Hepatic Cirrhosis, Hepatic Encephalopathy (HE)
Conditions
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.
Interventions
DRUGMNK6106
1 gram tablet of MNK6106 for oral administration
DRUGRifaximin
550 mg tablet of rifaximin for oral administration
Sponsors
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
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 1 instance of HE within 12 months 5. Has hyperammonaemia defined as ≥37 μmol/L 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ammonia Plasma Levels at Baseline and Day 5 | Baseline, Day 5 | This test measures the level of ammonia in your blood. Ammonia, also known as NH3, is a waste product made by your body during the digestion of protein. Normally, ammonia is processed in the liver, where it is changed into another waste product called urea. Urea is passed from the body in urine. If your body cannot process or eliminate ammonia, a lab test of a blood sample shows it has built up in the bloodstream. High ammonia levels in the blood can lead to serious health problems, including hepatic encephalopathy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events by the End of the Trial | within 15 days | End of trial is defined as 7 (+/-3) days after last study treatment |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
All 50 participants were enrolled in the United States and Puerto Rico
Participants by arm
| Arm | Count |
|---|---|
| Group A: MNK6106 2 Grams (Tid) Participants receive 2 (1 gm) tablets of MNK6106 three times daily (tid) for 5 days | 12 |
| Group B: MNK6106 4 Grams (Bid) Participants receive 4 (1 gm) tablets of MNK6106 twice daily (bid) for 5 days | 11 |
| Group C: MNK6106 4 Grams (Tid) Participants receive 4 (1 gm) tablets of MNK6106 tid for 5 days | 13 |
| Group D: Rifaximin 550 mg (Bid) Participants receive 1 (500 mg) tablet of rifaximin bid for 5 days | 12 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 |
| Overall Study | Randomized, but not treated due to Adverse Event | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Participant or Caregiver | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Group A: MNK6106 2 Grams (Tid) | Group C: MNK6106 4 Grams (Tid) | Group D: Rifaximin 550 mg (Bid) | Group B: MNK6106 4 Grams (Bid) |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants | 11 Participants | 10 Participants | 11 Participants | 10 Participants |
| Age, Continuous | 57.2 years STANDARD_DEVIATION 8.84 | 57.2 years STANDARD_DEVIATION 8.1 | 58.2 years STANDARD_DEVIATION 10.56 | 55.2 years STANDARD_DEVIATION 9.09 | 58.2 years STANDARD_DEVIATION 7.95 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 11 Participants | 7 Participants | 10 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 1 Participants | 6 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 43 Participants | 10 Participants | 11 Participants | 11 Participants | 11 Participants |
| Region of Enrollment United States | 48 participants | 12 participants | 13 participants | 12 participants | 11 participants |
| Sex: Female, Male Female | 20 Participants | 6 Participants | 5 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 28 Participants | 6 Participants | 8 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 | 0 / 13 | 0 / 12 |
| other Total, other adverse events | 5 / 12 | 6 / 11 | 8 / 13 | 5 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 | 2 / 13 | 0 / 12 |
Outcome results
Primary
Ammonia Plasma Levels at Baseline and Day 5
This test measures the level of ammonia in your blood. Ammonia, also known as NH3, is a waste product made by your body during the digestion of protein. Normally, ammonia is processed in the liver, where it is changed into another waste product called urea. Urea is passed from the body in urine. If your body cannot process or eliminate ammonia, a lab test of a blood sample shows it has built up in the bloodstream. High ammonia levels in the blood can lead to serious health problems, including hepatic encephalopathy.
Time frame: Baseline, Day 5
Population: modified Intent to Treat (mITT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: MNK6106 2 Grams (Tid) | Ammonia Plasma Levels at Baseline and Day 5 | Baseline | 70.4 μmol/L | Standard Deviation 23.4 |
| Group A: MNK6106 2 Grams (Tid) | Ammonia Plasma Levels at Baseline and Day 5 | Day 5/4 Hours Post Morning Dose | 69.8 μmol/L | Standard Deviation 27.7 |
| Group A: MNK6106 2 Grams (Tid) | Ammonia Plasma Levels at Baseline and Day 5 | Day 5/Pre-Dose in the Morning | 72.7 μmol/L | Standard Deviation 21.8 |
| Group B: MNK6106 4 Grams (Bid) | Ammonia Plasma Levels at Baseline and Day 5 | Baseline | 91.4 μmol/L | Standard Deviation 35 |
| Group B: MNK6106 4 Grams (Bid) | Ammonia Plasma Levels at Baseline and Day 5 | Day 5/4 Hours Post Morning Dose | 60.9 μmol/L | Standard Deviation 13.3 |
| Group B: MNK6106 4 Grams (Bid) | Ammonia Plasma Levels at Baseline and Day 5 | Day 5/Pre-Dose in the Morning | 63.9 μmol/L | Standard Deviation 16.9 |
| Group C: MNK6106 4 Grams (Tid) | Ammonia Plasma Levels at Baseline and Day 5 | Day 5/Pre-Dose in the Morning | 74.9 μmol/L | Standard Deviation 21.9 |
| Group C: MNK6106 4 Grams (Tid) | Ammonia Plasma Levels at Baseline and Day 5 | Baseline | 92.6 μmol/L | Standard Deviation 34.7 |
| Group C: MNK6106 4 Grams (Tid) | Ammonia Plasma Levels at Baseline and Day 5 | Day 5/4 Hours Post Morning Dose | 73.0 μmol/L | Standard Deviation 11.5 |
| Group D: Rifaximin 550 mg (Bid) | Ammonia Plasma Levels at Baseline and Day 5 | Baseline | 78.1 μmol/L | Standard Deviation 25 |
| Group D: Rifaximin 550 mg (Bid) | Ammonia Plasma Levels at Baseline and Day 5 | Day 5/4 Hours Post Morning Dose | 71.6 μmol/L | Standard Deviation 29.5 |
| Group D: Rifaximin 550 mg (Bid) | Ammonia Plasma Levels at Baseline and Day 5 | Day 5/Pre-Dose in the Morning | 75.8 μmol/L | Standard Deviation 31.3 |
Secondary
Number of Participants With Adverse Events by the End of the Trial
End of trial is defined as 7 (+/-3) days after last study treatment
Time frame: within 15 days
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: MNK6106 2 Grams (Tid) | Number of Participants With Adverse Events by the End of the Trial | Affected by Serious Adverse Events | 0 Participants |
| Group A: MNK6106 2 Grams (Tid) | Number of Participants With Adverse Events by the End of the Trial | Affected by Non-serious Adverse Events in the 5% Reporting Threshold | 5 Participants |
| Group A: MNK6106 2 Grams (Tid) | Number of Participants With Adverse Events by the End of the Trial | Affected by Any Non-serious Adverse Event | 5 Participants |
| Group B: MNK6106 4 Grams (Bid) | Number of Participants With Adverse Events by the End of the Trial | Affected by Serious Adverse Events | 0 Participants |
| Group B: MNK6106 4 Grams (Bid) | Number of Participants With Adverse Events by the End of the Trial | Affected by Non-serious Adverse Events in the 5% Reporting Threshold | 6 Participants |
| Group B: MNK6106 4 Grams (Bid) | Number of Participants With Adverse Events by the End of the Trial | Affected by Any Non-serious Adverse Event | 6 Participants |
| Group C: MNK6106 4 Grams (Tid) | Number of Participants With Adverse Events by the End of the Trial | Affected by Any Non-serious Adverse Event | 9 Participants |
| Group C: MNK6106 4 Grams (Tid) | Number of Participants With Adverse Events by the End of the Trial | Affected by Serious Adverse Events | 2 Participants |
| Group C: MNK6106 4 Grams (Tid) | Number of Participants With Adverse Events by the End of the Trial | Affected by Non-serious Adverse Events in the 5% Reporting Threshold | 8 Participants |
| Group D: Rifaximin 550 mg (Bid) | Number of Participants With Adverse Events by the End of the Trial | Affected by Serious Adverse Events | 0 Participants |
| Group D: Rifaximin 550 mg (Bid) | Number of Participants With Adverse Events by the End of the Trial | Affected by Non-serious Adverse Events in the 5% Reporting Threshold | 5 Participants |
| Group D: Rifaximin 550 mg (Bid) | Number of Participants With Adverse Events by the End of the Trial | Affected by Any Non-serious Adverse Event | 5 Participants |