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)

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03505853

Enrollment

Registered

2018-04-23

Start date

2018-04-26

Completion date

2019-01-10

Last updated

2019-03-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

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

Brief summary

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.

Interventions

DRUGGivosiran

single dose of givosiran by subcutaneous (sc) injection

DRUG5-probe cocktail

includes midazolam, caffeine, losartan, omeprazole, and dextromethorphan

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail	Days 1 and 36	Area under the concentration-time curve (AUC)

Secondary

Measure	Time frame	Description
The pharmacodynamic (PD) effect of givosiran on urine levels of delta-aminolevulinic acid (ALA)	Days 1, 8, and 36	—
The pharmacodynamic (PD) effect of givosiran on urine levels of Porphobilinogen (PBG) in patients with AIP	Days 1, 8, and 36	—
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites	Days 1 and 36	Area under the concentration-time curve (AUC)
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail	Days 1 and 36	Terminal half-life (t1/2)
Safety as evaluated by the proportion of subjects experiencing adverse events (AEs)	Day 1 - Day 92	—

Countries

Sweden

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026