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Completed

NCT Number: NCT03505853

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

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.

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Key information

Conditions

Acute Intermittent Porphyria (AIP) Acute Hepatic Porphyria (AHP) Acute Porphyria Congenital, Hereditary, and Neonatal Diseases and Abnormalities Coproporphyria, Hereditary Digestive System Diseases Genetic Diseases, Inborn Liver Diseases Metabolic Diseases Nutritional and Metabolic Diseases Porphyria, Acute Intermittent Porphyrias Porphyrias, Hepatic Skin Diseases Skin Diseases, Genetic Skin and Connective Tissue Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Clinical Trial Site

Stockholm, Sweden

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Givosiran

Drug

single dose of givosiran by subcutaneous (sc) injection

5-probe cocktail

Drug

includes midazolam, caffeine, losartan, omeprazole, and dextromethorphan

Primary outcomes

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

    Time frame: Days 1 and 36

    Area under the concentration-time curve (AUC)

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

    Time frame: Days 1 and 36

    Maximum plasma concentration (Cmax)

Secondary outcomes

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

    Time frame: Days 1 and 36

    Area under the concentration-time curve (AUC)

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

    Time frame: Days 1 and 36

    Maximum plasma concentration (Cmax)

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

    Time frame: Days 1 and 36

    Terminal half-life (t1/2)

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

    Time frame: Days 1 and 36

    Volume of distribution (V/F)

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

    Time frame: Days 1, 8, and 36

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

    Time frame: Days 1, 8, and 36

  7. Safety as evaluated by the proportion of subjects experiencing adverse events (AEs)

    Time frame: Day 1 - Day 92

Sponsors and collaborators

Lead sponsor

Alnylam Pharmaceuticals

Industry

Registry information

Official study 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)

Important dates

Study start
2018
Primary completion
2018
Study completion
2019
First posted
Apr 23, 2018
Registry last updated
Mar 12, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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