Duvelisib in Hepatically Impaired Subjects Compared to Healthy Subjects

Study Overview
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Brief Summary
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To evaluate the pharmacokinetics, safety, and tolerability of IPI-145 when administered to subjects with chronic hepatic impairment and in matched healthy subjects.

Detailed Description
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This is a nonrandomized, open-label, parallel-group, single oral dose study in subjects with chronic hepatic impairment and matched (age, sex, weight, BMI) healthy subjects. Subjects will be enrolled into 1 of 3 groups based on hepatic impairment grade: mild, moderate and normal hepatic function. An optional severe hepatic impairment group will enroll based on data from the mild and moderate hepatic impairment groups in comparison to matched healthy group. All subjects will receive a single oral dose of IPI-145 25 mg.

Official Title
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A Phase 1, Open-Label, Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Single Dose of Duvelisib in Subjects With Chronic Hepatic Impairment Compared to Healthy Subjects

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: IPI-145


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women of nonchildbearing potential between 18-70 years of age Body Mass Index (BMI): 18.0 - 38.0 kg/m2. Healthy subjects: in good health, determined by no clinically significant findings from clinical evaluations Hepatic impairment subjects: confirmed hepatic impairment >1 year with etiology of chronic alcoholism, chronic viral hepatitis (B or C), nonalcoholic steatohepatitis, autoimmune hepatitis, Wilson disease, alpha-1 antitrypsin deficiency, glycogen storage diseases, or galactosemia Provided written informed consent prior to any study specific procedures Exclusion Criteria: Women of childbearing potential Hepatic impairment subjects: fluctuating or rapidly deteriorating hepatic function, acute hepatitis, variceal bleeding within 8 weeks of screening, a history of pancreatitis within 8 weeks of screening, evidence of hepatic encephalopathy > Grade 1, current unstable hematologic condition, and/or creatinine clearance < 60 mL/min Healthy subjects: positive screening test for hepatitis B surface antigen, or hepatitis C antibody ECG at screening or Day -1 showing QTcF ≥ 450 msec for healthy subjects or > 500 msec for hepatically impaired subjects Evidence of clinically significant medical conditions History of gastrointestinal disease or surgery that may affect drug absorption Positive or indeterminate QuantiFERON-TB Gold test at screening Any active infection at the time of screening or admission

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mild Hepatic Impairment<br> | Drug: IPI-145<br>* 25 mg single oral capsule<br>|
| Experimental: Moderate Hepatic Impairment<br> | Drug: IPI-145<br>* 25 mg single oral capsule<br>|
| Experimental: Healthy Subjects<br> | Drug: IPI-145<br>* 25 mg single oral capsule<br>|
| Experimental: Severe Hepatic Impairment<br>Optional arm based on results from Arms 1, 2, and 3 | Drug: IPI-145<br>* 25 mg single oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of IPI-145 and its primary metabolite, IPI-656 | PK parameters (AUC, Cmax and t1/2) of IPI-145 and its metabolite, IPI-656 Plasma concentrations of IPI-145 and its metabolite, IPI-656 | Open 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events following administration of IPI-145 | Safety Findings | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, hepatic impairment