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

Study Overview

• Status: Completed
• Conditions: Mucocutaneous Leishmaniasis
• Intervention / Treatment: Drug: Miltefosine

Detailed Description

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).

• Study Type: Observational
• Enrollment (Actual): 42

Contacts and Locations

Study Locations

• Bolivia
  • Santa Cruz, Bolivia
    • Funderma

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Persons with mucocutaneous leishmaniasis being treated with miltefosine

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Miltefosine; Miltefosine: target of 2.5 mg/kg/day for 28 days	Drug: Miltefosine; Other Names: Impavido

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mean value of corrected QT interval	QTcF	up to 2 weeks after end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients with adverse events	AEs and SAEs	up to 2 months after end of treatment

Collaborators and Investigators

• Sponsor: Knight Therapeutics (USA) Inc

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): June 6, 2017
• Study Completion (Actual): March 6, 2018

Study Registration Dates

• First Submitted: April 22, 2015
• First Submitted That Met QC Criteria: April 24, 2015
• First Posted (Estimate): April 29, 2015

Study Record Updates

• Last Update Posted (Actual): September 4, 2020
• Last Update Submitted That Met QC Criteria: September 2, 2020
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: miltefosine; leishmaniasis; EKG
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Euglenozoa Infections; Leishmaniasis, Cutaneous; Leishmaniasis; Leishmaniasis, Mucocutaneous; Anti-Infective Agents; Antineoplastic Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Miltefosine
• Other Study ID Numbers: MILT 2127-3