orally Administered Synthetic Hypericin in HIV-Infected Subjects

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 24
Detailed Description:

It is not known whether daily oral dosing will produce a tolerable prolonged exposure to therapeutic levels of hypericin. Pharmacokinetic modeling studies have demonstrated that daily oral dosing should produce a trough level in a desired range without excessive peak levels.

Cohorts of six patients each receive escalating doses of oral hypericin daily. Blood is sampled for peak and trough levels the second week of therapy. A computer modeling algorithm will use these levels to determine the appropriate dose needed for each patient to achieve the desired trough level. When three of six patients at a given dose have completed 3 weeks of therapy without evidence of dose-limiting toxicity, data will be reviewed to determine whether subsequent patients should be entered at the next higher dose. The MTD is defined as the dose level immediately below that at which grade 3 or worse toxicity is seen in three or more of six patients.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Required:

  • PCP prophylaxis.

Allowed:

  • Rifabutin, ketoconazole, fluconazole, and acyclovir, provided the medication has been taken for at least 4 weeks prior to study entry without toxicity.
  • Topical medications such as clotrimazole troches or nystatin suspension.

Patients must have:

  • Documented HIV infection.
  • CD4 count <= 350 cells/mm3.
  • p24 antigen positive at >= 35 pcg/ml.
  • No active opportunistic infection at study entry that would require curative or suppressive therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Malignancy for which systemic chemotherapy is required.
  • Medically significant liver disease, orthostatic hypotension, hypertension, cardiac disease, seizure disorders, or lymphoma.
  • Any medical condition that would interfere with evaluation of the patient.

Concurrent Medication:

Excluded:

  • AZT, ddI, ddC, d4T, or any other antiretroviral medication.
  • Interferon or other immunomodulating drugs.
  • Cytotoxic chemotherapy.
  • Foscarnet.
  • Ganciclovir.
  • Antimycobacterial drugs other than rifabutin.
  • MAO inhibitors.
  • Hypertension-inducing, nephrotoxic, or hepatotoxic drugs.
  • Opiates.
  • Drugs known to cause photosensitivity.

Prior Medication:

Excluded within 1 month prior to study entry:

  • AZT, ddI, ddC, d4T, or any other antiretroviral medication.
  • Interferon or other immunomodulating drugs.
  • Cytotoxic chemotherapy.
  • Preparations known to contain hypericin.

Excluded within 3 months prior to study entry:

  • Ribavirin.
  • Hyperforate (500 mg tablets or ampules for IV injection) manufactured by Kline.
  • Psychotonin M Alcohol Extract manufactured by Steigerwald.
  • Hypericin (40 mg vial) by VIMRx.

Excluded within 14 days prior to study entry:

  • Foscarnet.
  • Ganciclovir.
  • Antimycobacterial drugs other than rifabutin.
  • MAO inhibitors.
  • Hypertension-inducing, nephrotoxic, or hepatotoxic drugs.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000792

Locations
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, United States, 02215
United States, New York
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Sponsors and Collaborators
VIMRx Pharmaceuticals
Investigators
Study Chair: Valentine FT
Study Chair: Crumpacker C
  More Information

Publications:
Study ID Numbers: ACTG 258
Study First Received: November 2, 1999
Last Updated: June 23, 2005
ClinicalTrials.gov Identifier: NCT00000792  
Health Authority: Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Administration, Oral
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents

Study placed in the following topic categories:
Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Hypericin
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
Anti-Infective Agents
RNA Virus Infections
Slow Virus Diseases
Immunologic Factors
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Psychotropic Drugs
Enzyme Inhibitors
Infection
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Lentivirus Infections
Central Nervous System Agents
Antidepressive Agents

ClinicalTrials.gov processed this record on January 15, 2009