Back to resultsA Study to Investigate the Interaction Between Givosiran and a 5-probe Drug Cocktail in Patients With Acute Intermittent Porphyria (AIP)
Primary Purpose
Acute Intermittent Porphyria (AIP), Acute Hepatic Porphyria (AHP), Porphyria, Acute Intermittent
Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
Givosiran
5-probe cocktail
Sponsored by
About this trial
This is an interventional treatment trial for Acute Intermittent Porphyria (AIP) focused on measuring RNAi therapeutic, Porphyria, Acute Hepatic Porphyria (AHP), Acute Intermittent Porphyria (AIP)
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
Sites / Locations
- Clinical Trial Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Givosiran with 5-probe cocktail
Arm Description
Outcomes
Primary Outcome Measures
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Area under the concentration-time curve (AUC)
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Maximum plasma concentration (Cmax)
Secondary Outcome Measures
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites
Area under the concentration-time curve (AUC)
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites
Maximum plasma concentration (Cmax)
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Terminal half-life (t1/2)
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Volume of distribution (V/F)
The pharmacodynamic (PD) effect of givosiran on urine levels of delta-aminolevulinic acid (ALA)
The pharmacodynamic (PD) effect of givosiran on urine levels of Porphobilinogen (PBG) in patients with AIP
Safety as evaluated by the proportion of subjects experiencing adverse events (AEs)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03505853
Brief Title
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
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
April 26, 2018 (Actual)
Primary Completion Date
November 16, 2018 (Actual)
Study Completion Date
January 10, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alnylam Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Givosiran with 5-probe cocktail
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Givosiran
Intervention Description
single dose of givosiran by subcutaneous (sc) injection
Intervention Type
Drug
Intervention Name(s)
5-probe cocktail
Intervention Description
includes midazolam, caffeine, losartan, omeprazole, and dextromethorphan
Primary Outcome Measure Information:
Title
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Description
Area under the concentration-time curve (AUC)
Time Frame
Days 1 and 36
Title
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Description
Maximum plasma concentration (Cmax)
Time Frame
Days 1 and 36
Secondary Outcome Measure Information:
Title
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites
Description
Area under the concentration-time curve (AUC)
Time Frame
Days 1 and 36
Title
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites
Description
Maximum plasma concentration (Cmax)
Time Frame
Days 1 and 36
Title
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Description
Terminal half-life (t1/2)
Time Frame
Days 1 and 36
Title
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Description
Volume of distribution (V/F)
Time Frame
Days 1 and 36
Title
The pharmacodynamic (PD) effect of givosiran on urine levels of delta-aminolevulinic acid (ALA)
Time Frame
Days 1, 8, and 36
Title
The pharmacodynamic (PD) effect of givosiran on urine levels of Porphobilinogen (PBG) in patients with AIP
Time Frame
Days 1, 8, and 36
Title
Safety as evaluated by the proportion of subjects experiencing adverse events (AEs)
Time Frame
Day 1 - Day 92
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nader Najafian, MD
Organizational Affiliation
Alnylam Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Trial Site
City
Stockholm
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
A Study to Investigate the Interaction Between Givosiran and a 5-probe Drug Cocktail in Patients With Acute Intermittent Porphyria (AIP)
We'll reach out to this number within 24 hrs