Study to Assess the Food Effect on the Pharmacokinetics of Nifurtimox Tablets in Chronic Chagas' Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 21 November 2016
• Main ID: NCT02606864
• Date of registration: 16/11/2015
• Prospective Registration: Yes
• Primary sponsor: Bayer
• Public title: Study to Assess the Food Effect on the Pharmacokinetics of Nifurtimox Tablets in Chronic Chagas' Patients
• Scientific title: Non-blinded, Randomized, Single Center, Single Dose, Cross-over Study to Assess the Effect of a High Calorie/High Fat Meal on the Pharmacokinetics of Four 30 mg Nifurtimox Tablets Taken Orally by Adult Male and Female Patients Suffering From Chronic Chagas' Disease
• Date of first enrolment: December 2015
• Target sample size: 36
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02606864
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Argentina

Contacts

• Name: Bayer Study Director
• Affiliation: Bayer

Key inclusion & exclusion criteria

Inclusion Criteria:

- Study participants of reproductive potential must agree to utilize two reliable and
acceptable methods of contraception simultaneously when sexually active. One of these
methods must include a barrier method.

Subjects who are not of reproductive potential include: vasectomized males or
non-vasectomized males with documented azospermia prior to screening, as well as females
who are surgically sterilized with bilateral tubal ligation or who have undergone
hysterectomy. Women who are menopausal are also considered not of reproductive potential
if there has been no menses > 12 months prior to screening and supported by a
pre-screening follicle stimulating hormone (FSH) > 40 mIU/ml if available.

Examples of reliable and acceptable methods of birth control include, but are not limited
to: diaphragm with spermicide, condoms with spermicide or oral contraception with condom
use in the male partner. This applies from the signing of the informed consent up until 12
weeks after the last dose of the study medication.

- Male/female subject 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

- Age: 18 to 45 years (inclusive) at the first screening visit

- Body mass index (BMI): above/equal 18 and below/equal 29.9 kg / m²

Exclusion Criteria:

- Incompletely cured pre-existing diseases (except chronic Chagas) 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 drugs (active substances or excipients of the
preparations)

- Unstable or uncontrolled medical condition such as hypertension or diabetes,
decompensated heart failure, gastrointestinal (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
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) or Fridericia's Formula
(QTcF). (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 below 100 or above 140 mmHg (after resting in supine position
for a minimum of 3 min)

- Diastolic blood pressure below 50 or above 90 mmHg (after resting in supine position
for a minimum of 3 min)

- Pulse rate below 45 or above 95 beats / min (after resting in supine position for a
minimum of 3 min)

- Findings that would exclude the subject in the physician's judgment e.g. enlarged
liver, irregular heartbeat, undiagnosed acute illness, melanoma



Age minimum: 18 Years
Age maximum: 45 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Chagas Disease

Intervention(s)

Drug: Nifurtimox (BAYa2502)

Primary Outcome(s)

Plasma concentration of nifurtimox characterized by tmax [Time Frame: 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24 hours]

Area under the drug-concentration vs. time curve of nifurtimox from time 0 to the last data point[AUC(0-tlast)] [Time Frame: 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24 hours]

Plasma concentration nifurtimox characterized by Cmax [Time Frame: 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24 hours]

Plasma concentration of nifurtimox characterized by AUC [Time Frame: 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24 hours]

Secondary Outcome(s)

Number of participants with adverse events as a measure of safety and tolerability [Time Frame: Up to 8 weeks]

Secondary ID(s)

16005

Source(s) of Monetary Support

Please refer to primary and secondary sponsors