Bioequivalence study of trimetazidine dihydrochloride 35 mg modified release tablet produced by PT Dexa Medica for PT Ferron Par Pharmaceuticals in comparison with the comparator drug (Vastarel® 35 mg Modified Release Tablet, Les Laboratoires Servier Industrie, France) when administered under fasting condition in healthy subjects.
| 1. Background | |
|---|---|
| Registration Number | INA-F3TTW81 |
| Date of registry approval | 09-04-2024 |
| Registration Date | 03-04-2024 |
| Secondary identifiers | No |
| Name of issuing authority (for example protocol number, other registries, etc) | |
| Secondary identifier number | |
| Scientific study title | Bioequivalence study of trimetazidine dihydrochloride 35 mg modified release tablet produced by PT Dexa Medica for PT Ferron Par Pharmaceuticals in comparison with the comparator drug (Vastarel® 35 mg Modified Release Tablet, Les Laboratoires Servier Industrie, France) when administered under fasting condition in healthy subjects. |
| Public (popular study title) | Bioequivalence study of trimetazidine dihydrochloride 35 mg modified release tablet produced by PT Dexa Medica for PT Ferron Par Pharmaceuticals in comparison with the comparator drug (Vastarel® 35 mg Modified Release Tablet, Les Laboratoires Servier Industrie, France) when administered under fasting condition in healthy subjects. |
| 2. Sponsor and Funding | |
| Primary Sponsor | PT Ferron Par Pharmaceuticals |
| Source(s) of monetary or material support | PT Ferron Par Pharmaceuticals |
| Other partners | PT Equilab International |
| 3. Contact details | |
| Principal Investigator | |
| Principal investigator | Danang Agung Yunaidi, MD |
| City | Jakarta |
| Country | Indonesia |
| Principal investigator's affiliation | Natalia Denda Wijaya, MD |
| Principal Investigator's email address | natalia.wijaya@equilab-int.com |
| Public Queries | |
| Contact person name for public queries | Kartika Widyanty |
| Address for public queries | Jl. Boulevard Bintaro Blok B7/B1 No. 05 Bintaro Jaya Sektor 7 Tangerang Selatan 15224 – INDONESIA. |
| City | Tangerang Selatan |
| Country | Indonesia |
| ZIP | 15224 |
| Affiliation for public queries | Monica Mutiara Anindita |
| Email address for public queries | monica.anindita@dexa-medica.com |
| Phone number for public queries | 085290819937 |
| Scientific Queries | |
| Name of Contact for scientific queries | Kartika Widyanty |
| Address for scientific queries | Jl. Boulevard Bintaro Blok B7/B1 No. 05 Bintaro Jaya Sektor 7 Tangerang Selatan 15224 – INDONESIA. |
| City | Tangerang Selatan |
| Country | Indonesia |
| ZIP | 15224 |
| Affiliation of scientific queries contact | Kartika Widyanty |
| Email address for scientific queries | kartika.widyanty@dexa-medica.com |
| 4. IRB & Regulatory | |
| Ethical Approval number | KET-1079/UN2.F1/ETIK/PPM.00.02/2023 |
| Name of Ethics committee | The Ethics Committee of Faculty of Medicine, University of Indonesia – Cipto Mangunkusumo Hospital. |
| Date of Ethic approval | 21-08-2023 |
| Contact details of Ethic Committee (phone, email, and office) | Gedung Fakultas Kedokteran UI Jalan Salemba Raya No.6, Jakarta Phone : 0213912477 Email : humas@fk.ui.ac.id |
| Number of Persetujuan Pelaksanaan Uji Klinik (PPUK)/Persetujuan Protokol Uji BE (PPUB) | RG.01.02.321.09.23.02040/UB |
| 5. Status | |
| Countries of recruitment | Indonesia |
| Study sites in Indonesia | PT Equilab International - Fatmawati, Jakarta. |
| Recruitment status | Complete |
| Date of first enrollment | 27-09-2023 |
| Targeted Sample size | 00024 - |
| Number of enrolled participants | 24 |
| Date of study completion (last participant, last visit) | 05-10-2023 |
| 6. Study Design & Purpose | |
| Primary health condition(s) or problem(s) studied (e.g., depression, breast cancer,medication error) | Healthy male and female subjects with absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening and could be considered healthy based on the evaluation. |
| Purpose of the study | Bioequivalence study |
| Study type | Observational |
| Method of allocation | |
| Description of the allocation concealment mechanism and sequence generation | |
| Masking | |
| Study intervention (study arm) | |
| Control intervention (control arm) | |
| Intervention assignment | |
| 7. Eligibility Criteria | |
| Gender inclusion criteria | Male, Female |
| Minimum age | 18 years |
| Maximum age | 55 years |
| Inclusion criteria | 1. Able to participate, communicate well with the investigators and willing to provide written
informed consent to participate in the study. 2. Healthy male and female subjects with absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during the screening and could be considered healthy based on the evaluation. 3. Aged 18 - 55 years inclusive. 4. Non-smokers. 5. Body mass index within 18 to 25 kg/m2. 6. Vital signs (after 10 minutes rest) must be within the following ranges. - Systolic blood pressure : 110 - 129 mmHg - Diastolic blood pressure : 70 - 84 mmHg - Pulse rate : 60 - 90 bpm 7. Willing to practice abstention or use non-hormonal contraception during the study. |
| Exclusion criteria | 1. History of allergy or hypersensitivity or contraindication to trimetazidine or allied drugs.
2. Pregnant or lactating female (urinary pregnancy test was applied to female subjects at screening and before taking the study drug). 3. Any major illness in the past 90 days or clinically significant ongoing chronic medical illness. 4. Presence of any clinically significant abnormal values during screening e.g. significant abnormality of liver function test (AST, ALT, alkaline phosphatase, total bilirubin, direct bilirubin ≥ 1.5 ULN), renal function test (serum creatinine concentration > 1.4 mg/dL and ureum ≥ 1.5 ULN), etc. 5. Positive Hepatitis B surface antigen (HBsAg), anti-HCV, or anti-HIV. 6. Clinically significant hematology abnormalities. 7. Clinically significant electrocardiogram (ECG) abnormalities. 8. Any surgical or medical condition (present or history) which might significantly alter the absorption, distribution, metabolism or excretion of the study drug, e.g. gastrointestinal disease including gastric or duodenal ulcers or history of gastric surgery. 9. Past history of anaphylaxis or angioedema. 10. History of drug or alcohol abuse within 12 months prior to screening for this study. 11. Participation in any clinical trial within the past 90 days calculated from the last visit until this study’s first dosing day. 12. History of any bleeding or coagulative disorders. 13. Presence of difficulty in accessibility of veins in left or right arm. 14. A donation or significant blood loss within 90 days before this study’s first dosing day. 15. Intake of any prescription drug (especially trimetazidine and antihypertensive drug), non-prescription drug (including hormonal contraception), food supplements or herbal medicines within 21 days of this study’s first dosing day. 16. History of parkinson disease, parkinsonian symptoms, tremors, restless leg syndrome and other related movement disorders. 17. Having creatinine clearance (CrCl) ≤60 mL/min at screening. |
| 8. Study Outcome | |
| Primary Outcome | |
| Name of primary outcome | To find out whether the bioavailability of trimetazidine dihydrochloride 35 mg modified release tablet produced by PT Dexa Medica for PT Ferron Par Pharmaceuticals was equivalent to the comparator drug (Vastarel® 35 mg Modified Release Tablet, Les Laboratoires Servier Industrie, France) when administered under fasting condition in healthy subjects. |
| Metric/method of measurement | The bioequivalence of the products was concluded based on the 90% confidence intervals of the test/comparator geometric mean ratios of Trimetazidine’s AUC0-t and Cmax which were within the range of 80.00 - 125.00%. |
| Timepoint(s) of measurement | The subjects blood samples will be taken at a certain time. Drug administration, drink and meal for subjects, and subject activities will be standardized during study period. |
| 9. Study Results | |
| Brief summary of study results | It was concluded that the trimetazidine dihydrochloride 35 mg modified release tablet produced by PT Dexa Medica for PT Ferron Par Pharmaceuticals was bioequivalent to the comparator drug (Vastarel® 35 mg Modified Release Tablet, Les Laboratoires Servier Industrie, France) in healthy subjects, |
| Date of results summaries | |
| Participant flow | |
| Baseline characteristic | |
| Adverse events | |
| Outcome measures | |
| 10. Publication | |
| URL hyperlink(s) related to results and publications | |
| IPD sharing statement (Statement regarding the intended sharing of deidentified individual clinical trial participant-level data (IPD)) | |
| Plan for IPD sharing (what IPD will be shared, when, by what mechanism, with whom, and for what types of analyses) | |
| Other important informations | |