Single Dose Escalation of PHIN-214 in Child-Pugh A Liver Cirrhotics
Study Details
Study Description
Brief Summary
This single ascending dose (SAD) study evaluates PHIN-214, being studied to determine the safety, tolerability, and pharmacokinetics, and establish the maximum tolerated dose of this compound in patients with compensated cirrhosis.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
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 Europe for the treatment of bleeding esophageal varices and HRS type 1 and is usually administered as an IV bolus.
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. As a partial V1a agonist that traffics into the bloodstream from a subcutaneous depot, this derivative is designed to be gentler than terlipressin and has been well tolerated at the injection site, to date.
This study will evaluate the use of PHIN-214 administered once at various dosing levels to establish the maximum tolerated dose in patients with compensated cirrhosis.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: single dose of PHIN-214 single ascending dose of PHIN-214 |
Drug: PHIN-214 Subcutaneous injection
Single subcutaneous injection with PHIN-214 terlipressin derivative, single ascending dose
Other Names:
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Outcome Measures
Primary Outcome Measures
- Incidence of dose limiting toxicities [up to two weeks]
Incidence of dose limiting toxicities
- incidence of stopping criteria [up to two weeks]
incidence of stopping criteria
- incidence of AEs [up to two weeks]
incidence of AEs
Secondary Outcome Measures
- PK of PHIN-214 [up to two weeks]
plasma concentration of PHIN-214
- AUC of PHIN-214 [up to two weeks]
AUC of PHIN-214
- PK of PHIN-214 metabolite [up to two weeks]
plasma concentration of PHIN-214 metabolite
- AUC of PHIN-214 metabolite [up to two weeks]
AUC of PHIN-214 metabolite
Other Outcome Measures
- various exploratory markers of efficacy [up to two weeks]
systolic and diastolic blood pressure
Eligibility Criteria
Criteria
Inclusion Criteria:
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Body mass index within the range 18 to 40 kg/m2 (inclusive) at screening.
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Females must be non-pregnant, non-lactating or of non-childbearing potential or using highly efficient contraception for the full duration of the study.
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Patients with liver cirrhosis confirmed by reliable biopsy (within 12 months) or reliable Fibroscan >15 kPa at screening.
Exclusion Criteria:
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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.
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History of diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, or any other disorder associated with fluid or sodium imbalance.
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Significant kidney disease
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Estimated glomerular filtration rate (eGFR by CKD-Epi) <90 ml/min/1.73 m2 or Cr >1.2 mg/dL.
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Hepatic encephalopathy ≥ grade 1.
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Patients with Grade ≥ 3 or larger esophageal varices (per Conn's classification of esophageal varices) or red spots on most recent eligibility EGD.
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Recipient of a transjugular intrahepatic portosystemic shunt (TIPS).
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Use of treatments for Hepatitis C virus within 6 months of Screening or anticipated use during the trial. Positive HCV antibody serology with detectable HCV ribonucleic acid (RNA).
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Known positive HIV serology confirmed by HIV viral load.
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Patients with acute hepatitis B; pPatients with known chronic hepatitis B are eligible if treatment regimen is not changed in the 4 weeks prior to study inclusion
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Arizona Liver Health | Chandler | Arizona | United States | 85224 |
2 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
Sponsors and Collaborators
- PharmaIN
Investigators
- Study Chair: Cynthia C Jones, BS, PharmaIN
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PHIN-001