A Study of the Use of Oral Posaconazole (POS) in the Treatment of Asymptomatic Chronic Chagas Disease (P05267)

Study Overview
=================
Brief Summary
-----------------
This is a study to compare the efficacy of oral posaconazole to placebo for the treatment of asymptomatic Chagas disease. The primary hypothesis of the study is that posaconazole 400 mg twice daily improves therapeutic response compared to placebo in participants with a diagnosis of asymptomatic chronic Chagas disease.

Official Title
-----------------
Phase 2 Proof-of-Activity Study of Oral Posaconazole in the Treatment of Asymptomatic Chronic Chagas Disease (Phase 2, Protocol No. P05267)

Conditions
-----------------
Chagas Disease

Intervention / Treatment
-----------------
* Drug: Posaconazole
* Drug: Placebo for posaconazole
* Drug: Benznidazole


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - Must have a positive serology result for Trypanosoma cruzi on any 2 of 3 of the following tests: indirect immunofluorescence, indirect hemagglutination, or enzyme-linked immunoabsorbent assay (ELISA) Must have a positive qualitative polymerase chain reaction (PCR) for Trypanosoma cruzi Must have a normal 12-lead electrocardiogram (ECG) Must have a normal 2-D echocardiogram Must have no evidence of ventricular tachycardia on 24-hour Holter monitoring Female participants of childbearing age must be using a medically accepted method of birth control before beginning study drug treatment and must agree to continue its use during the study, or must have been surgically sterilized Female participants of childbearing potential must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test at Screening and a negative urine pregnancy test at Baseline or within 72 hours before the start of study drug Exclusion Criteria: Are breastfeeding, pregnant, or planning to become pregnant Body weight <60 kg Have an immunodeficiency or are immunosuppressed History of megacolon with obstipation or megaesophagus with severe swallowing impairment. Have previously received treatment with benznidazole or nifurtimox Known allergy/sensitivity to azoles Has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than 2.5 times the upper limit of normal at Screening Has serum creatinine >2.5 mg/dL or 200 micromoles at Screening Has a history of severe alcohol abuse within two years from Screening Is taking any of the prohibited medication

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Posaconazole<br>Posaconazole (POS) 400 mg (10 mL) oral suspension twice daily for 60 days | Drug: Posaconazole<br>* POS 40 mg/mL oral suspension<br>* Other names: SCH 056592, MK-5592;|
| Placebo Comparator: Placebo<br>Posaconazole placebo (10 mL) oral suspension twice daily for 60 days | Drug: Placebo for posaconazole<br>* Placebo oral suspension<br>|
| Experimental: Posaconazole + Benznidazole<br>Posaconazole 400 mg (10 mL) oral suspension twice daily for 60 days and benznidazole (BNZ) 100 mg oral tablet twice daily (200-mg daily dose) for 60 days | Drug: Posaconazole<br>* POS 40 mg/mL oral suspension<br>* Other names: SCH 056592, MK-5592;Drug: Benznidazole<br>* BNZ 100 mg oral tablet<br>|
| Active Comparator: Benznidazole + Placebo<br>Posaconazole placebo (10 mL) oral suspension twice daily for 60 days and benznidazole 100 mg oral tablet twice daily (200-mg daily dose) for 60 days | Drug: Placebo for posaconazole<br>* Placebo oral suspension<br>Drug: Benznidazole<br>* BNZ 100 mg oral tablet<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Successful Response as Measured by Qualitative Polymerase Chain Reaction | Blood samples were collected for qualitative polymerase chain reaction (PCR) assay for Trypanosoma cruzi deoxyribonucleic acid (DNA). Successful response was defined as a negative qualitative PCR value at the Day 180 follow up visit. | Day 180 |