Study to Assess Bioequivalence of 30 and 120 mg Nifurtimox Tablets in Chronic Chagas' Patients

Open Label, Randomized, Single Dose Cross-over Study to Assess Bioequivalence Between Single 120 mg Nifurtimox Tablet and Four 30 mg Nifurtimox Tablets Administered Orally, Following High Calorie/High Fat Meal to Adult Male and Female Patients Suffering From Chronic Chagas' Disease and to Determine the Pharmacokinetics of Nifurtimox Tablets Administered Orally, in a Form of Aqueous Slurry

This study will evaluate the bioequivalence as well as safety and tolerability of a novel 30 mg tablet of nifurtimox compared to the corresponding marketed 120 mg tablet in adult subjects suffering from chronic Chagas' disease when administered after a high-fat / high-calorie test meal. This study is a necessary step for the development of an age appropriate pediatric oral dosage form for the treatment of Chagas' disease in endemic countries according to the recommendations provided by current international guidelines (EMA Guideline on Clinical Development of Medicinal Products, EMA Note for Guidance on Oral Dosage Forms).

Study Overview

• Status: Completed
• Conditions: Chagas Disease
• Intervention / Treatment: Drug: Nifurtimox (BAYa2502) (4 x 30 mg tablet); Drug: Nifurtimox (BAYa2502) (slurry of 4 x 30 mg tablets in tap water); Drug: Nifurtimox (BAYa2502) (120 mg tablet)

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Auton. de Buenos Aires
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1425BAB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Upon consent, women of childbearing potential must use 2 forms of highly effective contraception for the duration of the study and for 12 weeks after the last drug administration. The definition of highly effective contraception will be left at the discretion of the investigator and will be in line with ICH Topic M 3 (R2): Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals
• Male subjects who are sterile, not sexually active or agree to use 2 forms of highly effective contraception during the study and for 12 weeks after receiving the study drug. The definition of highly effective contraception will be left at the discretion of the investigator and will be in line with ICH ICH Topic M 3 (R2): Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals
• 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 ar 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 gastrointestinal 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 electrocardiogram (ECG) such as a second- or third-degree AV block, prolongation of the QRS complex over 120 msec or of the QTc-interval over 450 msec
• Systolic blood pressure below 100 or above 140 mmHg (after at least 15 min supine)
• Diastolic blood pressure below 50 or above 90 mmHg (after at least 15 min supine)
• Heart rate below 45 or above 95 beats / min (after at least 15 min supine)
• Findings that would exclude the subject in the physician's judgment e.g. enlarged liver, irregular heartbeat, undiagnosed acute illness, melanoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Nifurtimox (Group 1); Descriptive pharmacokinetic group	Drug: Nifurtimox (BAYa2502) (4 x 30 mg tablet); 120 mg single dose as four 30 mg tablets after a high fat, high calorie meal; Drug: Nifurtimox (BAYa2502) (slurry of 4 x 30 mg tablets in tap water); 120 mg single dose as aqueous slurry in tap water produced from four 30 mg tablets; ingestion after a high fat, high calorie meal
EXPERIMENTAL: Nifurtimox (Group 2); The assessment of bioequivalence of the two formulation (30mg vs.120mg)	Drug: Nifurtimox (BAYa2502) (4 x 30 mg tablet); 120 mg single dose as four 30 mg tablets after a high fat, high calorie meal; Drug: Nifurtimox (BAYa2502) (120 mg tablet); 120 mg single dose as one 120 mg tablet after a high fat, high calorie meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the drug-concentration vs. time curve of nifurtimox from time 0 to the last data point [AUC(0-tn)]	0-24 hours
Maximum drug concentration of nifurtimox in plasma (Cmax)	Up to 24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events as a measure of safety and tolerability	Up to 8 weeks

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): September 1, 2014

Study Registration Dates

• First Submitted: August 20, 2013
• First Submitted That Met QC Criteria: August 20, 2013
• First Posted (ESTIMATE): August 22, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): October 16, 2015
• Last Update Submitted That Met QC Criteria: October 14, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Trypanosomiasis; Euglenozoa Infections; Chagas Disease; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Trypanocidal Agents; Nifurtimox
• Other Study ID Numbers: 16004