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

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ClinicalTrials.gov Identifier: NCT03505853
Recruitment Status : Recruiting
First Posted : April 23, 2018
Last Update Posted : June 21, 2018
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Acute Intermittent Porphyria (AIP) Acute Hepatic Porphyria (AHP) Porphyria, Acute Intermittent Acute Porphyria Drug: Givosiran Drug: 5-probe cocktail Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : April 26, 2018
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : October 2018


Arm Intervention/treatment
Experimental: Givosiran with 5-probe cocktail Drug: Givosiran
single dose of givosiran by subcutaneous (sc) injection

Drug: 5-probe cocktail
includes midazolam, caffeine, losartan, omeprazole, and dextromethorphan




Primary Outcome Measures :
  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 Outcome Measures :
  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 ]


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03505853


Contacts
Contact: Alnylam Clinical Trials Information Line 617-575-7400 clinicaltrials@alnylam.com
Contact: Alnylam Clinical Trials Information Line 1-866-330-0326

Locations
Sweden
Clinical Trial Site Recruiting
Stockholm, Sweden
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
Study Director: Nader Najafian, MD Alnylam Pharmaceuticals

Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03505853     History of Changes
Other Study ID Numbers: ALN-AS1-004
First Posted: April 23, 2018    Key Record Dates
Last Update Posted: June 21, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alnylam Pharmaceuticals:
RNAi therapeutic
Porphyria
Acute Hepatic Porphyria (AHP)
Acute Intermittent Porphyria (AIP)

Additional relevant MeSH terms:
Omeprazole
Porphyrias
Porphyria, Erythropoietic
Porphyria, Acute Intermittent
Porphyrias, Hepatic
Coproporphyria, Hereditary
Metabolic Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Liver Diseases
Digestive System Diseases
Dextromethorphan
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antitussive Agents
Respiratory System Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Physiological Effects of Drugs