Study Will Evaluate the Relative Bioavailability, Safety, and Tolerability of Single Doses of Nifurtimox 30 mg Tablets Exhibiting Different in Vitro Dissolution Characteristics, and to Evaluate the Relative Bioavailability of Nifurtimox 30 mg and 120 mg

NCT03350295 | Completed Phase 1

• 1 other identifier: 16007
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Study to assess the relative Bioavailability To assess the relative bioavailability of three formulations of nifurtimox 30 mg tablets exhibiting different in vitro dissolution profiles To assess the pharmacokinetics (PK) of nifurtimox To investigate the safety and tolerability of nifurtimox.

Conditions

Chagas Disease

Keywords

Relative bioavailability; In vitro dissolution

Outcome Measures

Primary Outcomes (3)

• AUC(0-tlast) of nifurtimox

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

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

• Cmax of nifurtimox

  Cmax: Maximum observed drug concentration in measured matrix after single dose administration

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

• AUC of nifurtimox

  AUC: Area under the concentration versus time curve from zero to infinity after single (first) dose

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

Secondary Outcomes (4)

• Number of participants with adverse events

  up to 8 weeks

• AUC divided by dose: AUC/D

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

• AUC(0-tlast) divided by dose: AUC(0-tlast)/D

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

• Cmax divided by dose: Cmax/D

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

Study Arms (2)

GRP1 - Assess relative bioavailability(3-way cross-over)

EXPERIMENTAL

GROUP 1 (Treatments A, B, C) All 3 treatments in Group 1 consist of a dose of 120 mg nifurtimox (4 x 30 mg tablets). Participants received the 3 treatments in one of six treatment sequences under fed condition. Treatment A, dose administration with fast in vitro dissolution characteristics Treatment B, dose administration with medium in vitro dissolution characteristics Treatment C, dose administration with slow in vitro dissolution characteristics

Drug: Nifurtimox (Lampit, BAYA2502)

GRP2 - Assess relative bioavailability (2-way cross-over)

EXPERIMENTAL

GROUP 2 (Treatments D and E) Participants received the 2 treatments in one of two treatment sequences under fed condition. Treatment D, a single dose 30 mg nifurtimox dose with medium in vitro dissolution characteristics Treatment E, a single dose of 120 mg nifurtimox

Drug: Nifurtimox (Lampit, BAYA2502)

Interventions

Nifurtimox (Lampit, BAYA2502) DRUG

Oral Intake of 4 x 30 mg nifurtimox tablets for treatment A-C; Oral Intake of 1 x 30 mg nifurtimox tablets for treatment D Oral intake of 1 x 120 mg nifurtimox tablet for treatment E

GRP1 - Assess relative bioavailability(3-way cross-over); GRP2 - Assess relative bioavailability (2-way cross-over)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

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).
• Findings that would exclude the subject in the investigator's judgment, e.g. enlarged liver, irregular heartbeat, undiagnosed acute illness, and melanoma.
• Positive pregnancy test.
• Positive results for hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV 1+2).
• Positive urine drug screening..

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

FP Clinical Pharma

Buenos Aires, Ciudad Auton. de Buenos Aires, C1425BAB, 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 Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

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

Model Details: Group 1 ( Treatment A,B,C - 3 way cross-over), Group 2 ( Treatment D, E - 2 way cross over)

Study Record Dates

• First Submitted: November 9, 2017
• First Posted: November 22, 2017
• Study Start: June 14, 2018
• Primary Completion: September 18, 2018
• Study Completion: December 14, 2018
• Last Updated: December 12, 2019

Record last verified: 2019-12

Locations

AR (1)