First Patient Enrolled in Hepatic Cirrhosis and Chronic Hepatic Encephalopathy Study

Mallinckrodt confirmed enrollment of the first patient in the company's Phase 2a study assessing the pharmacokinetics, pharmacodynamics and safety of the oral investigational drug MNK-6106 (L-ornithine phenylacetate) versus rifaximin in patients with hepatic (liver) cirrhosis and hepatic encephalopathy (HE). Study completion is expected by first quarter 2020.

Mallinckrodt acquired MNK-6106 and the intravenous investigational drug MNK-6105 (L-ornithine phenylacetate) when it completed the acquisition of Ocera Therapeutics in December 2017. MNK-6106 is being evaluated for post-discharge continuity of care for patients with cirrhosis and, if approved, may have the potential to reduce the risk of recurrent HE episodes and possibly rehospitalization.

The company expects to begin recruiting by the end of 2019 for a Phase 3 clinical trial investigating MNK-6105 in patients being treated for acute HE in the hospital.

"Enrollment of the first patient in this clinical trial of investigational drug MNK-6106 marks another important milestone in the compound's development program," said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer at Mallinckrodt. "The evaluation of the oral formulation will allow us to gain insights into the potential utility of this compound to manage patients whose acute episode of HE has resolved, and who may require longer-term treatment to reduce the likelihood of future episodes and potential complications."

The clinical study is titled "A Phase 2a Comparator, Randomized, Open-Label Study to Assess the Pharmacodynamics, Safety and Pharmacokinetics of Oral Administration MNK-6106 (L-ornithine Phenylacetate) vs. Rifaximin in Subjects with Hepatic Cirrhosis and a History of Prior Episodes of Hepatic Encephalopathy." The study will include adult men and non-pregnant women with hepatic cirrhosis who have a history of at least two or more documented episodes of HE in the last 12 months – with one in the last six months – and who present with hyperammonemia at the time of screening.

Approximately 48 subjects who meet eligibility criteria will be randomly assigned to one of four groups. Those in three experimental arms will receive MNK-6106 for five days with food, according to different dosing regimens – 2 grams, three times daily; 4 grams, twice daily; and 4 grams, three times daily. The fourth group, the active comparator group, will receive 550 milligrams of rifaximin twice daily for five days with food.

The primary objective of this study is to evaluate the pharmacological effect of this compound through the assessment of plasma ammonia concentration as a pharmacodynamic marker following oral administrations of MNK-6106 with rifaximin as a control in participants with hepatic cirrhosis and a history of prior episodes of HE. The study's endpoints are the absolute and percentage change in plasma ammonia from baseline, in a timeframe from baseline to five days.

MNK-6106 (L-ornithine phenylacetate), an ammonia scavenger, is being studied for treatment of hepatic encephalopathy, a neuropsychiatric syndrome associated with hyperammonemia, a complication of chronic liver disease.

Hepatic encephalopathy is a critical neurocognitive complication of chronic liver disease. It is associated with elevated circulating ammonia levels stemming from end stage liver disease (cirrhosis). Symptoms range from mildly altered mental status to coma or death. Severe hepatic encephalopathy in patients with cirrhosis is associated with a mortality of more than 50% in the first year alone. Once a patient suffers an acute hepatic encephalopathy episode, prevention of recurrence is critical and may require chronic therapy.

-----------------------------------------------------------------------
Editor's Note:

If you have any suggestion to the content, 

please email: Julia.Zhang@ubmsinoexpo.com