| Eligibility |
Inclusion Criteria:
- Written informed consent must be provided before any study-specific tests or
procedures are performed.
- Male/female patient diagnosed with chronic Chagas' disease:
Previous diagnosis of acute or chronic Chagas' disease by a health clinic prior to
screening for the study. The diagnosis of chronic Chagas' disease may be made by clinical
findings, supported by antibody titers if available. If there is a known history of acute
disease, it is preferable to have documentation of parasites on the blood smear, if
available.
- Women and men of reproductive potential must agree to use adequate contraception when
sexually active. This applies for the time period between signing of the informed
consent form and 12 weeks after the last administration of study drug. The definition
of adequate contraception will be based on the judgment of the investigator and on
local requirements. Acceptable methods of contraception include, but are not limited
to: (i) condoms (male or female) with or without a spermicidal agent; (ii) diaphragm
or cervical cap with spermicide; (iii) intra-uterine device; (iv) hormone-based
contraception. Subjects must agree to utilize two reliable and acceptable methods of
contraception simultaneously.
- Women of childbearing potential with confirmed last menstrual period by anamnesis and
negative serum pregnancy test (beta-human chorionic gonadotropin [ßhCG]) at screening
and negative urine pregnancy test (ßhCG) at pre-dose of each treatment.
- Women of non-childbearing potential, such as surgically sterile women with either
written documentation of surgical sterility or negative serum pregnancy test (ßhCG) at
screening and negative urine pregnancy test (ßhCG) at pre-dose of each treatment.
- Male subjects who agree not to act as sperm donors for 12 weeks after last
administration of study drug.
- Age: 18 to 45 years (inclusive) at screening.
- Body mass index (BMI): =18 and <29.9 kg/m².
Exclusion Criteria:
- Incompletely cured pre-existing diseases (except chronic Chagas' disease without
active GI condition) for which it can be assumed that the absorption, distribution,
metabolism, elimination, and effects of the study drugs will not be normal.
- Acute Chagas' disease. (During the acute phase, the parasite on a blood smear may be
seen under a microscope. Different antibodies are present, depending on the course of
the disease).
- Known hypersensitivity to the study drug (active substance or excipients of the
preparations)
- Unstable or uncontrolled medical condition such as hypertension or diabetes,
decompensated heart failure, GI conditions that would interfere with the absorption of
the study drug (e.g. GI ulceration, peptic ulceration, GI bleeding, gastroesophageal
reflux, or other GI disease affecting gastroesophageal junction), conditions that
could potentially have an impact on drug metabolism or elimination (renal, hepatic
such as known hepatic or biliary abnormalities), or any clinically relevant active
infections in the opinion of the investigator within 4 weeks before the screening
visit, e.g. clinically relevant history or presence of significant respiratory (e.g.
interstitial lung disease), hematological, lymphatic, neurological, cardiovascular,
psychiatric, musculoskeletal, genitourinary, immunological, metabolic (e.g. diabetes),
and dermatological or connective tissue disease.
- Use of systemic or topical medicines or substances which oppose the study objectives
(including clinical treatment with nifurtimox and benznidazole) or which might
influence them within 4 weeks before the first study drug administration, e.g. an
investigational drug, any drug altering GI motility and/or gastric pH (e.g. antacids,
anticholinergic, para-sympatholytics), any drug known to induce liver enzymes (e.g.
dexamethasone, barbiturates, St. John's Wort [hypericum perforatum]), any drug known
to inhibit liver enzymes (e.g. ketoconazole, macrolides).
- Clinically relevant findings in the ECG such as a second- or third-degree
atrioventricular block, prolongation of the QRS complex over 120 msec or of the QT
interval over 450 msec using Bazett's formula (QTcB). (Clinically stable subjects with
Chagas'-related heart disease and pacemaker in place for >1 year and evaluated by a
cardiologist =6 months before the first dose of study drug will not be excluded.)
- Systolic blood pressure <100 or >140 mmHg (after resting in supine position for a
minimum of 3 minutes).
- Diastolic blood pressure <50 or >90 mmHg (after resting in supine position for a
minimum of 3 minutes).
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