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

• Posaconazole (Drug), also known as SCH 056592, MK-5592: POS 40 mg/mL oral suspension
• Placebo for posaconazole (Drug): Placebo oral suspension
• Benznidazole (Drug): BNZ 100 mg oral tablet

Primary outcomes

• Percentage of Participants With a Successful Response as Measured by Qualitative Polymerase Chain Reaction [Day 180]: 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.

Sex: All, ages: 18 Years to 50 Years

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

Participant flow

Outcome results

• Percentage of Participants With a Successful Response as Measured by Qualitative Polymerase Chain Reaction (Primary), Number, Percentage of participants: Posaconazole 15.6 (6.9 to 31.8); Placebo 10.0 (3.5 to 25.6); Posaconazole + Benznidazole 82.1 (64.4 to 92.1); Benznidazole + Placebo 86.7 (70.3 to 94.7)

Adverse events

Time frame: All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)

Serious adverse events by term

Other adverse events by term

• Results publication: Morillo CA, Waskin H, Sosa-Estani S, Del Carmen Bangher M, Cuneo C, Milesi R, Mallagray M, Apt W, Beloscar J, Gascon J, Molina I, Echeverria LE, Colombo H, Perez-Molina JA, Wyss F, Meeks B, Bonilla LR, Gao P, Wei B, McCarthy M, Yusuf S; STOP-CHAGAS Investigators. Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial. J Am Coll Cardiol. 2017 Feb 28;69(8):939-947. doi: 10.1016/j.jacc.2016.12.023. PMID 28231946

• Medical Director, Study director, Merck Sharp & Dohme LLC