ClinicalTrials.gg
CompletedNCT07809919Updated Sep 9, 2026

A First-in-human, Safety, Tolerability, and Pharmacokinetics Study of LXE408 in Healthy Subjects

A Phase 1 interventional study of LXE408 and Placebo in Visceral Leishmaniasis and Chagas Disease, sponsored by Novartis Pharmaceuticals. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-09.

Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 1, Interventional, and Other

From the registry’s dates

  • Primary completion was Sep 2021, 5 years 1 month ago, and no results have been posted to the registry.
  • Registered 7 years 8 months after the study started (first participant enrolled Dec 2018, registered Aug 2026).
Phase
Phase 1
Study type
Interventional
Enrollment
88
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The purpose of this first-in-human study is to generate the necessary safety, tolerability, and pharmacokinetics (PK) information that will support further clinical development of LXE408 for the treatment of patients with visceral leishmaniasis and potentially Chagas disease.

02

Conditions studied

  • Visceral Leishmaniasis
  • Chagas Disease

Keywords

  • LXE408
  • first-in-human study
  • Phase l
  • First-in-human
  • healthy subject
  • single ascending dose
  • multiple ascending dose
  • visceral leishmaniasis
03

In context

Leishmaniasis, Visceral

68 studies on the registry are indexed under Leishmaniasis, Visceral; 7 are open to participants now.

This study's enrollment of 88 is below the median of 132 across 48 interventional studies indexed under Leishmaniasis, Visceral.

Browse Leishmaniasis, Visceral studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.

Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Written must be obtained before any assessment is performed.
  • Healthy male and female subjects 18 to 65 years of age included, and in good health as determined by past medical history, physical examination, vital signs, , and laboratory tests at screening and baseline.
  • At screening and baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position and again in the standing position. Sitting vital signs should be within the following ranges:

    • oral body temperature between 35.0-37.5 °C
    • systolic blood pressure between 90-139 mmHg
    • diastolic blood pressure between 50-89 mmHg
    • pulse rate between 40-90 bpm
  • Subjects must weigh at least 50 kg to participate in the study and must have a (BMI) within the range of 18 - 30 kg/m2. [BMI = Body weight (kg) / [Height (m)]2]
  • Able to communicate well with the investigator, to understand and comply with the requirements of the study.

Exclusion criteria

Exclusion Criteria:

  • Use of other drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations.
  • Known history or current cardiac arrhythmias.
  • Significant illness which has not resolved within two (2) weeks prior to baseline.
  • Recent (within the last three years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc.).
  • Recent (within the last three years) and/or recurrent history of acute or chronic bronchospastic disease (including asthma and , treated or not treated).
  • Chronic infection with (HBV) or (HCV). A positive HBV surface antigen (HBsAg) test, or if standard local practice, a positive HBV core antigen test, excludes a subject. Subjects with a positive HCV antibody test should have HCV RNA levels measured. Subjects with positive (detectable) HCV RNA should be excluded.
  • Known family history or known presence of long syndrome.
  • History of immunodeficiency diseases, or a positive (screening and confirmatory) test result.
  • History of of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or .
  • Donation or loss of 450 mL or more of blood within eight weeks prior to baseline, or longer if required by local regulation.
  • Plasma donation (450 mL) within 8 weeks prior to baseline.
  • levels or counts below the lower limit of normal for the laboratory.
  • History of drug abuse or unhealthy alcohol use within the 12 months prior to baseline, or evidence of such abuse as indicated by the laboratory assays conducted during screening #Unhealthy alcohol use is defined as a history of, or current alcohol misuse/abuse, defined as "Five or more drinks on the same occasion on each of 5 or more days in the past 30 days."
  • History of recreational cannabis use within four weeks prior to baseline. This exclusion criterion applies even if cannabis use is legalized where the site is located.
  • A history of clinically significant abnormalities, or any of the following ECG abnormalities at screening or baseline:

    • PR > 200 msec
    • QRS complex > 120 msec
    • QTcF > 450 msec (males)
    • QTcF > 460 msec (females)
  • Pregnant or nursing (lactating) women.
  • Smokers based on urine cotinine levels. Urine cotinine levels will be measured during screening and at each baseline for all subjects. Smokers will be defined as any subject who reports tobacco use and/or who has a urine cotinine ≥ 500 ng/mL.

Other protocol-defined inclusion/exclusion may apply

Terms in these criteria, in plain language(14)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

ECG (electrocardiogram)

A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

COPD

Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

QT and QTc

On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.

The study may name a correction formula and a limit in milliseconds, often around 450–480.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

05

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
88 participants (actual)

Study arms

  • Experimental
    Part A - Single Ascending Dose (SAD): Cohort 1: LXE408/Placebo

    Participants received a single ascending dose of LXE408 or Placebo (fasted).

    Drug: LXE408 · Drug: Placebo

  • Experimental
    Part A - SAD: Cohort 2: LXE408 /Placebo

    Participants received a single ascending dose of LXE408 or Placebo (fasted).

    Drug: LXE408 · Drug: Placebo

  • Experimental
    Part A - SAD: Cohort 3a/b: LXE408/Placebo

    Participants received a single ascending dose of LXE408 or Placebo (fasted and fed). This Cohort is divided into 2 parts: fasted and fed. Participants treated in cohort 3a (fasted) are mandated to return for cohort 3b (Food Effect) after at least a 7-day washout period between dosings.

    Drug: LXE408 · Drug: Placebo

  • Experimental
    Part A - SAD: Cohort 4: LXE408/Placebo

    Participants received a single ascending dose of LXE408 or Placebo (fasted).

    Drug: LXE408 · Drug: Placebo

  • Experimental
    Part A - SAD: Cohort 5: LXE408/Placebo

    Participants received a single ascending dose of LXE408 or Placebo (fasted).

    Drug: LXE408 · Drug: Placebo

  • Experimental
    Part B - Multiple ascending Dose (MAD): Cohort 1: LXE408/Placebo

    Participants received multiple ascending doses of LXE408 once daily or Placebo.

    Drug: LXE408 · Drug: Placebo

  • Experimental
    Part B - MAD: Cohort 2: LXE408/Placebo

    Participants received multiple ascending doses of LXE408 once daily or Placebo.

    Drug: LXE408 · Drug: Placebo

  • Experimental
    Part B - MAD: Cohort 3: LXE408/Placebo

    Participants received multiple ascending doses of LXE408 mg once daily or Placebo.

    Drug: LXE408 · Drug: Placebo

  • Experimental
    Part B - MAD: Cohort 4: LXE408/Placebo

    Participants received multiple ascending doses of LXE408 once daily or Placebo.

    Drug: LXE408 · Drug: Placebo

  • Experimental
    Part B - MAD: Cohort 5 (mGFR cohort): LXE408/Placebo

    Participants in this Measured glomerular filtration rate (mGFR) cohort received multiple ascending doses of LXE408 and iohexol or Placebo and iohexol.

    Drug: LXE408 · Drug: Placebo · Drug: Iohexol

  • Experimental
    Part B - MAD: Cohort 6: LXE408/Placebo

    Participants received multiple ascending doses of LXE408 once daily or Placebo.

    Drug: LXE408 · Drug: Placebo

Interventions

  • DrugLXE408

    LXE408 comes in film coated tablets and is taken orally.

  • DrugPlacebo

    LXE408 matching placebo comes in film coated tablets and is taken orally.

  • DrugIohexol

    Iohexol is a nonionic, water-soluble radiographic contrast medium with a molecular weight of 821.14 and is administered to the participant via intravenous (IV) injection.

06

What researchers measure

Primary outcomes

  1. Parts A & B: Number of participants with Adverse Events, physical exam findings, vital signs, ECG findings, safety laboratory assessments including chemistry, hematology, and urinalysis results

    To assess the safety and tolerability of of single and multiple ascending oral doses of LXE408.

    Time frame: Part A: Single Ascending Dose (SAD): 35 days; Part A: SAD (Food Effect): 63 days; Part B: Multiple Ascending Dose (MAD): 45 days

Secondary outcomes

  1. Pharmacokinetics (PK) of LXE408 and its metabolite MAN519: AUC (AUC0-24; AUCtau, AUClast, AUCinf as relevant) Parts A (SAD) & B (MAD)

    AUC, Area under Curve, represents the total amount of a drug that is actively present in the body over a specific period.

    Time frame: up to 72 hours post-dose for plasma PK in Part A, 48 hours post-dose for urine PK in Part A and Intensive PK samples for 24 hours post dose on Day 1 and 10 and trough samples from Day 2 to Day 9, in Part B

  2. Pharmacokinetics of MAN519: Metabolite to parent ratio (MPTR) for AUC: MTPR_AUC

    Metabolite-to-parent AUC ratio is the ratio of the overall exposure to a metabolite compared with the overall exposure to the parent drug.

    Time frame: up to 72 hours post-dose for plasma PK in Part A, 48 hours post-dose for urine PK in Part A and Intensive PK samples for 24 hours post dose on Day 1 and 10 and trough samples from Day 2 to Day 9, in Part B

  3. PK of LXE408 and its metabolite (MAN519) Parts A & B: Tmax

    Tmax, Time to Maximum, refers to the time required for a drug to reach its maximum concentration in the body.

    Time frame: up to 72 hours post-dose for plasma PK in Part A, 48 hours post-dose for urine PK in Part A and Intensive PK samples for 24 hours post dose on Day 1 and 10 and trough samples from Day 2 to Day 9, in Part B

  4. PK of LXE408 and its metabolite (MAN519) Parts A & B: Cmax

    Cmax, the maximum plasma concentration, is the highest peak concentration of a drug observed in the body's systemic circulation.

    Time frame: up to 72 hours post-dose for plasma PK in Part A, 48 hours post-dose for urine PK in Part A and Intensive PK samples for 24 hours post dose on Day 1 and 10 and trough samples from Day 2 to Day 9, in Part B

  5. PK of LXE408 Parts A & B: CL/F

    CL/F (Apparent Clearance) represents the efficiency of drug removal from the body following extravascular administration.

    Time frame: up to 72 hours post-dose for plasma PK in Part A, 48 hours post-dose for urine PK in Part A and Intensive PK samples for 24 hours post dose on Day 1 and 10 and trough samples from Day 2 to Day 9, in Part B

  6. PK of LXE408 Parts A & B: V/F

    V/F represents the apparent volume of distribution for a drug administered through a non-intravenous route.

    Time frame: up to 72 hours post-dose for plasma PK in Part A, 48 hours post-dose for urine PK in Part A and Intensive PK samples for 24 hours post dose on Day 1 and 10 and trough samples from Day 2 to Day 9, in Part B

  7. PK of LXE408 Part A (excluding Cohort 3b, Food effect cohort): Ae

    Ae stands for the cumulative amount of an unchanged drug excreted in the urine. It is a critical parameter used to measure how much of the active, unmetabolized medication is expelled from the body via the kidneys over a specific period of time.

    Time frame: up to 72 hours post-dose for plasma PK in Part A, 48 hours post-dose for urine PK in Part A

  8. PK of LXE408 Part A (excluding Cohort 3b, Food effect cohort): CLR

    CLR stands for renal clearance. It is the volume of plasma completely cleared of a drug by the kidneys per unit of time. It represents the rate at which the kidneys filter, secrete, and excrete a specific medication into the urine.

    Time frame: up to 72 hours post-dose for plasma PK in Part A, 48 hours post-dose for urine PK in Part A

  9. PK of LXE408 and its metabolite (MAN519) Parts A & B: T1/2

    T1/2 (half-life) is the time required for the concentration of a drug in the body or bloodstream to reduce by exactly 50%.

    Time frame: up to 72 hours post-dose for plasma PK in Part A, 48 hours post-dose for urine PK in Part A and and Intensive PK samples for 24 hours post dose on Day 1 and 10 and trough samples from Day 2 to Day 9, in Part B

  10. Plasma clearance of iohexol (measured glomerular filtration rate (mGFR) cohort) (Part B only)

    To measure renal function (glomerular filtration rate (GFR)) after administration of LXE408.

    Time frame: Day -1 (before LXE408 administration), Day 5 & Day 10 (Post LXE408 administration) at 0,0.5,1,2,3,4,6,8,10,12 hours (post- iohexol dose)

07

Study locations

1 site
  • Vince and Associates PA and Vince and Associates Inc
    Overland Park, Kansas 66212, United States
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 9, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07809919
Responsible party
Sponsor
First posted
Sep 9, 2026
Start date
Dec 21, 2018
Primary completion
Sep 27, 2021
Completion
Sep 27, 2021
Last update
Sep 9, 2026

Study contacts

Novartis Pharmaceuticals
study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: LXE408

Start the discussion