Clinical trial NCT03505853: A Study to Investigate the Interaction Between Givosiran and a 5-probe Drug Cocktail in Patients With Acute Intermittent Porphyria (AIP)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Intermittent Porphyria (AIP)
Acute Hepatic Porphyria (AHP)
Porphyria, Acute Intermittent
Acute Porphyria
Keywords: RNAi therapeutic
Porphyria
Acute Hepatic Porphyria (AHP)
Acute Intermittent Porphyria (AIP)
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-04-23
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
timeFrame: Days 1 and 36
measure: Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
timeFrame: Days 1 and 36
Secondary outcomes:
measure: Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites
timeFrame: Days 1 and 36
measure: Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites
timeFrame: Days 1 and 36
measure: Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
timeFrame: Days 1 and 36
measure: Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
timeFrame: Days 1 and 36
measure: The pharmacodynamic (PD) effect of givosiran on urine levels of delta-aminolevulinic acid (ALA)
timeFrame: Days 1, 8, and 36
measure: The pharmacodynamic (PD) effect of givosiran on urine levels of Porphobilinogen (PBG) in patients with AIP
timeFrame: Days 1, 8, and 36
measure: Safety as evaluated by the proportion of subjects experiencing adverse events (AEs)
timeFrame: Day 1 - Day 92
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Nader Najafian, MD
role: STUDY_DIRECTOR
References: