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

NCT03334838 | Completed Phase 1

• 1 other identifier: 16006
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluated 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

Conditions

Chagas' Disease

Keywords

Food effect; Dose proportionality

Outcome Measures

Primary Outcomes (2)

• AUC(0-tlast) of nifurtimox (evaluation of food effect)

  Area under the drug-concentration vs. time curve of nifurtimox from time 0 to the last data point\[AUC(0-tlast)\]

  0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour

• Cmax of nifurtimox (evaluation of food effect)

  Peak concentrations (Cmax) of the plasma concentration vs time profiles

  0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour

Secondary Outcomes (3)

• Number of participants with treatment-emergent adverse events (TEAEs)

  Up to 8 weeks

• AUC(0-tlast)/D of nifurtimox (evaluation of food effect)

  0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour

• Cmax/D of nifurtimox (evaluation of food effect)

  0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour

Study Arms (2)

GRP 1 - Assess relative bioavailability (4-way crossover)

EXPERIMENTAL

GROUP 1 (Treatments A, B, C, D) All treatments in Group 1 consisted of a dose of 120 mg nifurtimox (4 x 30 mg tablets). In Treatment A, dose administration was in a fasted state. For the other treatments, dose administration was 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.

Drug: Nifurtimox (Lampit, BAYA2502)

GRP 2 - Assess relative bioavailability (2-way crossover)

EXPERIMENTAL

All subjects in Group 2 received a single dose of nifurtimox in each of the Treatments D and E. In Treatment D, subjects received 120 mg nifurtimox (4 x 30 mg tablets), and in Treatment E, subjects received 240 mg nifurtimox (8 x 30 mg tablets). Both treatments were administered in a fed state, after a high-calorie and high-fat breakfast.

Drug: Nifurtimox (Lampit, BAYA2502)

Interventions

Nifurtimox (Lampit, BAYA2502) DRUG

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.

GRP 1 - Assess relative bioavailability (4-way crossover); GRP 2 - Assess relative bioavailability (2-way crossover)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

FP Clinical Pharma

Buenos Aires, Ciudad Auton. de Buenos Aires, C1431CEF, Argentina

Location

Related Publications (1)

• Stass H, Just S, Weimann B, Ince I, Willmann S, Feleder E, Freitas C, Yerino G, Munster U. Clinical investigation of the biopharmaceutical characteristics of nifurtimox tablets - Implications for quality control and application. Eur J Pharm Sci. 2021 Nov 1;166:105940. doi: 10.1016/j.ejps.2021.105940. Epub 2021 Jul 12.

  PMID: 34265407 DERIVED

Related Links

• Click here to find results for studies related to Bayer products

MeSH Terms

Conditions

Chagas Disease

Interventions

Nifurtimox

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Nitrofurans; Nitro Compounds; Organic Chemicals; Thiazines; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2017
• First Posted: November 7, 2017
• Study Start: June 10, 2019
• Primary Completion: November 7, 2019
• Study Completion: January 29, 2020
• Last Updated: December 30, 2020

Record last verified: 2020-12

Locations

AR (1)