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MNK6106 for Liver Disease (Hepatic Cirrhosis) That in the Past Has Affected the Brain (Hepatic Encephalopathy)

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ClinicalTrials.gov Identifier: NCT03712280
Recruitment Status : Recruiting
First Posted : October 19, 2018
Last Update Posted : August 7, 2019
Sponsor:
Information provided by (Responsible Party):
Mallinckrodt

Tracking Information
First Submitted Date  ICMJE October 16, 2018
First Posted Date  ICMJE October 19, 2018
Last Update Posted Date August 7, 2019
Actual Study Start Date  ICMJE December 1, 2018
Estimated Primary Completion Date October 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 2, 2019)
Area under the plasma concentration-time curve (AUC0-24) for ammonia [ Time Frame: within 24 hours post-dose ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 17, 2018)
Percentage change of plasma ammonia (AMM) from baseline. [ Time Frame: Baseline to 5 days ]
To evaluate the pharmacological activities through plasma AMM concentration as a PD marker following oral administrations of MNK6106 with rifaximin as a control in subjects with hepatic cirrhosis and a history of prior episodes of HE.
Change History Complete list of historical versions of study NCT03712280 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2019)
  • Number of participants with adverse events by the end of the trial [ Time Frame: within 10 days ]
  • Maximum plasma concentration (Cmax) of phenylacetic acid [ Time Frame: within 5 days ]
  • Number of participants with symptoms of high levels of ammonia in the blood (hyperammonemic crisis) [ Time Frame: within 5 days ]
  • Mean phenylacetylglutamine (PAGN) excreted in urine within 24 hours post-dose [ Time Frame: within 24 hours post-dose ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2018)
  • Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Final Visit (7 days postdosing) (+ 3 day window) ]
    An AE is any untoward or undesirable medical occurrence in a subject who is administered a study treatment, which does not necessarily have to have a causal relationship with this treatment. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 5 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
  • Phenylacetic Acid (PAA) Cmax exposure and neurotoxicity [ Time Frame: Baseline to 5 days ]
    Relationship between plasma peak PAA level and the incidence of nervous system AEs
  • Number and severity of symptomatic hyperammonemic crises and correlation between 24-h urinary PAGN excretion (U-PAGN0-24) and plasma ammonia (AMM) AUC0-24. [ Time Frame: Baseline to 5 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MNK6106 for Liver Disease (Hepatic Cirrhosis) That in the Past Has Affected the Brain (Hepatic Encephalopathy)
Official Title  ICMJE A Randomized, Open-Label, Phase 2a Comparator Study to Assess the Pharmacodynamics, Safety and Pharmacokinetics of Oral Administration MNK6106 (L-Ornithine Phenylacetate) Versus Rifaximin in Subjects With Hepatic Cirrhosis and a History of Prior Episodes of Hepatic Encephalopathy
Brief Summary

The main reason for this study is to see how the study drug interacts with the body.

It will compare different doses of the study drug with a drug already in use.

Participants will be adults with liver disease that has affected the brain in the past.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatic Cirrhosis
  • Hepatic Encephalopathy (HE)
Intervention  ICMJE
  • Drug: MNK6106
    1 gram tablet of MNK6106 for oral administration
    Other Name: Study Drug
  • Drug: Rifaximin
    550 mg tablet of rifaximin for oral administration
    Other Name: Xifaxan
Study Arms  ICMJE
  • Experimental: Group A: MNK6106 2 grams (tid)
    Participants receive 2 tablets of MNK6106 three times daily (tid) for 5 days
    Intervention: Drug: MNK6106
  • Experimental: Group B: MNK6106 4 grams (bid)
    Participants receive 4 tablets of MNK6106 twice daily (bid) for 5 days
    Intervention: Drug: MNK6106
  • Experimental: Group C: MNK6106 4 grams (tid)
    Participants receive 4 tablets of MNK6106 tid for 5 days
    Intervention: Drug: MNK6106
  • Active Comparator: Group D: Rifaximin 550 mg (bid)
    Participants receive 1 tablet of rifaximin bid for 5 days
    Intervention: Drug: Rifaximin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 17, 2018)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 30, 2019
Estimated Primary Completion Date October 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

A potential participant may only be included if (at screening), he/she:

  1. Understands the study and has signed informed consent
  2. Is an adult, not pregnant or lactating
  3. Has cirrhosis of the liver
  4. Has had 2 instances of HE within 12 months (1 within the last 6)
  5. Has hyperammonaemia at screening

Key Exclusion Criteria:

A potential participant will be excluded if (at screening), he/she:

  1. Has contraindicated allergies
  2. Expects liver transplant within 1 month
  3. Has had a liver shunt within the last 3 months
  4. Has inadequate kidney, gastrointestinal, or cardiac function
  5. Has cancer, infection, lab abnormalities, or any other condition that, per protocol or in the opinion of the investigator might compromise:

    1. the safety and well-being of the participant or potential offspring
    2. the safety of study staff
    3. the analysis of results
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: For questions about participating 800-556-3314 clinicaltrials@mnk.com
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03712280
Other Study ID Numbers  ICMJE MNK61062107
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mallinckrodt
Study Sponsor  ICMJE Mallinckrodt
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Team Leader Mallinckrodt
PRS Account Mallinckrodt
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP