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

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ClinicalTrials.gov Identifier: NCT03334838
Recruitment Status : Recruiting
First Posted : November 7, 2017
Last Update Posted : November 15, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE November 3, 2017
First Posted Date  ICMJE November 7, 2017
Last Update Posted Date November 15, 2019
Actual Study Start Date  ICMJE June 10, 2019
Estimated Primary Completion Date November 29, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 3, 2017)
  • AUC(0-tlast) of nifurtimox [ Time Frame: 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour ]
    Area under the drug-concentration vs. time curve of nifurtimox from time 0 to the last data point[AUC(0-tlast)]
  • Cmax of nifurtimox [ Time Frame: 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour ]
    Peak concentrations (Cmax) of the plasma concentration vs time profiles
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03334838 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 3, 2017)
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to 8 weeks ]
    Clinical Laboratory Test, physical examinations, vital signs and 12 electrocardiograms ( ECG's) for safety and tolerability
  • AUC(0-tlast) divided by dose: AUC(0-tlast)/D [ Time Frame: 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour ]
  • Cmax divided by dose: Cmax/D [ Time Frame: 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Assess the Food Effect on the Pharmacokinetics of Nifurtimox Tablets in Chronic Chagas' Patients - Dietary Habits Study
Official Title  ICMJE Open-label, Randomized, Single-dose, Cross-over Study to Evaluate the Influence of Dietary Habits on the Pharmacokinetics, Safety, and Tolerability of a 120 mg Dose and to Assess the Relative Bioavailability of a 240 mg Dose of Nifurtimox Tablets Administered to Adult Male and Female Patients With Chagas' Disease
Brief Summary This study will evaluate the effect of food on the absorption of the drug as well as safety and tolerability in adults suffering from chronic Chagas' disease In addition pharmacokinetics of the drug following 120 and 240 mg single doses will be assessed
Detailed Description

Primary objective is to evaluate the effect of various food compositions on the PK of nifurtimox after a single oral dose (120 mg) administered under 3 types of fed conditions (low fat, dairy products, and high calorie and high fat), as well as fasted conditions, to assess relative bioavailability.It was chosen to allow a direct inter-study comparison of PK data obtained in previous studies.

A secondary objective of the study is to assess the relative bioavailability of 2 different dose levels of nifurtimox, given as a single oral dose, in a second group of patients.The second treatment group addresses a biopharmaceutical aspect for which no study data have been obtained to date. In order to assess the relationship between dose and exposure (linearity of PK), an analysis of the dose range of 120 mg to 240 mg was chosen to close the knowledge gap for this dose range.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chagas' Disease
Intervention  ICMJE Drug: Nifurtimox (Lampit, BAYA2502)
Oral Intake of 4 x 30 mg nufurtimox tablets for treatment A-D; Oral Intake of 8 x 30 mg nufurtimox tablets for treatment E.
Study Arms  ICMJE
  • Experimental: GRP 1 - Assess relative bioavailability (4-way crossover)

    GROUP 1 (Treatments A, B, C, D) All treatments in Group 1 consist of a dose of 120 mg nifurtimox (4 x 30 mg tablets).

    In Treatment A, dose administration will be in a fasted state.

    For the other treatments, dose administration will be in a fed state:

    Treatment B after a low-fat breakfast; Treatment C after a breakfast consisting of dairy products (yogurt+milk); and Treatment D after a high-calorie and high-fat breakfast.

    Intervention: Drug: Nifurtimox (Lampit, BAYA2502)
  • Experimental: GRP 2 - Assess relative bioavailability (2-way crossover)

    All subjects in Group 2 will receive a single dose of nifurtimox in each of the Treatments D and E.

    In Treatment D, subjects will receive 120 mg nifurtimox (4 x 30 mg tablets), and in Treatment E, subjects will receive 240 mg nifurtimox (8 x 30 mg tablets). Both treatments will be administered in a fed state, after a high-calorie and high-fat breakfast.

    Intervention: Drug: Nifurtimox (Lampit, BAYA2502)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 3, 2017)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2020
Estimated Primary Completion Date November 29, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 [βhCG]) at screening and negative urine pregnancy test (βhCG) 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 (βhCG) at screening and negative urine pregnancy test (βhCG) 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Bayer Clinical Trials Contact (+) 1-888-8422937 clinical-trials-contact@bayer.com
Contact: For trial location information (Phone Menu Options '3' or '4') (+)1-888-84 22937
Listed Location Countries  ICMJE Argentina
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03334838
Other Study ID Numbers  ICMJE 16006
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Bayer
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP