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

NCT ID: NCT00000792

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 1995-01-31

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.

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.

Conditions

HIV Infections

Keywords

Administration, Oral; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Antiviral Agents

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Hypericin

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VIMRx Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Valentine FT

Role: STUDY_CHAIR

Crumpacker C

Role: STUDY_CHAIR

Locations

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

Beth Israel Deaconess - East Campus A0102 CRS

Boston, Massachusetts, United States

NY Univ. HIV/AIDS CRS

New York, New York, United States

Countries

United States

References

Furner V, Bek M, Gold J. A Phase I/II unblinded dose ranging study of hypericin in HIV-positive subjects. Int Conf AIDS. 1991 Jun 16-21;7(2):199 (abstract no WB2071)

Reference Type: BACKGROUND

Gulick RM, McAuliffe V, Holden-Wiltse J, Crumpacker C, Liebes L, Stein DS, Meehan P, Hussey S, Forcht J, Valentine FT. Phase I studies of hypericin, the active compound in St. John's Wort, as an antiretroviral agent in HIV-infected adults. AIDS Clinical Trials Group Protocols 150 and 258. Ann Intern Med. 1999 Mar 16;130(6):510-4. doi: 10.7326/0003-4819-130-6-199903160-00015.

Reference Type: BACKGROUND

PMID: 10075619 (View on PubMed)

Other Identifiers

11235

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 258

Identifier Type: -

Identifier Source: org_study_id