Trypanosomiasis, AfricanPhase 1NCT02571062
Bioequivalence Study - Reference Clinical Fexinidazole Tablet Versus Proposed Market Formulation
A Phase 1 study testing Fexinidazole in people with Trypanosomiasis, African, run by Drugs for Neglected Diseases at 1 site in France.
Trial summary
Phase 1 bioequivalence (BE) study. This study is for regulatory purpose to determine BE of the tablet formulation used in the clinical trials and the final marketed tablet formulation under fed condition. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Trypanosomiasis, African
- What is being tested?
- Fexinidazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2015to Jun 2015
- 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
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- All subjects to be of sub-Saharan African origins with both parents of sub- Saharan African origins too;
- Signed ICF;
- 18 to 45 years old
- Male subjects with a BMI calculated as weight (kg)/height (m)2 from 18 to 28 kg/m2 at screening
- Light smokers (less than 5 cigarettes per day, or equivalent e-cigarettes or nicotine patch) or subjects who are non-smokers. No smoking (or use of smoking substitute e.g. nicotine patch) is permitted from screening throughout the study;
- Normal arterial BP and pulse rate or, if abnormal, considered not clinically significant by the principal Investigator. These will be measured after resting for 5 min;
- Normal ECG or, if abnormal, considered not clinically significant by the principal Investigator;
- Registered with the French Social Security in agreement with the French law on biomedical experimentation.
Who cannot join
- Who on direct questioning and physical examination have evidence of any clinically significant acute or chronic disease, including known or suspected HIV, HBV or HCV infection
- With any clinically significant abnormality following review of pre-study laboratory tests (ASAT, ALAT) must be within normal ranges), vital signs, full physical examination and ECG;
- Who are within the exclusion period defined in the National Register for Healthy Volunteers of the French Ministry of Health;
- Unwilling to give their informed consent;
- Who have a positive laboratory test for Hepatitis B surface antigen (HbsAg), or anti-HIV 1/2 or anti- HCV antibodies;
- Who have a history of allergy, intolerance or photosensitivity to any drug;
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- Who have a history of serious allergy, asthma, allergic skin rash or sensitivity to any drug;
- Who have a history of HAT;
- Who are known or suspected alcohol or drug abusers (more than 14 units of alcohol per week, one unit = 8 g or about 10 mL of pure alcohol);
- Who have a positive alcohol breath test
- Who drink more than 8 cups daily of beverage containing caffeine;
- Who have a positive laboratory test for urine drug screening (opiates, cocaine, amphetamine, cannabis, benzodiazepines);
- Who have undergone surgery or have donated blood within 12 weeks prior to the start of the study;
- Who have taken any prescribed or over the counter drug (including antacid drug), with the exception of paracetamol (up to 3 g per day) within 2 weeks prior to the first dose administration;
- Who have already taken fexinidazole;
- Who have any clinical condition or prior therapy which, in the opinion of the Investigator, made the subject unsuitable for the study;
- Who participated to any clinical trial with an investigational drug in the past 3 months preceding the first study drug administration.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Bioequivalence Study of the Reference Clinical Fexinidazole Tablet vs Proposed Market Formulation in Healthy Male Volunteers of African Sub-Saharan Origin:an Open-label,Randomized,Two-treatment,Single Dose,Replicate Design,Fed Condition
Phase 1 bioequivalence (BE) study. This study is for regulatory purpose to determine BE of the tablet formulation used in the clinical trials and the final marketed tablet formulation under fed condition.
The study will be an open-label, 2-treatment, 2-sequence, 4-period, single-dose, replicate crossover study under fed condition. The 4-period sequences for the replicate design will be TRTR and RTRT, where R designates the reference formulation and T the test formulation. Subject will be allocated randomly to one of the two sequences of treatments according to the randomization list.
Read the detailed description
Ideally, BE study should be conducted under fasting condition as this is considered to be the most sensitive condition to detect a potential difference between formulations. However as fexinidazole is recommended to be taken with food, as food increased the plasma concentration by 2.5 to 3 fold compared to plasma. BE will be conducted under fed condition, using field adapted meal. The wash-out period should be sufficient to ensure that drug concentrations are below the limit of quantification in all the subjects at the beginning of the next period, a 2 weeks wash-out period will be used. The intra-subject variability of fexinidazole was evaluated based on a previous 3-period cross-over study (1) and was estimated at 25%. As this value was quite high and close to 30%, a replicate design was chosen.
Primary objective:
To assess BE of the clinical trial 600 mg tablet formulation versus (vs.) the proposed market 600 mg tablet formulation of fexinidazole under fed condition after single oral administration of 1200 mg.
Secondary objectives:
To assess the pharmacokinetic profile of the two metabolites fexinidazole sulfoxide and fexinidazole sulfone under the fed condition. To assess the safety and tolerability in healthy volunteers under the same study conditions.
Meal: On each treatment period, fexinidazole will be given with concomitant meal which composition will be as close as possible to field condition
sample size: In order to have 24 evaluable subjects a total of 30 subjects will be recruited in the study.
Study Treatment: Single oral dose of 1200 mg / period :
- Treatment R: Reference formulation, i.e. 2 × 600 mg clinical tablets
- Treatment T: Test formulation, i.e. 2 × 600 mg proposed market tablets
Pharmacokinetic sampling: Pre-dose, and 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 120 and 168 h post-dose Total blood drawn: 390 mL ( Pharmacokinetic = 240 mL + safety = 150 mL)
- Conditions
- Trypanosomiasis, African
- Being tested
- Fexinidazole
- Keywords
- bioequivalence
- Medical subject headings
- Trypanosomiasis, African
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FexinidazoleDrug
| Study group | Role | What they receive |
|---|---|---|
| experimental formulation | Experimental | crossover design Receives: Drug: Fexinidazole |
| final formulation | Experimental | crossover design Receives: Drug: Fexinidazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic parameters of fexinidazole following single dose
Area Under the Curve (AUC)
Measured: Pharmacokinetic sampling: Pre-dose, and 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 120 and 168 h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2015 (estimated)
- Study startMar 2015
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Trypanosomiasis, AfricanStudies of the same condition, open and under way.
- 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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antoine Tarral, MD, Study director, Drugs for Neglected Diseases
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02571062
- Sponsor's protocol ID
- DNDiHATFEX008
- Status last verified
- Jun 2015
- First submitted
- 24 Jun 2015
- Last updated
- 8 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Bioequivalence Study of the Reference Clinical Fexinidazole Tablet vs Proposed Market Formulation in Healthy Male Volunteers of African Sub-Saharan Origin:an Open-label,Randomized,Two-treatment,Single Dose,Replicate Design,Fed Condition
- ClinicalTrials.gov ID
- NCT02571062
- Acronym / sponsor ID
- DNDiHATFEX008
- Conditions
- Trypanosomiasis, African
- Keywords
- bioequivalence
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 8 Oct 2015 (estimated)
- 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.
Phase 1 bioequivalence (BE) study. This study is for regulatory purpose to determine BE of the tablet formulation used in the clinical trials and the final marketed tablet formulation under fed condition.
The study will be an open-label, 2-treatment, 2-sequence, 4-period, single-dose, replicate crossover study under fed condition. The 4-period sequences for the replicate design will be TRTR and RTRT, where R designates the reference formulation and T the test formulation. Subject will be allocated randomly to one of the two sequences of treatments according to the randomization list.
Detailed description
Ideally, BE study should be conducted under fasting condition as this is considered to be the most sensitive condition to detect a potential difference between formulations. However as fexinidazole is recommended to be taken with food, as food increased the plasma concentration by 2.5 to 3 fold compared to plasma. BE will be conducted under fed condition, using field adapted meal. The wash-out period should be sufficient to ensure that drug concentrations are below the limit of quantification in all the subjects at the beginning of the next period, a 2 weeks wash-out period will be used. The intra-subject variability of fexinidazole was evaluated based on a previous 3-period cross-over study (1) and was estimated at 25%. As this value was quite high and close to 30%, a replicate design was chosen.
Primary objective:
To assess BE of the clinical trial 600 mg tablet formulation versus (vs.) the proposed market 600 mg tablet formulation of fexinidazole under fed condition after single oral administration of 1200 mg.
Secondary objectives:
To assess the pharmacokinetic profile of the two metabolites fexinidazole sulfoxide and fexinidazole sulfone under the fed condition. To assess the safety and tolerability in healthy volunteers under the same study conditions.
Meal: On each treatment period, fexinidazole will be given with concomitant meal which composition will be as close as possible to field condition
sample size: In order to have 24 evaluable subjects a total of 30 subjects will be recruited in the study.
Study Treatment: Single oral dose of 1200 mg / period :
- Treatment R: Reference formulation, i.e. 2 × 600 mg clinical tablets
- Treatment T: Test formulation, i.e. 2 × 600 mg proposed market tablets
Pharmacokinetic sampling: Pre-dose, and 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 120 and 168 h post-dose Total blood drawn: 390 mL ( Pharmacokinetic = 240 mL + safety = 150 mL)
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| experimental formulation | Experimental | Drug: Fexinidazolecrossover design |
| final formulation | Experimental | Drug: Fexinidazolecrossover design |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- All subjects to be of sub-Saharan African origins with both parents of sub- Saharan African origins too;
- Signed ICF;
- 18 to 45 years old
- Male subjects with a BMI calculated as weight (kg)/height (m)2 from 18 to 28 kg/m2 at screening
- Light smokers (less than 5 cigarettes per day, or equivalent e-cigarettes or nicotine patch) or subjects who are non-smokers. No smoking (or use of smoking substitute e.g. nicotine patch) is permitted from screening throughout the study;
Key exclusion criteria (17 listed)
- Who on direct questioning and physical examination have evidence of any clinically significant acute or chronic disease, including known or suspected HIV, HBV or HCV infection
- With any clinically significant abnormality following review of pre-study laboratory tests (ASAT, ALAT) must be within normal ranges), vital signs, full physical examination and ECG;
- Who are within the exclusion period defined in the National Register for Healthy Volunteers of the French Ministry of Health;
- Unwilling to give their informed consent;
- Who have a positive laboratory test for Hepatitis B surface antigen (HbsAg), or anti-HIV 1/2 or anti- HCV antibodies;
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 |
|---|---|---|
| Fexinidazole | Drug | experimental formulation, final formulation |
Primary outcome
Pharmacokinetic parameters of fexinidazole following single dose
Time frame: Pharmacokinetic sampling: Pre-dose, and 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 120 and 168 h
Area Under the Curve (AUC)
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 8 Oct 2015.
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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.
Antoine Tarral, MD study director
Drugs for Neglected Diseases
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 Fexinidazole in people with Trypanosomiasis, African, run by Drugs for Neglected Diseases at 1 site in France.
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 8 inclusion and 17 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 8 Oct 2015. 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 France. 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?
Pharmacokinetic parameters of fexinidazole following single dose (time frame: Pharmacokinetic sampling: Pre-dose, and 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 120 and 168 h). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Oct 2015.