Clinical trial NCT00000964: The Effect of Stomach Acid on Foscarnet
Official title: The Effect of Increasing Gastric pH Upon the Bioavailability of Orally Administered Phosphonoformic Acid (Foscarnet)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Ranitidine
Phosphorus Acids
Drug Evaluation
Acquired Immunodeficiency Syndrome
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To see if ranitidine, by reducing stomach acidity, can enhance the effectiveness of foscarnet, by making foscarnet more available to the body.

Foscarnet is an antiviral compound. Laboratory studies have shown it to be active against HIV. However, only 12 - 22 percent of an oral foscarnet dose is absorbed by the body. Ranitidine suppresses gastric acid output, increasing gastric pH. Thus by increasing gastric pH (decreasing stomach acidity), less foscarnet is expected to be decomposed or broken down in the stomach. Thus, more foscarnet should be absorbed into the body.

Detailed description: Foscarnet is an antiviral compound. Laboratory studies have shown it to be active against HIV. However, only 12 - 22 percent of an oral foscarnet dose is absorbed by the body. Ranitidine suppresses gastric acid output, increasing gastric pH. Thus by increasing gastric pH (decreasing stomach acidity), less foscarnet is expected to be decomposed or broken down in the stomach. Thus, more foscarnet should be absorbed into the body.

Six asymptomatic HIV-infected males, or those with limited symptoms of early AIDS-related complex ( ARC ), will receive one dose intravenously of ranitidine in distilled water and one dose of placebo (distilled water alone), followed in 1 hour by foscarnet in oral solution. The order of ranitidine and placebo is randomized and the two foscarnet doses are separated by at least 72 hours. A nasogastric pH probe is placed on each morning of drug administration to monitor gastric pH.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Acetaminophen and sedatives.

Patient must be able to give informed consent.

Exclusion Criteria

Patients with the following are excluded:

* Unintentional weight loss in excess of 10 pounds or 10 percent of usual body weight within 2 years prior to study.
* Unexplained temperature above 38 degrees Celsius on more than 5 consecutive days or on more than 10 days in any 30 days in 2 years prior to expected study entry.
* Unexplained diarrhea defined by two or more stools/day for at least 14 days during a 120-day interval.

Prior Medication:

Excluded within 1 week of entry into study:

* Probenecid, aspirin, or diuretics.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Adult AIDS CRS
state: Maryland
Study officials:
name: DM Kornhauser
role: STUDY_CHAIR
References:
citation: Barditch-Crovo PA, Petty BG, Gambertoglio J, Nerhood LJ, Kuwahara S, Hafner R, Lietman PS, Kornhauser DM. The effect of increasing gastric pH upon the bioavailability of orally-administered foscarnet. Antiviral Res. 1998 Jun;38(3):209-12. doi: 10.1016/s0166-3542(98)00024-2.