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

Acute Intermittent Porphyria (AIP) Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03505853
• Other study ID #: ALN-AS1-004
• Status: Completed
• Phase: Phase 1
• Start date: April 26, 2018
• Est. completion date: January 10, 2019

Study information

• Verified date: March 2019
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 10, 2019
• Est. primary completion date: November 16, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Hepatic Porphyria (AHP)
• Acute Intermittent Porphyria (AIP)
• Acute Porphyria
• Porphyria, Acute Intermittent
• Porphyria, Erythropoietic
• Porphyrias

Intervention

Drug:
• Givosiran
single dose of givosiran by subcutaneous (sc) injection
• 5-probe cocktail
includes midazolam, caffeine, losartan, omeprazole, and dextromethorphan

Locations

Country	Name	City	State
Sweden	Clinical Trial Site	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Country where clinical trial is conducted

Sweden, 

Outcome

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