Chagas Disease
Conditions
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.
Interventions
DRUGPosaconazole
POS 40 mg/mL oral suspension
DRUGPlacebo for posaconazole
Placebo oral suspension
DRUGBenznidazole
BNZ 100 mg oral tablet
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Participant flow
Pre-assignment details
A total of 393 participants were screened, 123 were eligible for enrollment, and 120 were randomized
Participants by arm
| Arm | Count |
|---|---|
| Posaconazole POS 400 mg (10 mL) oral suspension twice daily for 60 days | 32 |
| Placebo POS placebo (10 mL) oral suspension twice daily for 60 days | 30 |
| Posaconazole + Benznidazole POS 400 mg (10 mL) oral suspension twice daily for 60 days and BNZ 100 mg oral tablet twice daily (200-mg daily dose) for 60 days | 28 |
| Benznidazole + Placebo BNZ 100 mg oral tablet twice daily (200-mg daily dose) for 60 days and POS placebo (10 mL) oral suspension twice daily for 60 days | 30 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Evidence of drug-induced hepatotoxicity | 0 | 1 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 7 | 6 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 4 |
| Overall Study | Serious adverse event | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Posaconazole | Placebo | Posaconazole + Benznidazole | Benznidazole + Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 40.3 years STANDARD_DEVIATION 8.6 | 42.2 years STANDARD_DEVIATION 7.8 | 40.2 years STANDARD_DEVIATION 8.4 | 40.4 years STANDARD_DEVIATION 7.7 | 40.8 years STANDARD_DEVIATION 8.1 |
| Sex: Female, Male Female | 16 Participants | 7 Participants | 13 Participants | 17 Participants | 53 Participants |
| Sex: Female, Male Male | 16 Participants | 23 Participants | 15 Participants | 13 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 32 | 8 / 30 | 18 / 28 | 21 / 30 |
| serious Total, serious adverse events | 1 / 32 | 1 / 30 | 2 / 28 | 3 / 30 |
Outcome results
Primary
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.
Time frame: Day 180
Population: The Full Analysis Population included all randomized subjects who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Posaconazole | Percentage of Participants With a Successful Response as Measured by Qualitative Polymerase Chain Reaction | 15.6 Percentage of participants |
| Placebo | Percentage of Participants With a Successful Response as Measured by Qualitative Polymerase Chain Reaction | 10.0 Percentage of participants |
| Posaconazole + Benznidazole | Percentage of Participants With a Successful Response as Measured by Qualitative Polymerase Chain Reaction | 82.1 Percentage of participants |
| Benznidazole + Placebo | Percentage of Participants With a Successful Response as Measured by Qualitative Polymerase Chain Reaction | 86.7 Percentage of participants |