Pharmacokinetics Of Emulsified Avacopan In ANCA-associated Vasculitis With Severe Diffuse Alveolar Hemorrhage
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Mayo Clinic
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Change in Avacopan blood level over time
Study Overview
Brief Summary
The purpose of this study is to determine the 72-hour pharmacokinetics of emulsified avacopan at a dose of 30 mg twice daily given to up to 6 patients with active severe GPA or MPA with diffuse alveolar hemorrhage (DAH) requiring mechanical ventilation for respiratory support.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Fulfillment of the definitions of the Second Chapel Hill Consensus Conference for ANCA-associated vasculitis (either granulomatosis with polyangiitis (GPA) or microscopic polyangiitis MPA).
- •Positivity for ANCA, directed against PR3 or MPO.
- •Diffuse alveolar hemorrhage.
- •Respiratory failure requiring mechanical ventilation.
- •Severe newly diagnosed disease or severe relapsing disease. Severe new or relapsing disease is defined as at least one major BVAS/WG item or a score ≥ 3 and the investigator deems standard treatment for severe disease is necessary.
- •Minimum BVAS-WG of
- •Requirement of standard-of-care remission induction therapy for active severe ANCA-associated vasculitis (GPA or MPA).
Exclusion Criteria
- •Diagnosis with eosinophilic granulomatosis with polyangiitis (EGPA, formally Churg-Strauss syndrome) as defined by the Chapel Hill consensus conference.
- •Allergies: History of severe allergic reaction to avacopan
- •History of documented anti-glomerular basement membrane disease (anti-GBM disease)
- •Previous administration of avacopan within the last 5 days.
- •Concomitant use of a strong CYP3A4 inhibitor.
- •Aspartate aminotransferase [AST], alanine amino transferase [ALT], alkaline phosphatase, or total bilirubin elevation >2.5 times the upper limit of normal (unless attributed to vasculitis) on routine liver function testing obtained within 3 days prior to anticipated treatment with avacopan.
- •Evidence of prior active or current Hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency (HIV) infection.
- •Active serious infection, including localized infection.
- •Pregnancy and breastfeeding
Arms & Interventions
Avacopan
Subjects will receive solubilized avacopan at a dose of 30 mg twice daily for 3 consecutive days, applied via NG tube.
Intervention: Avacopan (Drug)
Outcomes
Primary Outcomes
Change in Avacopan blood level over time
Time Frame: 72 hours
The primary objective of this study is to determine the blood (serum) level changes of Avacopan over time (pharmacokinetics) when Avacopan capsules are solubilized in heated water and administered to patients with Diffuse Alveolar Hemorrhage (DAH) due to GPA or MPA via nasogastric tube. Blood will be drawn pre-dose, post-dose 30 minutes, 1-hour, 2-hour, 4-hour, and 6-hour for the first dose and pre-dose for the remaining 72 hours and stored for analysis.
Secondary Outcomes
- Measure in Markers of Neutrophil Activation on Serum Samples(72 hours)
Investigators
Ulrich Specks, MD
Principal Investigator
Mayo Clinic