A First-in-human, Safety, Tolerability, and Pharmacokinetics Study of LXE408 in Healthy Subjects
A First-in-human, Randomized, Subject Blinded, Placebo Controlled, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of LXE408 in Healthy Subjects
1 other identifier
interventional
88
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2018
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 21, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 27, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
September 27, 2021
CompletedFirst Submitted
Initial submission to the registry
August 26, 2026
CompletedFirst Posted
Study publicly available on registry
September 9, 2026
CompletedSeptember 9, 2026
September 1, 2026
2.8 years
August 26, 2026
September 8, 2026
Conditions
Keywords
Outcome Measures
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.
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 (10)
Pharmacokinetics (PK) of LXE408 and its metabolite MAN519: AUC (AUC0-24; AUCtau, AUClast, AUCinf as relevant) Parts A (SAD) & B (MAD)
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
Pharmacokinetics of MAN519: Metabolite to parent ratio (MPTR) for AUC: MTPR_AUC
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
PK of LXE408 and its metabolite (MAN519) Parts A & B: Tmax
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
PK of LXE408 and its metabolite (MAN519) Parts A & B: Cmax
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
PK of LXE408 Parts A & B: CL/F
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 more secondary outcomes
Study Arms (11)
Part A - Single Ascending Dose (SAD): Cohort 1: LXE408/Placebo
EXPERIMENTALParticipants received a single ascending dose of LXE408 or Placebo (fasted).
Part A - SAD: Cohort 2: LXE408 /Placebo
EXPERIMENTALParticipants received a single ascending dose of LXE408 or Placebo (fasted).
Part A - SAD: Cohort 3a/b: LXE408/Placebo
EXPERIMENTALParticipants 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.
Part A - SAD: Cohort 4: LXE408/Placebo
EXPERIMENTALParticipants received a single ascending dose of LXE408 or Placebo (fasted).
Part A - SAD: Cohort 5: LXE408/Placebo
EXPERIMENTALParticipants received a single ascending dose of LXE408 or Placebo (fasted).
Part B - Multiple ascending Dose (MAD): Cohort 1: LXE408/Placebo
EXPERIMENTALParticipants received multiple ascending doses of LXE408 once daily or Placebo.
Part B - MAD: Cohort 2: LXE408/Placebo
EXPERIMENTALParticipants received multiple ascending doses of LXE408 once daily or Placebo.
Part B - MAD: Cohort 3: LXE408/Placebo
EXPERIMENTALParticipants received multiple ascending doses of LXE408 mg once daily or Placebo.
Part B - MAD: Cohort 4: LXE408/Placebo
EXPERIMENTALParticipants received multiple ascending doses of LXE408 once daily or Placebo.
Part B - MAD: Cohort 5 (mGFR cohort): LXE408/Placebo
EXPERIMENTALParticipants in this Measured glomerular filtration rate (mGFR) cohort received multiple ascending doses of LXE408 and iohexol or Placebo and iohexol.
Part B - MAD: Cohort 6: LXE408/Placebo
EXPERIMENTALParticipants received multiple ascending doses of LXE408 once daily or Placebo.
Interventions
LXE408 comes in film coated tablets and is taken orally.
LXE408 matching placebo comes in film coated tablets and is taken orally.
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.
Eligibility Criteria
You may qualify if:
- Written informed consent 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, electrocardiogram, 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 body mass index (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.
You may not qualify if:
- Use of other investigational 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 clinically significant 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 chronic obstructive pulmonary disease, treated or not treated).
- Chronic infection with Hepatitis B (HBV) or Hepatitis C (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 QT syndrome.
- History of immunodeficiency diseases, or a positive HIV (screening and confirmatory) test result.
- History of malignancy 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 metastases.
- 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.
- Hemoglobin levels or platelet 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."
- A history of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening or baseline:
- PR \> 200 msec
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Vince and Associates PA and Vince and Associates Inc
Overland Park, Kansas, 66212, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- exploratory, first-in-human, randomized, subject blinded, placebo-controlled, single and multiple ascending oral dose study in healthy volunteers
- Purpose
- OTHER
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 26, 2026
First Posted
September 9, 2026
Study Start
December 21, 2018
Primary Completion
September 27, 2021
Study Completion
September 27, 2021
Last Updated
September 9, 2026
Record last verified: 2026-09
Data Sharing
- IPD Sharing
- Will not share