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Drug interaction study of leniolisib with a drug combination in healthy volunteers for Activated PI3K Delta Syndrome

Verified siteRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

The study involves the rare immune disorder Activated Phosphoinositide 3-Kinase Delta Syndrome. The investigational medicine being examined is CDZ173/Leniolisib, an oral drug that targets a specific pathway involved in the disease. In the same participants, a group of commonly used medicines – a coffee stimulant caffeine, a sleep‑inducing medication midazolam, a cholesterol‑lowering pill rosuvastatin, a water‑pill that helps remove excess fluid furosemide, and a diabetes medication metformin – will be given together to see how they interact.

The purpose of the study is to assess whether the investigational drug changes the way the body handles these other medicines. This type of assessment looks at the pharmacokinetics, which means how quickly a drug is absorbed, how it spreads through the body, and how it is eliminated. Each of the test medicines is processed by specific enzymes or transport proteins, such as the enzyme family CYP3A4, which helps break down many drugs.

Healthy volunteers will take the study drug once daily for several days until steady levels are reached. After that, a single dose of the five test medicines will be taken together, and blood and urine samples will be collected over the next many hours to measure the amount of each drug in the body. Throughout the study, participants will have their vital signs checked, simple blood and urine tests performed, and a routine heart‑electrical test (ECG) to monitor safety.

The research process

The trial runs in 4 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Start Lenioslisib Treatment

    You will take leniolisib 140 mg as a film‑coated tablet by mouth once each day.

    The medication will be taken for the entire duration of the study.

  2. Step 2

    Take Study Cocktail

    After several days of leniolisib, you will receive a single oral dose of each of the following drugs on the same day:

    Caffeine 100 mg (a stimulant found in coffee).

    Midazolam 2 mg (a medication that can affect the activity of certain liver enzymes).

    Rosuvastatin 5 mg (a cholesterol‑lowering medicine).

    Furosemide 5 mg (a diuretic that helps the body remove excess fluid).

    Metformin 500 mg (a medication commonly used for blood‑sugar control).

    All five drugs are taken by mouth at the same time while you continue to take leniolisib.

  3. Step 3

    Blood Sample Collection

    Blood will be drawn at several time points after the cocktail to measure how each drug is absorbed and cleared.

    These samples help determine the area under the concentration‑time curve (AUC) and the maximum concentration (Cmax) for each medication.

  4. Step 4

    Continue Lenioslisib and Safety Monitoring

    You will keep taking leniolisib 140 mg each day until the end of the study.

    Your vital signs, routine electrocardiogram (ECG), and laboratory tests (blood counts, chemistry, and urine analysis) will be checked regularly.

    Any side effects you experience will be recorded and evaluated.

Who can join the trial?

18 criteria

  • Age: You must be between 18 and 60 years old, inclusive.
  • Female participants must not be able to become pregnant. This means you are either surgically sterilized, have not had a period for at least 12 months (post‑menopausal) with a hormone level (FSH) over 40 mU/mL, or otherwise physiologically unable to conceive. You also need a negative blood pregnancy test at screening and a negative urine pregnancy test when you arrive at the clinic.
  • Prescription medicines must have been stopped at least 30 days before you come to the clinic.
  • Over‑the‑counter medicines, vitamins, supplements and herbal products (such as St. John’s wort) must have been stopped at least 14 days before you come to the clinic. The only exception is acetaminophen (paracetamol), which you may continue up to the day you arrive.
  • You must agree not to drink any alcohol for at least 48 hours (2 days) before the screening visit and before you are admitted to the clinic.
  • You must agree not to consume any foods or drinks that contain caffeine (e.g., coffee, tea, cola, chocolate, energy drinks) for at least 48 hours before the screening visit and before admission.
  • You must avoid grapefruit or any product that contains grapefruit for at least 7 days before admission.
  • You must understand what the study involves and give written permission (informed consent) to take part.
  • Body‑mass index (BMI) must be between 18.5 and 30.0 kg/m². BMI is a measure that compares your weight to your height.
  • You must be judged to be in good health based on your medical history, a physical exam, vital signs (like blood pressure and heart rate), and safety lab tests performed at screening.
  • Your liver function tests must be normal:
    • Alanine transaminase (ALT) and aspartate transaminase (AST) must be at or below the laboratory’s upper limit of normal.
    • Total bilirubin must be no more than 1.5 times the upper limit of normal (if you have Gilbert’s syndrome, the direct bilirubin must be 0.5 mg/dL or less).
    • Alkaline phosphatase must be at or below the upper limit of normal.
    • Your kidney function, measured by the estimated glomerular filtration rate (eGFR), must be 90 mL/min or higher. eGFR estimates how well your kidneys filter waste.
    • If you are a fertile male, you must either remain abstinent or use a condom together with a highly effective form of birth control used by your female partner (such as hormonal pills, implants, intrauterine device, or tubal ligation) from the first day you enter the clinic until 3 months after the last study dose. Men who donate sperm are not allowed during this time. Women who are pre‑menarchal, post‑menopausal, or have had surgical removal of both ovaries are exempt.
    • You must have a normal electrocardiogram (ECG) at screening. An ECG records the electrical activity of the heart.
    • You must be willing to follow all study‑related procedures and restrictions.
    • You must be a non‑smoker or have stopped smoking at least 3 months before the study.

Who cannot join the trial?

18 criteria

  • Employee of the contract research organization (CRO) or the Sponsor – anyone who works for the company running the study or the company funding it cannot join.
  • Known allergy or intolerance to any of the study medicines (leniolisib, caffeine, midazolam, rosuvastatin, furosemide, metformin) or similar drugs (like benzodiazepines or sulfonamides), or to ingredients in the pills, or a history of severe allergies (including latex) or a serious allergic reaction called anaphylaxis, or strong reactions to prescription or over‑the‑counter medicines or foods.
  • History of serious medical problems affecting hormones (endocrine), stomach or intestines (gastrointestinal), heart or blood vessels (cardiovascular), blood cells (hematological), liver (hepatic), immune system (immunological), kidneys (renal), breathing (respiratory), cancer (neoplastic) or urinary/genital organs (genitourinary).
  • Any illness that the doctor believes could confuse the study results or make participation riskier for you.
  • Any surgery or medical condition that could significantly change how your body absorbs, distributes, breaks down, or removes a drug (examples: removal of part of the stomach, weight‑loss surgery, removal of part of the small or large intestine).
  • Being mentally or legally unable to give consent, having major emotional problems now or expected during the study, or having a serious mental health disorder in the past year.
  • Being unable or unwilling to stop taking any other medicines for the entire study period.
  • Drinking more than 14 alcoholic drinks per week (one drink is about 284 mL of beer, 125 mL of wine, or 25 mL of distilled spirits).
  • Current regular use of illegal drugs (including recreational use) or a history of drug or alcohol abuse within the past year.
  • Having anemia at screening, defined as a hemoglobin level less than 13.5 g/dL for men or less than 12.0 g/dL for women. (Hemoglobin is the protein in red blood cells that carries oxygen.)
  • Having major surgery, or having donated or lost about 500 mL of blood (one unit) within the 3 months before the screening visit.
  • Having taken any other experimental (investigational) drug within the past 90 days.
  • Having participated in more than four other clinical studies in the 12 months before receiving the first dose of this study.
  • Testing positive for hepatitis B surface antigen, hepatitis C antibodies, or HIV‑1/2 antibodies (these are tests for certain viral infections).
  • Having veins that are not suitable for taking blood samples.
  • Having a significant or sudden illness within 5 days before receiving the study drug that could affect safety assessments, according to the doctor.
  • If the doctor has any concern about your safety or any other reason that makes you unsuitable for the study.
  • Receiving any vaccination within 14 days before the first dose or having a vaccination scheduled before the follow‑up visit.
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Investigated drugs

  • Leniolisib

    is an experimental medicine being tested as the main drug in this study. Researchers are giving it to healthy volunteers to see how it might change the way the body processes other medicines. The goal is to find out whether leniolisib can cause drug‑drug interactions that could affect the safety or effectiveness of other commonly used drugs.

  • Caffeine

    is a well‑known stimulant found in coffee and tea. In this trial it is used as a “probe” drug to check the activity of a liver enzyme called CYP1A2. By measuring how caffeine is processed in the presence of leniolisib, scientists can see if leniolisib affects this enzyme’s function.

  • Midazolam

    is a medication that can make people feel relaxed or sleepy. It is used in the study as a probe for another liver enzyme, CYP3A4. The researchers look at how midazolam is broken down when leniolisib is taken, which helps them understand if leniolisib interferes with this enzyme.

  • Rosuvastatin

    is a cholesterol‑lowering pill. In the study it serves as a probe for transport proteins called BCRP, OATP1B1, and OATP1B3. By watching how rosuvastatin moves in the body with and without leniolisib, the team can learn whether leniolisib affects these transport pathways.

  • Furosemide

    (often known by the brand name Lasix) is a diuretic that helps the body get rid of excess fluid. It is used here to test the activity of a kidney transporter called OAT3. The trial examines whether leniolisib changes how furosemide is handled by the kidneys.

  • Metformin

    is a common medicine for type 2 diabetes. In this study it acts as a probe for kidney transporters named MATE and OCT2. Researchers measure metformin’s levels to see if leniolisib influences these transport systems.

What is already known about the treatment

  • Furosemide

    This medication is given as an oral solution that you drink. It is an approved loop diuretic used to treat fluid buildup in conditions like heart failure or kidney disease. It works by stopping the kidneys from re‑absorbing sodium, which makes the body get rid of extra water. It belongs to the class of loop diuretics.

  • Leniolisib

    Leniolisib comes as a film‑coated tablet taken by mouth. It is an orphan‑drug that has been approved for the rare immune disorder Activated Phosphoinositide 3‑Kinase Delta Syndrome. The drug blocks the PI3Kδ enzyme, helping to normalize immune cell activity. It is classified as a selective PI3Kδ inhibitor.

  • Rosuvastatin

    Rosuvastatin is taken as an oral tablet. It is a widely approved medication used to lower high cholesterol and reduce the risk of heart disease. It works by inhibiting the HMG‑CoA reductase enzyme, which lowers the amount of cholesterol made by the liver. It belongs to the statin class of drugs.

  • Midazolam

    Midazolam is administered as an oral tablet that you swallow. It is an approved sedative used for anxiety, sleep induction, or procedural sedation. The drug enhances the activity of GABA receptors in the brain, producing a calming effect. It is classified as a benzodiazepine.

  • Caffeine

    Caffeine is taken orally in tablet or pill form. It is an over‑the‑counter stimulant used to increase alertness and reduce fatigue. It works by blocking adenosine receptors, which prevents the feeling of tiredness. It is classified as a central nervous system stimulant.

  • Metformin

    Metformin is taken as an oral tablet. It is an approved first‑line treatment for type 2 diabetes to help control blood sugar. The drug reduces the amount of glucose the liver releases and makes the body use insulin more effectively. It belongs to the biguanide class of antidiabetic drugs.

Investigated diseases

Activated Phosphoinositide 3-Kinase Delta Syndrome - Activated Phosphoinositide 3‑Kinase Delta Syndrome (APDS) is a rare genetic immune disorder caused by gain‑of‑function mutations that increase activity of the PI3Kδ enzyme. The overactive enzyme leads to abnormal development and function of B and T lymphocytes. Affected individuals often experience recurrent infections, enlarged lymph nodes, and an enlarged spleen. Over time, the immune system may become increasingly dysregulated, leading to persistent inflammation and autoimmune features. Some patients develop abnormal growth of lymphoid tissue that can evolve into lymphoproliferative disease. The condition typically begins in childhood but can continue to change throughout life.
Trial detailsLast updated 14 Oct 2026
Age18+ yearsPhasePhase ITrial ID2023-507134-25-00Protocol codeLE 5101Estimated enrolment20 patientsSponsorPharming Technologies B.V.

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