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
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
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.
Inclusion Criteria:
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:
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.
Exclusion Criteria:
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."
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 ECG abnormalities, or any of the following ECG abnormalities at screening or baseline:
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