BIOEQUIVALENCE STUDY OF AMLODIPINE 10 MG TABLET PRODUCED BY PT MAHAKAM BETA FARMA IN COMPARISON WITH NORVASK® (AMLODIPINE 10 MG) TABLET MANUFACTURED BY PT PFIZER INDONESIA.
| 1. Background | |
|---|---|
| Registration Number | INA-G1SOG60 |
| Date of registry approval | 17-01-2024 |
| Registration Date | 04-01-2024 |
| Secondary identifiers | Yes |
| Name of issuing authority (for example protocol number, other registries, etc) | PT. Omega Medika Farma Laboratori |
| Secondary identifier number | No. 174/FORM/OMF/2023 versi 01 |
| Scientific study title | BIOEQUIVALENCE STUDY OF AMLODIPINE 10 MG TABLET PRODUCED BY PT MAHAKAM BETA FARMA IN COMPARISON WITH NORVASK® (AMLODIPINE 10 MG) TABLET MANUFACTURED BY PT PFIZER INDONESIA. |
| Public (popular study title) | BIOEQUIVALENCE STUDY OF AMLODIPINE 10 MG TABLET PRODUCED BY PT MAHAKAM BETA FARMA IN COMPARISON WITH NORVASK® (AMLODIPINE 10 MG) TABLET MANUFACTURED BY PT PFIZER INDONESIA. |
| 2. Sponsor and Funding | |
| Primary Sponsor | PT. Mahakam Beta Farma |
| Source(s) of monetary or material support | - |
| Other partners | - |
| 3. Contact details | |
| Principal Investigator | |
| Principal investigator | apt. Noviyanto, S.Farm. |
| City | Jakarta |
| Country | Indonesia |
| Principal investigator's affiliation | PT. Omega Medika Farma Laboratori |
| Principal Investigator's email address | noviyanto@omegaresearch.id |
| Public Queries | |
| Contact person name for public queries | apt. Noviyanto, S.Farm. |
| Address for public queries | Jalan Kramat Raya No. 61A Jakarta, 10450 Indonesia Phone: +62 21 3905831; +62 21 3905813 |
| City | Jakarta |
| Country | Indonesia |
| ZIP | 10450 |
| Affiliation for public queries | PT. Omega Medika Farma Laboratori |
| Email address for public queries | quality@omegaresearch.id, klinis@omegaresearch.id |
| Phone number for public queries | +62 21 3905831, +62 21 3905813 |
| Scientific Queries | |
| Name of Contact for scientific queries | apt. Tasha Yuliandra, M.Sc. |
| Address for scientific queries | Jalan Kramat Raya No. 61A Jakarta, 10450 Indonesia Phone: +62 21 3905831; +62 21 3905813 |
| City | Jakarta |
| Country | Indonesia |
| ZIP | 10450 |
| Affiliation of scientific queries contact | PT. Omega Medika Farma Laboratori |
| Email address for scientific queries | quality@omegaresearch.id, klinis@omegaresearch.id |
| 4. IRB & Regulatory | |
| Ethical Approval number | KET-649/UN2.F1/ETIK/PPM.00.02/2023 |
| Name of Ethics committee | KOMITE ETIK PENELITIAN KESEHATAN RSUP NASIONAL DR. CIPTO MANGUNKUSUMO FAKULTAS KEDOKTERAN UNIVERSITAS INDONESIA |
| Date of Ethic approval | 29-05-2023 |
| Contact details of Ethic Committee (phone, email, and office) | Gedung H Fakultas Kedokteran UI, Jalan Salemba Raya No. 6 Jakarta 10430 PO. Box 1358 Telp: (021) 3157008, website: https://komite-etik.fk.ui.ac.id |
| Number of Persetujuan Pelaksanaan Uji Klinik (PPUK)/Persetujuan Protokol Uji BE (PPUB) | RG.01.02.321.06.23.01849/UB |
| 5. Status | |
| Countries of recruitment | Indonesia |
| Study sites in Indonesia | PT Omega Medika Farma Laboratori |
| Recruitment status | Complete |
| Date of first enrollment | 12-08-2023 |
| Targeted Sample size | 00018 - |
| Number of enrolled participants | 17 |
| Date of study completion (last participant, last visit) | 13-09-2023 |
| 6. Study Design & Purpose | |
| Primary health condition(s) or problem(s) studied (e.g., depression, breast cancer,medication error) | in male healthy subjects with two weeks washout period |
| Purpose of the study | to assess the bioequivalence |
| Study type | Interventional |
| Interventional Study category | Bioequivalence study |
| Method of allocation | |
| Description of the allocation concealment mechanism and sequence generation | |
| Masking | |
| Study intervention (study arm) | Bioequivalence study of Amlodipine 10 mg tablet produced by PT Mahakam Beta Farma in comparison with Norvask® (Amlodipine 10 mg) tablet manufactured by PT Pfizer Indonesia. |
| Control intervention (control arm) | The design was a single dose, randomized, single-blind, two periods, crossover study, fasting condition, in male healthy subjects with two weeks washout period. |
| Intervention assignment | Crossover |
| 7. Eligibility Criteria | |
| Gender inclusion criteria | Male |
| Minimum age | 18 |
| Maximum age | 55 |
| Inclusion criteria | - Willing to sign the informed consent,
- Age 18 – 55 years, - Body mass index between 18 – 25 kg/m2, - Normotensive (systolic blood pressure 100 – 120 mmHg, diastolic blood pressure 60- 80 mmHg), heart rate 60 – 90 beats per minute, - Healthy male (healthy criteria is determined by normal values or if outside the normal range of values but no clinically significant effects based on doctors' justification on the result of laboratory test include routine hematology, liver function, renal function, blood sugar and urinalysis; history of disease, and physical examination), |
| Exclusion criteria | - Contraindicated and/or has history of hypersensitivity to Amlodipin or related calcium
channel blocker (nifedipine, diltiazem HCl, verapamil, or felodipine) - With history or present medical condition which might significantly influence the pharmacokinetics of the study drug, e.g. chronic gastrointestinal disease, diarrhea, gastric surgery, renal insufficiency, hepatic dysfunction or cardiovascular disease, - Presence of any clinically significant abnormal values during screening e.g. significant abnormality of liver function test (ASL, 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. - Clinically significant hematology abnormalities. - Clinically significant in the electrocardiography (ECG) test result. - Using any medication (prescription or non-prescription drug, food supplement, herbal medicine) within 14 days prior to the dosing day, - Participated in any clinical study within 3 months prior the study, - Donated or lost 300 mL (or more) of blood within 3 months prior the study, - Smoke more than 9 sticks of cigarettes a day, |
| 8. Study Outcome | |
| Primary Outcome | |
| Name of primary outcome | From the result of study, it was concluded that Amlodipine 10 mg tablet batch number CS23010 produced by PT Mahakam Beta Farma was bioequivalent to its reference Norvask® (Amlodipine 10 mg) tablet batch number FX9585 manufactured by PT Pfizer Indonesia. |
| Metric/method of measurement | Sample collection Blood samples for Amlodipine analysis were withdrawn into collecting tubes (containing citrate phosphate dextrose adenine solution as anticoagulant). Five mL of each blood sample was collected by vein puncture at the forearm of each subject. Seventeen samples were drawn at 0 (before dosing), at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours after dosing. The blood samples were centrifuged (3500 RPM; 18.5 cm rotor diameter; 10 min; 4oC) and the plasma fractions were separated and kept at -20 ± 5ºC until analysis. Sample analysis Plasma containing Amlodipine was measured by a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Validation was done by analyte spike into plasma that has been separated with citrate phosphate dextrose adenine solution. The mass spectrometer was operated using an electrospray atmospheric pressure ionization source in positive ion mode (ESI+) with Multiple Reaction Monitoring (MRM). The lower limit of quantitation for Amlodipine is 0.1 ng/mL and Gliclazide was used as internal standard. There was no reanalysis of sample in this study. Statistical Procedure Bioequivalence of the drug formulations (Test vs Reference) were assessed by comparing the AUC0→t’ and Cmax values after ln transformation of the data. The geometric mean ratio (test/reference) and 90% confidence intervals, was analyzed with a parametric method (analysis of variance/ANOVA) using EquivTest PK (Statistical Solution Ltd, Saugus. MA, USA). T1/2 and Tmax were analyzed with nonparametric method using Wilcoxon test. |
| Timepoint(s) of measurement | Sample collection Blood samples for Amlodipine analysis were withdrawn into collecting tubes (containing citrate phosphate dextrose adenine solution as anticoagulant). Five mL of each blood sample was collected by vein puncture at the forearm of each subject. Seventeen samples were drawn at 0 (before dosing), at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours after dosing. The blood samples were centrifuged (3500 RPM; 18.5 cm rotor diameter; 10 min; 4oC) and the plasma fractions were separated and kept at -20 ± 5ºC until analysis. |
| 9. Study Results | |
| Brief summary of study results | From the result of study, it was concluded that Amlodipine 10 mg tablet batch number CS23010
produced by PT Mahakam Beta Farma was bioequivalent to its reference Norvask® (Amlodipine 10 mg) tablet batch number FX9585 manufactured by PT Pfizer Indonesia. |
| Date of results summaries | 04-10-2023 |
| 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 | |