A Pharmacologically Guided Phase I/II Study of Daily Orally Administered Synthetic Hypericin in HIV-Infected Subjects

October 27, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Adult AIDS CRS
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess - East Campus A0102 CRS
    • New York
      • New York, New York, United States, 10016
        • NY Univ. HIV/AIDS CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

VIMRx Pharmaceuticals

Investigators

  • Study Chair: Crumpacker C

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

January 1, 1995

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

November 4, 2021

Last Update Submitted That Met QC Criteria

October 27, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 258
  • 11235 (Registry Identifier: DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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