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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000792

Collaborator

VIMRx Pharmaceuticals (Industry)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Hypericin	Phase 1

Detailed Description

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 Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Completion Date :

Jan 1, 1995

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
2	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts	United States	02215
3	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016