Dedicated QT Study in Bolivian Patients Taking Impavido® (Miltefosine) for Mucocutaneous Leishmaniasis
Dedicated QT Study in Bolivian Patients Taking Impavido® (Miltefosine) for Mucocutaneous Leishmaniasis
This study is a Phase 4, open-label, single group study in which at least 40 adult patients
 undergoing miltefosine treatment for mucocutaneous leishmaniasis (CL and ML) will be assessed
 by 12-lead ECG for prolongation of the corrected QT interval
This study is a Phase 4, open-label, single group study in which at least 40 adult patients
 undergoing miltefosine treatment for mucocutaneous leishmaniasis will be assessed by digital
 12-lead electrocardiogram (ECG) for prolongation of the corrected QT (QTc) interval.
 Potential subjects diagnosed with mucocutaneous leishmaniasis who are planning to undergo
 miltefosine treatment will be informed about the study and undergo the informed consent
 process. After obtaining informed consent, subjects will be screened over a 14-day period for
 eligibility by medical history including leishmaniasis diagnostics, physical examination,
 clinical laboratory measurements [chemistries: alanine aminotransferase (ALT), total
 bilirubin, creatinine, magnesium, calcium, potassium, sodium; hematology: white blood cell
 (WBC) count, hemoglobin, platelet count; and a pregnancy test if female], ECG, and medication
 use in the 28-day period before starting treatment. If eligible for the study, the subject
 will receive miltefosine for 28 days at a target dose of approximately 2.5 mg/kg/day.
 Screening and enrollment into the study will continue until at least 10 females and up to 30
 males complete the study and are considered evaluable (provide Day 28 ECGs and
 pharmacokinetic (PK) samples and complete at least 25 of 28 days of miltefosine treatment).
 Vital signs will be collected weekly during treatment. Chemistries and hematology will be
 repeated at study Days 14 (mid-treatment) and 28 (end of treatment). A pregnancy test (if
 applicable) will be repeated at Day 28. ECGs (12-lead) will be repeated at Days 14 and 28.
 Blood will be drawn for PK assessments on Days 14 and 28 within 15 minutes of the final ECG.
 Adverse events (AEs) and concomitant medication use will be collected during treatment. If on
 Day 28, clinically significant abnormalities are observed by ECG, then a repeat ECG and PK
 blood draw will be performed at Day 42 (2 weeks after completing treatment). AEs and
 concomitant medication use will also be collected in any subject coming back for the Day 42
 visit. Digital ECGs (12-lead) will be collected in triplicate at each time point over a
 period not to exceed 1 hour. During treatment, ECGs will be collected 4 hours after a dose
 (approximate Tmax).
Inclusion Criteria:

 1. Provide written informed consent

 2. Be available to complete study procedures

 3. Have a diagnosis of mucocutaneous leishmaniasis confirmed by microscopy of a stained
 smear of a lesion sample, by culture of a lesion sample, or by polymerase chain
 reaction (PCR) of a lesion sample or by Montenegro skin test and be willing to undergo
 treatment with miltefosine

 4. Be male or female and 18-55 years of age

 5. Have alanine aminotransferase (ALT), total bilirubin, and creatinine < 1.5 x upper
 upper limit of normal (ULN)

 6. Have white blood cell (WBC) count, hemoglobin, and platelet count within 15% of within
 normal limits (WNL)

 7. Be without clinically significant non-cardiac medical disorder

 8. Have 12-lead corrected QT interval using the Fridericia method (QTcF) interval < 450
 msec, abnormal heart rate (< 40 or > 120 beats/min), PR interval (from 131 msec to 197
 msec for males and 120 msec to 196 msec for females, or QRS interval (from 78 msec to
 126 msec for males and 74 msec to 114 msec for females)

 9. Have blood levels of ions that might affect ECG: (magnesium 1.82 mg/dL to 2.41 mg/dL,
 calcium 8.5 mg/dL to 10.5 mg/dL, potassium 3.5 milliequivalents/liter (mEq/L) to 10.5
 mEq/L, and sodium 135 mEq/L to 148 mEq/L)

 10. Have no family history of sudden cardiac death before age 40

 11. Have no personal history ischemic heart disease, congestive heart failure,
 palpitations, dizziness, syncope, cardiac arrhythmias

 12. If female, agree to use an effective method of birth control from the start of
 treatment until 5 months after completing treatment and have a negative pregnancy test

 Exclusion Criteria:

 1. Be a female who is breast feeding

 2. Be a female who is pregnant

 3. In the past 28 days prior to the start of miltefosine treatment have received any drug
 or other treatment that is known to significantly affect the QTc interval

 4. Have positive serology for Chagas disease