Ascites Hepatic, Cirrhosis, Liver, Liver Fibrosis
Conditions
Keywords
Terlipressin, Cirrhosis, Vasoconstrictor, Refractory Ascites
Brief summary
This 2-part study will evaluate PHIN-214 given as a single one-time dose (Part 1) and in multiple doses (given as daily doses for 28-days) (in Part 2). Specifically, this study evaluates PHIN-214, to determine the safety, tolerability, and pharmacokinetic effects of PHIN-214, and to establish the maximum tolerated dose or optimal beneficial dose in patients with Child Pugh A and B Cirrhosis.
Detailed description
PHIN-214 action has similar actions as another medication called terlipressin or TERLIVAZ®. Terlipressin has been shown to reduce portal hypertension, improve renal function, and induce natriuresis in cirrhotic patients with ascites without hepatorenal syndrome (HRS). It is approved in several countries including the US for the treatment of bleeding esophageal varices and HRS type 1 and is usually administered using multiple IV doses given by bolus injections in the hospital. This study is an open label, first in human study of PHIN-214. PHIN-214 is a terlipressin derivative administered subcutaneously. It is a partial V1a agonist which is designed to reduce splanchnic blood pooling and portal hypertension. A resultant increase in systemic pressure and renal arterial pressure may increase kidney perfusion and creatinine clearance. This study will evaluate a single dose of PHIN-214 (in Part 1) and in Part 2, daily doses of PHIN-214 for up to 28-days (called multiple ascending doses) of PHIN-214 to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of PHIN-214 in subjects with advanced cirrhosis.
Interventions
DRUGPHIN-214 Subcutaneous injection
subcutaneous injection(s) with PHIN-214 terlipressin derivative
Sponsors
PharmaIN
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. History of cirrhosis based on histology or a combination of clinical, radiological, or biochemical assessment and classified as Child-Pugh A or B 2. Participants may be male or female aged 18 to 75 years. 3. Body mass index (BMI) within the range 18 to 40 kg/m2 (inclusive) at screening. 4. Female participants must be non-pregnant, non-lactating, or of non-childbearing potential or using highly efficient contraception for the full duration of the study Key
Exclusion criteria
1. Significant abnormalities in medical history or on physical examination, including: respiratory disease requiring therapy or history of respiratory failure, cardiovascular disease or hypertension, electrocardiogram abnormalities or history of significant EKG abnormalities. 2. History of diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, or any other disorder associated with fluid or sodium imbalance. 3. Significant kidney disease 4. Hepatic encephalopathy (HE) or altered mental status requiring hospitalization; variceal bleeding or upper gastrointestinal bleeding; or type 1 hepatorenal syndrome with acute kidney injury (HRS-AKI) during the previous 3 months prior to Screening. 5. Acute-on-chronic liver failure. 6. Recipient of a patent transjugular intrahepatic portosystemic shunt (TIPS). 7. Known positive HIV serology confirmed by HIV viral load. 8. Subjects with acute infections, including acute viral hepatitis (subjects with chronic hepatitis B are eligible if treatment regimen is stable ≥ 3 months prior to study inclusion).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| maximum tolerated dose or optimal beneficial dose of PHIN-214 in multiple ascending dose; safety and tolerability. | may be up to six weeks | Incidence of adverse effects (type and severity), incidence of dose limiting toxicities, changes in key laboratory measures |
| Pharmacokinetics of PHIN-214 | up to six weeks | plasma concentration of PHIN-214 |
| Pharmacokinetics of PHIN-214 metabolite | up to six weeks | plasma concentration of PHIN-214 metabolite |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity of PHIN-214 | up to six weeks | anti-drug antibody testing |
Other
| Measure | Time frame | Description |
|---|---|---|
| Oxygenation level | up to six weeks | Oxygenation level by pulse oximeter |
| Blood pressure | up to six weeks | Blood pressure (vital signs) |
| Heart rate | up to six weeks | Heart rate (vital signs) |
| 12-lead ECG | up to six weeks | 12-lead ECG |
Countries
United States
Contacts
Primary ContactCynthia C Jones
Outcome results
None listed