Studies in Porphyria III: Heme and Tin Mesoporphyrin in Acute Porphyrias

PROTOCOL OUTLINE: This is an unblinded, dose ranging study. Patients receive heme arginate alone or in combination with tin mesoporphyrin.

Patients receive tin mesoporphyrin IV as a single dose. Heme arginate is administered as a single intravenous infusion.

Patients are entered in cohorts of 4. Subsequent cohorts of 4 patients each receive escalating doses of tin mesoporphyrin in combination with 1 of 2 different dosages of heme arginate. Subjects must maintain a constant diet.

Patients experiencing adverse reactions are followed as clinically indicated.

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Documented acute intermittent porphyria in remission for at least 1 month
• Increased excretion of porphyrin precursors
• Absence of neurovisceral symptoms due to porphyria for at least 1 month

--Prior/Concurrent Therapy--

• At least 1 month since prior heme preparation therapy
• Concurrent medication for coexisting condition is allowed, as long as dose and pattern of administration is held constant during study

--Patient Characteristics--

• Renal: Urinary porphobilinogen excretion of at least 20 mg every 24 hours
• Other: Not pregnant Fertile female patients must use effective contraception during and at least 6 months before study At least 1 month since any symptoms of disease No concurrent acute hemorrhagic disorder such as: Gastrointestinal bleeding Intracerebral hemorrhage No known hypersensitivity to heme arginate, tin mesoporphyrin, another heme preparation, or related heme analogue No other condition that may increase risk to patient