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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Givosiran with 5-probe cocktail | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Givosiran | Drug | single dose of givosiran by subcutaneous (sc) injection |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites | Area under the concentration-time curve (AUC) | Days 1 and 36 |
| Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nader Najafian, MD | Alnylam Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Stockholm | Sweden |
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| 5-probe cocktail |
| Drug |
includes midazolam, caffeine, losartan, omeprazole, and dextromethorphan |
|
Maximum plasma concentration (Cmax)
| Days 1 and 36 |
| Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail | Terminal half-life (t1/2) | Days 1 and 36 |
| Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail | Volume of distribution (V/F) | Days 1 and 36 |
| The pharmacodynamic (PD) effect of givosiran on urine levels of delta-aminolevulinic acid (ALA) | Days 1, 8, and 36 |
| The pharmacodynamic (PD) effect of givosiran on urine levels of Porphobilinogen (PBG) in patients with AIP | Days 1, 8, and 36 |
| Safety as evaluated by the proportion of subjects experiencing adverse events (AEs) | Day 1 - Day 92 |
| ID | Term |
|---|---|
| D017118 | Porphyria, Acute Intermittent |
| D046349 | Coproporphyria, Hereditary |
| D011164 | Porphyrias |
| ID | Term |
|---|---|
| D017094 | Porphyrias, Hepatic |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C000630124 | givosiran |
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