An open-label, single-dose, parallel-group study to evaluate the plasma pharmacokinetics of leniolisib in subjects with impaired hepatic function and in subjects with normal hepatic functio

Phase 1

• Conditions: Activated Phosphoinositide 3-Kinase Delta Syndrome; MedDRA version: 20.0Level: PTClassification code: 10078281Term: Activated PI3 kinase delta syndrome Class: 100000004850; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: CTIS2023-508519-22-00
• Lead Sponsor: Pharming Technologies B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-11-02
• Study Completion: 2024-06-09
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

Control or hepatically (moderately and severely) impaired male or female subjects of non-childbearing potential who, at the time of Screening, are between the ages of 18 and 79 years, inclusive., No known or suspected HI., Control is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure (BP) and pulse rate (PR) measurement, 12 lead electrocardiograms (ECG), or clinical laboratory tests., Satisfy the criteria for Class B (Cohort 1) or Class C (Cohort 3), of the Child-Pugh Classification., A diagnosis of hepatic dysfunction due to hepatocellular disease (and not secondary to any acute ongoing hepatocellular process) or toxic liver damage (caused by amongst others by alcohol abuse) documented (6 months) by medical history, physical examination, liver biopsy, fibroscan, hepatic ultrasound, computerized tomography (CT) scan, or magnetic resonance imaging (MRI)., Known stable HI, defined as no evidence of clinically significant change in disease status within the last 30 days, as documented by the subject’s recent medical history (e.g., no worsening clinical signs of HI, or no worsening of total bilirubin or prothrombin time by more than 50%)., Stable drug regimen defined as not starting a new drug or changing dosage within seven days or five half-lives (whichever is longer) prior to the dosing of investigational product., History of alcohol abuse is permissible providing that the results of alcohol test are negative at Screening and on Day -1, and the subject is willing and able to abide by the lifestyle guidelines., Female subjects of non-childbearing potential must meet at least 1 of the following criteria: a.Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; with a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state (>40 mU/mL); b.Have undergone a documented hysterectomy and/or bilateral oophorectomy; or c.Have medically confirmed ovarian failure., For this study, a fertile male subject must be abstinent, or must agree to use a condom together with a highly effective method of contraception by the female partner of childbearing potential, when sexually active from first admission to the clinical research center until 3 months (90 days) after the last dose. Highly effective methods of contraception to be used by female partners are the following: a.Hormonal contraception that inhibits ovulation: combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, or transdermal) or progestogen-only hormonal contraception (oral, injectables or implants) b.Intrauterine device or intrauterine hormone-releasing system c.Bilateral tubal occlusion of the female partner performed at least 3 months prior to the Screening Visit Notes: Sperm donation is not allowed from first admission to the clinical research center until 3 months (90 days) after the last dose. Subjects who practice true abstinence, because of the subject’s lifestyle choice (i.e., the subject should not become abstinent just for the purpose of study participation), are exempt from contraceptive requirements. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. If a subject who is abstinent at the time of signing the informed

Exclusion Criteria

Any surgical (e.g., gastrectomy, bariatric surgery, small bowel or large bowel resection) or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug., History of known sensitivity or intolerability to leniolisib to any related compound or excipients in the formulation., Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the dose of leniolisib (whichever is longer)., Subjects with a history of or current positive results for human immunodeficiency virus (HIV)., Other acute or chronic medical or psychiatric condition(s) including recent (within the past year) or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study., Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies deemed relevant for participation in this study, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing)., History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink=5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening., Screening supine BP =140 (160 for subjects >60 years) mm Hg (systolic) or =90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is =140 (or >160) mm Hg (systolic) or =90 mm Hg (diastolic), the BP should be repeated once to determine the subject’s eligibility., 12-lead ECG demonstrating QTcF >450 msec (QTcF > 470 msec for females) or a QRS interval >120 msec at Screening. If QTcF exceeds 450 (or 470) msec, or QRS exceeds 120 msec, the ECG should be repeated once to determine the subject’s eligibility., Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to dosing of leniolisib. As an exception, acetaminophen/paracetamol may be used at doses of =1 g/day. Limited use of nonprescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor. Herbal supplements and hormone replacement therapy must have been discontinued at least 28 days prior to the dose of investigational product., Subjects who test positive for HBsAg, human immunodeficiency virus (HIV)-1 or HIV-2 antibody, or HCV antibody at screening will be excluded, unless in the latter case, participants with a positive HCV antibody test can be enrolled if they have negative HCV RNA at screening and documented negative HCV RNA at least 6 months prior to screening., A positive urine drug test. Subjects with HI (Cohorts 1 and 3) will be eligible to participate if their urine drug test is positive with a drug for a prescribed substance that is not expected to interfere with the PK of leniolisib., Any vaccination within 14 days prior to first dosing or scheduled before the follow-up visit., Mild HI (Child Pugh Class A), Other clinically significant disease that contraindicates study drug or that may affect the PK of leniolisib (stable, chronic, con

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified