Bioequivalence Study of Amlodipine 10 mg Tablet Manufactured by PT. Tropica Mas Pharmaceuticals Compared to Norvask 10 mg Tablet Manufactured by PT. Pfizer Indonesia
| 1. Background | |
|---|---|
| Registration Number | INA-0YSGS0S |
| Date of registry approval | 27-03-2024 |
| Registration Date | 22-03-2024 |
| Secondary identifiers | Yes |
| Name of issuing authority (for example protocol number, other registries, etc) | |
| Secondary identifier number | |
| Scientific study title | BIOEQUIVALENCE STUDY OF AMLODIPINE 10 MG TABLET MANUFACTURED BY PT. TROPICA MAS PHARMACEUTICALS COMPARED TO NORVASK 10 MG TABLET MANUFACTURED BY PT. PFIZER INDONESIA |
| Public (popular study title) | Bioequivalence Study of Amlodipine 10 mg Tablet Manufactured by PT. Tropica Mas Pharmaceuticals Compared to Norvask 10 mg Tablet Manufactured by PT. Pfizer Indonesia |
| 2. Sponsor and Funding | |
| Primary Sponsor | PT. Tropica Mas Pharmaceuticals |
| Source(s) of monetary or material support | from the Sponsor, PT. Tropica Mas Pharmaceuticals |
| Other partners | EQuitrust Laboratory - PT. Kimia Farma Diagnostika |
| 3. Contact details | |
| Principal Investigator | |
| Principal investigator | Dr. Priyanto, Pharm, M.Biomed |
| City | Jakarta |
| Country | Indonesia |
| Principal investigator's affiliation | Study Coordinator - Bayu Hadi Wahyono, Pharm, B.Pharm, MPH |
| Principal Investigator's email address | Priyanto@equitrstlab.com |
| Public Queries | |
| Contact person name for public queries | Bayu Hadi Wahyono, Pharm, B.Pham, MPH - Study Coordinator (085773150080 - lab.equitrust@gmail.com) |
| Address for public queries | PT. Kimia Farma Diagnostika EQuitrust Laboratory Jl. Bendungan Hilir Raya No. 60 Central Jakarta 10210 – INDONESIA |
| City | Jakarta |
| Country | Indonesia |
| ZIP | 10210 |
| Affiliation for public queries | https://www.equitrustlab.com/ |
| Email address for public queries | lab.equitrust@gmail.com |
| Phone number for public queries | +62 821 2559 0521 & 085773150080 |
| Scientific Queries | |
| Name of Contact for scientific queries | Dr. Priyanto, Pharm, B.Pharm, M.Biomed |
| Address for scientific queries | PT. Kimia Farma Diagnostika EQuitrust Laboratory Jl. Bendungan Hilir Raya No. 60 Central Jakarta 10210 – INDONESIA |
| City | Jakarta |
| Country | Indonesia |
| ZIP | 10210 |
| Affiliation of scientific queries contact | Study coordinator - Bayu Hadi Wahyono |
| Email address for scientific queries | lab.equitrust@gmail.com |
| 4. IRB & Regulatory | |
| Ethical Approval number | KET-1304/UN2.F1/ETIK/PPM.00.02/2023 |
| Name of Ethics committee | Komite Etik Penelitian Kesehatan, Fk Universitas Indonesia - Rsupn Dr. Cipto Mangunkusumo |
| Date of Ethic approval | 06-10-2023 |
| Contact details of Ethic Committee (phone, email, and office) | Komite Etik FKUI/RSCMJl. Salemba 6, Jakarta Pusat Telp. 021 315 7008e-Mail: ec_fkui@yahoo.com |
| Number of Persetujuan Pelaksanaan Uji Klinik (PPUK)/Persetujuan Protokol Uji BE (PPUB) | RG.01.02.321.11.23.02279/UB |
| 5. Status | |
| Countries of recruitment | Indonesia |
| Study sites in Indonesia | EQuitrust Laboratory - PT. Kimia Farma Diagnostika |
| Recruitment status | Complete |
| Date of first enrollment | 14-12-2023 |
| Targeted Sample size | 00018 - |
| Number of enrolled participants | 18 |
| Date of study completion (last participant, last visit) | 05-01-2024 |
| 6. Study Design & Purpose | |
| Primary health condition(s) or problem(s) studied (e.g., depression, breast cancer,medication error) | this study was conducted on healthy human subjects |
| Purpose of the study | This study aims to determine the bioequivalence of Amlodipine 10 mg Tablet Manufactured by PT. Tropica Mas Pharmaceuticals Compared to Norvask 10 mg Tablet Manufactured PT. Pfizer Indonesia, in healthy subjects. |
| 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) | Amlodipine 10 mg Tablet Manufactured by PT. Tropica Mas Pharmaceuticals |
| Control intervention (control arm) | Norvask 10 mg Tablet Manufactured by PT. Pfizer Indonesia |
| Intervention assignment | Crossover |
| 7. Eligibility Criteria | |
| Gender inclusion criteria | Male, Female |
| Minimum age | 18 |
| Maximum age | 55 |
| Inclusion criteria | The inclusion criteria for this study include:
1) Signed informed consent; 2) Healthy based on clinical laboratory tests (routine hematology, liver function, kidney function, blood glucose, urinalysis, hepatitis B (HBsAg), hepatitis C (Anti-HCV), and HIV (Anti-HIV), medical history, and physical examination); 3) Male and female subjects (if female, consider the risks for women of childbearing age and perform pregnancy tests); 4) Age between 18-55 years; 5) Normal weight range according to Body Mass Index (BMI) 18-25 kg/m2); 6) Vital signs within the following ranges: systolic blood pressure 110-129 mmHg, diastolic blood pressure 70-84 mmHg, normal pulse rate 60-90 bpm, oxygen saturation (SpO2) in the normal range of 95-100%, and normal respiratory rate of 12-20/min. |
| Exclusion criteria | The exclusion criteria for this study include:
1) Smoking more than 10 cigarettes per day; 2) Pregnant or breastfeeding women. Pregnancy tests was performed during screening and prior to the administration of the investigational or comparator drug; 3) History of kidney or liver disease, or history of allergy, hypersensitivity or contraindication to the investigational bioequivalence drug (Amlodipine); 4) Clinically significant hematological abnormalities; 5) Abnormal electrocardiogram (ECG); 6) Difficulty accessing veins in the left or right arm; 7) History of significant ongoing clinically or medically significant chronic or acute illness; 8) History of drug or alcohol abuse within the past 12 months (1 year) prior to screening for this study; 9) Positive serology test results for Hepatitis B (HBsAg), Hepatitis C (anti-HCV), HIV (anti-HIV). 10) Positive rapid antigen test results for SARS-CoV-2 (if the BE study is conducted during a pandemic). 11) History or condition that can affect drug kinetics. 12) Use of drugs or dietary supplements no more than 7 days since the start of the study. 13) Participation in previous clinical trials no more than 3 months from the start of the study. 14) Blood donation or blood loss of more than 300 ml within 3 months from the start of the study. |
| 8. Study Outcome | |
| Primary Outcome | |
| Name of primary outcome | AUC0-t , Cmax |
| Metric/method of measurement | Bioequivalence between the test and reference products was determined based on the average ratios of Cmax and AUC0-t with a 90% Confidence Interval (90% CI) of the log or ln-transformed data. The log or ln-transformed values of Cmax and AUC0-t for the two products are analyzed using a two-way Analysis of Variance (ANOVA) and R program. The compared factors were the drug products (Test and Reference), drug administration period (I and II), subject, and sequence (TR and RT). The mean differences in Cmax and AUC0-t between the test and reference products were considered bioequivalent if the ratio of the geometric mean (AUC)T/(AUC)R= 1.00 with 90% CI= 80.00-125.00% (α: 0.05) and (Cmax)T/(Cmax)R= 1.00 with 90% CI= 80.00-125.00% (α: 0.05). The study had a power of 80% with a significance level (alpha) of 5% (two-tailed). |
| Timepoint(s) of measurement | Blood samples were collected 17 times at the following time points: 0 hours (prior to drug administration); hour 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 36, 48, 72 hours after drug administration |
| Secondary outcome 1 | |
| Name of secondary outcome 1 (SO1) | AUC0-inf , Tmax, Half life |
| Metric/method of measurement (SO1) | Pharmacokinetic parameters, including Cmax, AUC0-t, AUC0-inf, tmax, and t1/2, were calculated for each subject and each period using the Ms. Excel program |
| Timepoint(s) of measurement (SO1) | Blood samples were collected 17 times at the following time points: 0 hours (prior to drug administration); hour 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 36, 48, 72 hours after drug administration |
| 9. Study Results | |
| Brief summary of study results | The present study demonstrated that the evaluated test drug Amlodipine (BN: PF017R) were
bioequivalence interm of both rate and extent of absorption to the reference drug Norvask (BN: GG7322) |
| Date of results summaries | 24-01-2024 |
| Participant flow | Recruitment of subjects and recruitment information have been done through advertisements/broadcast messages on social media or research posters. Subjects must participate voluntarily, and they are free to withdraw from the study at any time. They have been given detailed explanations in easily understandable language, including the risks and benefits of this study.
Prospective subjects who meet the inclusion and exclusion criteria have been recruited as subjects after signing informed consent. They have been given a copy of the signed consent form. After that, the subjects will undergo physical examination by a doctor, and clinical laboratory tests will include routine hematology, liver function, kidney function, blood glucose, urinalysis, hepatitis B (HBsAg), hepatitis C (Anti-HCV), HIV (Anti-HIV), and ECG (before the screening process begins, prospective subjects and research personnel will undergo rapid antigen test for SARS-CoV-2). Verification of the signed consent is recorded in the Case Report Form (CRF) of the study. As a preventive measure against SARS-CoV-2 transmission, the research site will undergo routine disinfection spraying both before and after the study. After signing the consent form following the explanation/informed consent, the subjects will undergo SARS-CoV-2 testing using a rapid antigen test method (antigen swab). Confirmation of SARS-CoV-2 will also be conducted a maximum of H-1 before the implementation of bioequivalence test period 1 and period 2 (quarantine). If the result shows a positive result, the subject will be directed to undergo self-isolation according to the applicable government regulations. Subjects are required to follow health protocols such as wearing masks, washing hands with soap or hand sanitizer, and maintaining social distancing. In addition to subjects, the personnel involved in the bioequivalence test will also undergo SARS-CoV-2 testing and are required to wear hazmat suits, face shields/masks, and gloves during the implementation of the bioequivalence test research. |
| Baseline characteristic | |
| Adverse events | There were adverse events during this bioequivalence study, which were heart
palpitations, headache, nausea, and diarrhea. All of these adverse events were recorded in the CRF |
| Outcome measures | The point estimates and 90% confidence intervals (CI) for AUC0-72h were 101.67% (97.16 – 106.39) with CV Intra Subjects was 7.54% and Cmax were 100.46% (95.00 – 106.23) with CV Intra Subjects was
9.30%. |
| 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)) | No |
| Plan for IPD sharing (what IPD will be shared, when, by what mechanism, with whom, and for what types of analyses) | |
| Other important informations | |