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

Alnylam Pharmaceuticals10 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Intermittent Porphyria (AIP)Acute Hepatic Porphyria (AHP)Porphyria, Acute Intermittent Acute Porphyria

Interventions

GivosiranDRUG

single dose of givosiran by subcutaneous (sc) injection

5-probe cocktailDRUG

includes midazolam, caffeine, losartan, omeprazole, and dextromethorphan

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (1)

Clinical Trial Site

Stockholm, Sweden

Outcomes

Primary Outcomes

Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail

Area under the concentration-time curve (AUC)

Time frame: Days 1 and 36

Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail

Maximum plasma concentration (Cmax)

Time frame: Days 1 and 36

Secondary Outcomes

Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites

Area under the concentration-time curve (AUC)

Time frame: Days 1 and 36

Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites

Maximum plasma concentration (Cmax)

Time frame: Days 1 and 36

Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail

Terminal half-life (t1/2)

Time frame: Days 1 and 36

Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail

Volume of distribution (V/F)

Time frame: Days 1 and 36

The pharmacodynamic (PD) effect of givosiran on urine levels of delta-aminolevulinic acid (ALA)

Time frame: Days 1, 8, and 36

The pharmacodynamic (PD) effect of givosiran on urine levels of Porphobilinogen (PBG) in patients with AIP

Time frame: Days 1, 8, and 36

Data from ClinicalTrials.gov

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