Brain Neoplasms, Malignant, PrimaryPhase 4NCT02343081
Bioequivalence Study of Temozolomide in Patients With Primary Tumors of the Central Nervous System
A Phase 4 study testing Temozolomide in people with Brain Neoplasms, Malignant, Primary, run by Monte Verde SA at 2 sites in Argentina.
Trial summary
The purpose of this crossover, single-dose, bioequivalence study is to compare the rate and extent of absorption of Temozolomide after the administration of the study product (Dralitem®, Monte Verde S.A.) and the reference product (Temodal®, Schering Plough) in primary Central Nervous System patients. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Brain Neoplasms, Malignant, Primary
- What is being tested?
- Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesArgentina
- Study dates
- Jan 2012to Oct 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients with primary malignant tumors of the central nervous system (CNS) excluding subjects with primary CNS lymphoma.
- Age> 21 years.
- There should be a gap of two weeks between the last surgery and/or radiotherapy procedure and the day of randomization. If the procedure were intrabdominal, the gap should be of four weeks.
- Patients with neutrophils> 1.5 x 109 / L and platelets> 100 x 109 / L.
- Signed written informed consent for participation in the trial.
Who cannot join
- Known hypersensitivity to Temozolomide or any other ingredient of the pharmaceutical formulation.
- Any situation (eg. vomiting) that may interfere with the absorption of the product under study.
- Chemotherapy or biological therapy within four weeks prior to administering the products under study.
- Patients who experience any symptoms of toxicity to prior antineoplastic therapies upon administration of the products under study.
- Participation in other clinical research studies during the 90 days before the start of this study.
- History of alcohol or drugs abuse.
Show all 10Show fewer
- History of severe allergic reactions to any type of antigen.
- History of gastrointestinal surgery (except uncomplicated appendectomy, of at least three months old).
- Patients whose clinical status would affect the safety of the products under study or interfere with the pharmacokinetic evaluation, at the discretion of the investigator.
- Pregnant women or women planning to become pregnant during the study.
Trial locations and contacts
2 sites in 1 country.
Argentina2 sites
FLENI Instituto de Rehabilitación y Educación Terapéutica
Belen de Escobar, Buenos Aires, B1625XAS
FLENI Instituto Clínico-Quirúrgico de Diagnóstico y Tratamiento
Ciudad Autónoma de Buenos Aires, Buenos Aires, C1428AQK
About this study
Official title: A Randomized, Open Label, Two-way Crossover, Single Dose Bioequivalence Study Comparing Dralitem® Capsules to the Reference Drug Temodal® Capsules in Patients With Primary Tumors of the Central Nervous System Under Fasting Conditions
The purpose of this crossover, single-dose, bioequivalence study is to compare the rate and extent of absorption of Temozolomide after the administration of the study product (Dralitem®, Monte Verde S.A.) and the reference product (Temodal®, Schering Plough) in primary Central Nervous System patients.
Read the detailed description
Prospective, randomized, two-period, two treatment, two-way crossover bioequivalence study of two Temozolomide oral formulations (Dralitem vs. Temodal), in primary Central Nervous System tumor patients under fasting conditions. Open label to the patients and investigators and blind to the bioanalytical and clinical laboratories.
Study plan: days -21 to 0 (Recruitment period); days 1 to 5 (Treatment period); days 6 to 21 (Safety surveillance period). Sample size: 24 patients will be randomized. The patients will be administered Temozolomide 200 mg/m2 on the first two days (Dralitem) of the treatment cycle.
They will be admitted to the study clinical site on the evening of day 2. In the morning of day 3 they will be randomized into two groups of equal size. According to the assigned random number, each subject will receive a single oral dose of Temozolomide 200mg/m2 from either Monte Verde Sociedad Anónima (SA) product (Dralitem) or from Schering-Plough product (Temodal). The single dose of 200 mg/m2 will be reached with three different Temozolomide capsule strengths: 20, 100 and 250 mg. Drugs will be administered with 200-240 ml of water in semi-sitting upright position.
The following day (day 4) each subject will receive an oral dose of Temozolomide 200 mg/m2 of the product that did not receive the day before. On days 3 and 4 after drug administration, blood samples will be obtained for pharmacokinetic evaluation. The patient will be discharged from the clinical site on day 4 after completion of sampling for pharmacokinetic analysis. On day 5, all patients will receive Temozolomide 200 mg/m2 (Dralitem).
On days 3 and 4, samples of venous blood will be withdrawn from the forearm vein of each volunteer at the following time points: 0 (pre-dose) and 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 hours post-dose after each period administration. The washout period between the treatment arms was 10 hours, on days 3 and 4. Samples will be processed according to the validated method MANA (Método Analítico) - PLB (Proyecto Laboratorio Bioanalítico) 004 - TEM (Temozolomide) - 01/01. Measurement of plasma concentration of Temozolomide was performed using High Performance Liquid Chromatography (HPLC) followed by detection by tandem mass spectrometry (MS / MS).
The area under the curve (AUC) and the Cmax levels of the drug vs. time will be obtained for each subject. The resulting values of the logarithmic transformation of these parameters will be used for statistical comparisons (mixed effects ANOVA). The limits of the 90% confidence interval for the ratio of log transformed pharmacokinetic parameters will be calculated. Bioequivalence criteria: each calculated confidence interval should be within the acceptance range from 80.00 to 125.00.
- Conditions
- Brain Neoplasms, Malignant, Primary
- Being tested
- Temozolomide
- Keywords
- brain neoplasm, bioequivalence, temozolomide
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called Temodal
TemozolomideDrug
Also called Dralitem
| Study group | Role | What they receive |
|---|---|---|
| Temodal | Active comparator | Temozolomide (Schering-Plough) 200 mg/m2, single oral dose. Receives: Drug: Temozolomide |
| Dralitem | Experimental | Temozolomide (Monte Verde S.A.) 200 mg/m2, single oral dose Receives: Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax
Rate of absorption of Temozolomide (Cmax) will be measured after the oral administration of the test product (Dralitem®, Monte Verde S.A.) or the reference product (Temodal®, Schering-Plough).
Measured: 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 hours on Days 3 and 4
AUC0-t
Extent of absorption of Temozolomide from time (0) to the last quantifiable concentration (t) will be measured after the oral administration of the test product (Dralitem®, Monte Verde S.A.) or the reference product (Temodal®, Schering-Plough)
Measured: 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 hours on Days 3 and 4
AUC0-∞
Extent of absorption of Temozolomide from time (0) to infinity (∞) will be measured after oral administration of the test product (Dralitem®, Monte Verde S.A.) or the reference product (Temodal®, Schering-Plough).
Measured: 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 hours on Days 3 and 4
Secondary outcomes (1)
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs and SAEs will be collected from the start of study treatment and until two weeks post last dose. If AEs or SAEs extend in time and are not resolved before the end of the 2-week follow up period, this period shall last until the event/s are resolved.
Measured: Up to two weeks post last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2015 (estimated)
- Study startJan 2012
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain Neoplasms, Malignant, PrimaryStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Monte Verde SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- FLENI Instituto de Rehabilitación y Educación Terapéutica, BA, Argentina., Bioanalytical Unit, Laboratorio Raffo S.A., BA, Argentina., FLENI Multi-Specialty Research Center, BA, Argentina.
- Responsible party
- Sponsor
- Investigators
- Alejandro D Muggeri, Physician, Principal investigator, FLENI Instituto Clínico-Quirúrgico de Diagnóstico y Tratamiento
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02343081
- Sponsor's protocol ID
- RFF -0208
- Status last verified
- Mar 2015
- First submitted
- 7 Jan 2015
- Last updated
- 2 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Muggeri A, Vago M, Perez S, Rubio M, Gonzalez C, Magarinos C, Rosenberg M, Costa F, Perez-Lloret S. A Randomized, Open-Label, Two-Way Crossover, Single-Dose Bioequivalence Study of Temozolomide 200 mg/m2 (Dralitem(R) vs. Temodal(R) Capsules) in Patients with Primary Tumors of the Central Nervous System Under Fasting Conditions. Drugs R D. 2017 Sep;17(3):427-434. doi: 10.1007/s40268-017-0199-3.
PubMed 28756607
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open Label, Two-way Crossover, Single Dose Bioequivalence Study Comparing Dralitem® Capsules to the Reference Drug Temodal® Capsules in Patients With Primary Tumors of the Central Nervous System Under Fasting Conditions
- ClinicalTrials.gov ID
- NCT02343081
- Acronym / sponsor ID
- RFF -0208
- Conditions
- Brain Neoplasms, Malignant, Primary
- Keywords
- brain neoplasm, bioequivalence, temozolomide
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Monte Verde SAIndustry (pharma, biotech, devices)
- Collaborators
- FLENI Instituto de Rehabilitación y Educación Terapéutica, BA, Argentina., Bioanalytical Unit, Laboratorio Raffo S.A., BA, Argentina., FLENI Multi-Specialty Research Center, BA, Argentina.
- Study start
- Jan 2012
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 21 Jan 2015 (estimated)
- Results
- Posted 2 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this crossover, single-dose, bioequivalence study is to compare the rate and extent of absorption of Temozolomide after the administration of the study product (Dralitem®, Monte Verde S.A.) and the reference product (Temodal®, Schering Plough) in primary Central Nervous System patients.
Detailed description
Prospective, randomized, two-period, two treatment, two-way crossover bioequivalence study of two Temozolomide oral formulations (Dralitem vs. Temodal), in primary Central Nervous System tumor patients under fasting conditions. Open label to the patients and investigators and blind to the bioanalytical and clinical laboratories.
Study plan: days -21 to 0 (Recruitment period); days 1 to 5 (Treatment period); days 6 to 21 (Safety surveillance period). Sample size: 24 patients will be randomized. The patients will be administered Temozolomide 200 mg/m2 on the first two days (Dralitem) of the treatment cycle.
They will be admitted to the study clinical site on the evening of day 2. In the morning of day 3 they will be randomized into two groups of equal size. According to the assigned random number, each subject will receive a single oral dose of Temozolomide 200mg/m2 from either Monte Verde Sociedad Anónima (SA) product (Dralitem) or from Schering-Plough product (Temodal). The single dose of 200 mg/m2 will be reached with three different Temozolomide capsule strengths: 20, 100 and 250 mg. Drugs will be administered with 200-240 ml of water in semi-sitting upright position.
The following day (day 4) each subject will receive an oral dose of Temozolomide 200 mg/m2 of the product that did not receive the day before. On days 3 and 4 after drug administration, blood samples will be obtained for pharmacokinetic evaluation. The patient will be discharged from the clinical site on day 4 after completion of sampling for pharmacokinetic analysis. On day 5, all patients will receive Temozolomide 200 mg/m2 (Dralitem).
On days 3 and 4, samples of venous blood will be withdrawn from the forearm vein of each volunteer at the following time points: 0 (pre-dose) and 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 hours post-dose after each period administration. The washout period between the treatment arms was 10 hours, on days 3 and 4. Samples will be processed according to the validated method MANA (Método Analítico) - PLB (Proyecto Laboratorio Bioanalítico) 004 - TEM (Temozolomide) - 01/01. Measurement of plasma concentration of Temozolomide was performed using High Performance Liquid Chromatography (HPLC) followed by detection by tandem mass spectrometry (MS / MS).
The area under the curve (AUC) and the Cmax levels of the drug vs. time will be obtained for each subject. The resulting values of the logarithmic transformation of these parameters will be used for statistical comparisons (mixed effects ANOVA). The limits of the 90% confidence interval for the ratio of log transformed pharmacokinetic parameters will be calculated. Bioequivalence criteria: each calculated confidence interval should be within the acceptance range from 80.00 to 125.00.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Temodal | Active comparator | Drug: TemozolomideTemozolomide (Schering-Plough) 200 mg/m2, single oral dose. |
| Dralitem | Experimental | Drug: TemozolomideTemozolomide (Monte Verde S.A.) 200 mg/m2, single oral dose |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female patients with primary malignant tumors of the central nervous system (CNS) excluding subjects with primary CNS lymphoma.
- Age> 21 years.
- There should be a gap of two weeks between the last surgery and/or radiotherapy procedure and the day of randomization. If the procedure were intrabdominal, the gap should be of four weeks.
- Patients with neutrophils> 1.5 x 109 / L and platelets> 100 x 109 / L.
- Signed written informed consent for participation in the trial.
Key exclusion criteria (10 listed)
- Known hypersensitivity to Temozolomide or any other ingredient of the pharmaceutical formulation.
- Any situation (eg. vomiting) that may interfere with the absorption of the product under study.
- Chemotherapy or biological therapy within four weeks prior to administering the products under study.
- Patients who experience any symptoms of toxicity to prior antineoplastic therapies upon administration of the products under study.
- Participation in other clinical research studies during the 90 days before the start of this study.
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 |
|---|---|---|
| TemozolomideAlso: Temodal | Drug | Temodal |
| TemozolomideAlso: Dralitem | Drug | Dralitem |
Primary outcome
Cmax
Time frame: 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 hours on Days 3 and 4
Rate of absorption of Temozolomide (Cmax) will be measured after the oral administration of the test product (Dralitem®, Monte Verde S.A.) or the reference product (Temodal®, Schering-Plough).
AUC0-t
Time frame: 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 hours on Days 3 and 4
Extent of absorption of Temozolomide from time (0) to the last quantifiable concentration (t) will be measured after the oral administration of the test product (Dralitem®, Monte Verde S.A.) or the reference product (Temodal®, Schering-Plough)
AUC0-∞
Time frame: 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 hours on Days 3 and 4
Extent of absorption of Temozolomide from time (0) to infinity (∞) will be measured after oral administration of the test product (Dralitem®, Monte Verde S.A.) or the reference product (Temodal®, Schering-Plough).
1 secondary outcome
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to two weeks post last dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28756607Muggeri A, Vago M, Perez S, Rubio M, Gonzalez C, Magarinos C, Rosenberg M, Costa F, Perez-Lloret S. A Randomized, Open-Label, Two-Way Crossover, Single-Dose Bioequivalence Study of Temozolomide 200 mg/m2 (Dralitem(R) vs. Temodal(R) Capsules) in Patients with Primary Tumors of the Central Nervous System Under Fasting Conditions. Drugs R D. 2017 Sep;17(3):427-434. doi: 10.1007/s40268-017-0199-3.
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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.
Alejandro D Muggeri, Physician principal investigator
FLENI Instituto Clínico-Quirúrgico de Diagnóstico y Tratamiento
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Temozolomide in people with Brain Neoplasms, Malignant, Primary, run by Monte Verde SA at 2 sites 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 5 inclusion and 10 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 2 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Cmax (time frame: 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 hours on Days 3 and 4). The study lists 3 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 NCT02343081, 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 2 Apr 2015.