A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of MNK6105 (an Intravenous Formulation of L-Ornithine Phenylacetate) in Hospitalized Patients With Cirrhosis and Hyperammonemia Associated With an Episode of Hepatic Encephalopathy
Trial Snapshot
- Phase
- Phase 3
- Status
- Withdrawn
- Sponsor
- Mallinckrodt
- Primary Endpoint
- Number of patients with a clinical response at Day 5
Study Overview
Brief Summary
This study is for patients with cirrhosis and hepatic encephalopathy who are in the hospital. This means they have a high ammonia level which is affecting their brain function.
All patients will receive the standard of (regular) care. Each will have an equal chance (like flipping a coin) of receiving the experimental drug or placebo along with the standard care.
Each patient will have tests during the first 24 hours, receive treatment for up to 5 days, and have 30 days of follow-up.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •To be included, a patient must:
- •Be the age of majority in their country (considered an adult)
- •Be male or non-pregnant, non-lactating female
- •Have OHE (Stage 2, 3, or 4) as a complication of cirrhosis
- •Have been hospitalized within 24 hours before start of infusion (SOI)
- •Receive at least 6 hours of SoC treatment
Exclusion Criteria
- •Patients will be excluded if they have inadequate renal function or any other disease, laboratory value, or condition (including allergy, drug use or treatments) that per protocol or in the opinion of the investigator, might increase the risk of compromising:
- •health or well-being of the patient
- •safety of study staff
- •analysis of results
Arms & Interventions
Placebo + SoC
Participants will receive SoC, along with continuous IV infusion of matching placebo for 5 days.
Intervention: Placebo (Drug)
Placebo + SoC
Participants will receive SoC, along with continuous IV infusion of matching placebo for 5 days.
Intervention: Standard of Care (Drug)
MNK6105 + SoC
Participants will receive standard of care (SoC), along with MNK-6105 delivered by continuous intravenous (IV) infusion as follows:
- Loading dose: 20 g infused over 6 hours
- Intermediate dose: 15 g infused over 18 hours
- Maintenance dose: 15 g infused over 24 hours for up to 4 days
Intervention: MNK-6105 (Drug)
MNK6105 + SoC
Participants will receive standard of care (SoC), along with MNK-6105 delivered by continuous intravenous (IV) infusion as follows:
- Loading dose: 20 g infused over 6 hours
- Intermediate dose: 15 g infused over 18 hours
- Maintenance dose: 15 g infused over 24 hours for up to 4 days
Intervention: Standard of Care (Drug)
Outcomes
Primary Outcomes
Number of patients with a clinical response at Day 5
Time Frame: at Day 5 (within 36 months)
Secondary Outcomes
- Number of patients discharged 30 days after end of treatment.(at Day 35 (within 36 months))
- Number of patients readmitted to the hospital due to overt hepatic encephalopathy (OHE) 30 days after discharge.(30 days after discharge (within 36 months))
- Number of patients with adverse events or deaths during the study(within 36 months)