Chagas' DiseasePhase 1NCT03334838
Study to Assess the Food Effect on the Pharmacokinetics of Nifurtimox Tablets in Chronic Chagas' Patients - Dietary Habits Study
A Phase 1 study testing Nifurtimox (Lampit, BAYA2502) in people with Chagas' Disease, run by Bayer at 1 site in Argentina.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Chagas' Disease
- What is being tested?
- Nifurtimox (Lampit, BAYA2502)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteArgentina
- Study dates
- 10 Jun 2019to 29 Jan 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
Argentina1 site
FP Clinical Pharma
Buenos Aires, Ciudad Auton. de Buenos Aires, C1431CEF
About this study
Official title: 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
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
Read the detailed description
Primary objective was 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 was 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 addressed 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.
- Conditions
- Chagas' Disease
- Being tested
- Nifurtimox (Lampit, BAYA2502)
- Keywords
- Food effect, Dose proportionality
- Medical subject headings
- Chagas Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Nifurtimox (Lampit, BAYA2502) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)]
Measured: 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
Measured: 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)
Clinical Laboratory Test, physical examinations, vital signs and 12 electrocardiograms ( ECG's) for safety and tolerability
Measured: Up to 8 weeks
AUC(0-tlast)/D of nifurtimox (evaluation of food effect)
AUC(0-tlast)/D: AUC(0-tlast) divided by dose
Measured: 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)
Cmax/D: Cmax divided by dose
Measured: 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2017
- Study start10 Jun 2019
- Primary completion7 Nov 2019
- Study completion29 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chagas' DiseaseStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03334838
- Sponsor's protocol ID
- 16006
- Status last verified
- Dec 2020
- First submitted
- 3 Nov 2017
- Last updated
- 30 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 34265407
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03334838
- Acronym / sponsor ID
- 16006
- Conditions
- Chagas' Disease
- Keywords
- Food effect, Dose proportionality
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 10 Jun 2019 (actual)
- Primary completion
- 7 Nov 2019 (actual)
- Study completion
- 29 Jan 2020 (actual)
- First posted
- 7 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Primary objective was 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 was 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 addressed 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GRP 1 - Assess relative bioavailability (4-way crossover) | Experimental | Drug: Nifurtimox (Lampit, BAYA2502)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. |
| GRP 2 - Assess relative bioavailability (2-way crossover) | Experimental | Drug: Nifurtimox (Lampit, BAYA2502)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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (8 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | GRP 1 - Assess relative bioavailability (4-way crossover), GRP 2 - Assess relative bioavailability (2-way crossover) |
Primary outcome
AUC(0-tlast) of nifurtimox (evaluation of food effect)
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 (evaluation of food effect)
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
3 secondary outcomes
Number of participants with treatment-emergent adverse events (TEAEs)
Time frame: Up to 8 weeks
AUC(0-tlast)/D of nifurtimox (evaluation of food effect)
Time frame: 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)
Time frame: 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2020.
- Derived from this study: PubMed 34265407Stass 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.
Related trials for Chagas' Disease
Not yet recruitingObservational study
Assessment of the Risk of Zoonotic Infections in Prisons in French Guiana
Q Fever, Leptospirosis
RecruitingPhase 2
A Study of Efficacy, Safety, Tolerability of LXE408 in Participants With Chronic Chagas Disease.
Chagas Disease
Recruiting
Cardiac Contractility Modulation in Chagas Heart Disease
Chagas Cardiomyopathy, Heart Failure
Not yet recruitingObservational study
An Observational Pregnancy Safety Study in Women Who Were Exposed to the Drug Nifurtimox During Pregnancy to Learn About the Risk of Pregnancy Complications and About the Mother's and Baby's Health
Chagas Disease
Active, not recruitingPhase 3
Prospective Study of Benznidazole for Chagas' Disease Children With Chronic Indeterminate Chagas Disease
Chagas Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nifurtimox (Lampit, BAYA2502) in people with Chagas' Disease, run by Bayer at 1 site in Argentina.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC(0-tlast) of nifurtimox (evaluation of food effect) (time frame: 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03334838, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2020.