NCT03505853

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Apr 2018

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 13, 2018

Completed
10 days until next milestone

First Posted

Study publicly available on registry

April 23, 2018

Completed
3 days until next milestone

Study Start

First participant enrolled

April 26, 2018

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 16, 2018

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 10, 2019

Completed
Last Updated

March 12, 2019

Status Verified

March 1, 2019

Enrollment Period

7 months

First QC Date

April 13, 2018

Last Update Submit

March 10, 2019

Conditions

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

Keywords

RNAi therapeuticPorphyriaAcute Hepatic Porphyria (AHP)Acute Intermittent Porphyria (AIP)

Outcome Measures

Primary Outcomes (2)

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

    Area under the concentration-time curve (AUC)

    Days 1 and 36

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

    Maximum plasma concentration (Cmax)

    Days 1 and 36

Secondary Outcomes (7)

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

    Days 1 and 36

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

    Days 1 and 36

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

    Days 1 and 36

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

    Days 1 and 36

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

    Days 1, 8, and 36

  • +2 more secondary outcomes

Study Arms (1)

Givosiran with 5-probe cocktail

EXPERIMENTAL
Drug: GivosiranDrug: 5-probe cocktail

Interventions

GivosiranDRUG

single dose of givosiran by subcutaneous (sc) injection

Givosiran with 5-probe cocktail
5-probe cocktailDRUG

includes midazolam, caffeine, losartan, omeprazole, and dextromethorphan

Givosiran with 5-probe cocktail

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Clinical Trial Site

Stockholm, Sweden

Location

MeSH Terms

Conditions

Porphyria, Acute IntermittentCoproporphyria, HereditaryPorphyrias

Interventions

givosiran

Condition Hierarchy (Ancestors)

Porphyrias, HepaticLiver DiseasesDigestive System DiseasesSkin Diseases, GeneticGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesSkin DiseasesSkin and Connective Tissue DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • Nader Najafian, MD

    Alnylam Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 13, 2018

First Posted

April 23, 2018

Study Start

April 26, 2018

Primary Completion

November 16, 2018

Study Completion

January 10, 2019

Last Updated

March 12, 2019

Record last verified: 2019-03

Locations

SE(1)