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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01927224
First received: August 20, 2013
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

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).


Condition Intervention Phase
Chagas Disease
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)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Area under the drug-concentration vs. time curve of nifurtimox from time 0 to the last data point [AUC(0-tn)] [ Time Frame: 0-24 hours ] [ Designated as safety issue: No ]
  • Maximum drug concentration of nifurtimox in plasma (Cmax) [ Time Frame: Up to 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 37
Study Start Date: November 2013
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01927224

Locations
Argentina
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1425BAB
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01927224     History of Changes
Other Study ID Numbers: 16004
Study First Received: August 20, 2013
Last Updated: June 6, 2014
Health Authority: Argentina: National Administration of Drugs, Food & Medical Technology (ANMAT)

Additional relevant MeSH terms:
Chagas Disease
Trypanosomiasis
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Nifurtimox
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014