A Study to Investigate the Interaction Between Givosiran and a 5-probe Drug Cocktail in Patients With Acute Intermittent Porphyria (AIP)

A Drug-Drug Interaction Study to Investigate the Effect of Givosiran on the Pharmacokinetics (PK) of Midazolam, Caffeine, Losartan, Omeprazole, and Dextromethorphan in Patients With Acute Intermittent Porphyria (AIP) Who Are Asymptomatic High Excreters (ASHE)

The purpose of this study is to evaluate the effect of givosiran on the pharmacokinetics of the 5-probe cocktail of midazolam, caffeine, losartan, omeprazole, and dextromethorphan, and their metabolites, in asymptomatic patients with Acute Intermittent Porphyria.

Inclusion Criteria:

• 18 to 65 years old
• Weight between 45kg and 110kg, inclusive, if male
• Weight between 45kg and 100 kg, inclusive, if female
• Diagnosis of acute intermittent porphyria (AIP)
• Elevated urine PBG level
• Not be pregnant or breast feeding, and must be willing to use a highly effective method of contraception

Exclusion Criteria:

• Clinically significant abnormal laboratory results
• Experienced an acute porphyria attack within past 12 months
• History of multiple drug allergies, intolerances or sensitivities
• History of recurrent pancreatitis
• Received an experimental drug, within 3 months of dosing
• Donated or lost an excessive amount of blood within 60 days of dosing