Bioequivalence Study of Salbutamol 4 mg Tablet Manufactured by PT. Kimia Farma Tbk Compared to Ventolin® 2x2 mg Tablet Manufactured by PT. Glaxo Wellcome Indonesia
| 1. Background | |
|---|---|
| Registration Number | INA-F69KPE1 |
| Date of registry approval | 09-04-2024 |
| Registration Date | 04-04-2024 |
| Secondary identifiers | Yes |
| Name of issuing authority (for example protocol number, other registries, etc) | |
| Secondary identifier number | |
| Scientific study title | BIOEQUIVALENCE STUDY OF SALBUTAMOL 4 MG TABLET MANUFACTURED BY PT. KIMIA FARMA Tbk COMPARED TO VENTOLIN® 2x2 MG TABLET MANUFACTURED BY PT. GLAXO WELLCOME INDONESIA |
| Public (popular study title) | Bioequivalence Study of Salbutamol 4 mg Tablet Manufactured by PT. Kimia Farma Tbk Compared to Ventolin® 2x2 mg Tablet Manufactured by PT. Glaxo Wellcome Indonesia |
| 2. Sponsor and Funding | |
| Primary Sponsor | PT Kimia Farma Tbk |
| Source(s) of monetary or material support | from the sponsor, PT Kimia Farma Tbk |
| Other partners | EQuitrust Lab - PT Kimia Farma Diagnostika |
| 3. Contact details | |
| Principal Investigator | |
| Principal investigator | Dr. Priyanto, Pharm, B.Pharm, M.Biomed |
| City | Jakarta |
| Country | Indonesia |
| Principal investigator's affiliation | Study Coordinator - Bayu Hadi Wahyono, Pharm, B.Pham, 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 – INDONESIA Phone. +62 821 2559 0521 |
| 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 – 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 | 01/21.06/01080 |
| Name of Ethics committee | Komisi Etik Penelitian Kesehatan Universitas Muhammadiyah Prof. Dr. Hamka (KEPK - HAMKA) |
| Date of Ethic approval | 12-06-2024 |
| Contact details of Ethic Committee (phone, email, and office) | Komisi Etik Penelitian Kesehatan - UHAMKA Jl. Tanah Merdeka, Rambutan, Jakarta Timur email: kepk@uhamka.ac.id telp: 081219053371 |
| Number of Persetujuan Pelaksanaan Uji Klinik (PPUK)/Persetujuan Protokol Uji BE (PPUB) | RG.01.02.321.10.21.00425/UB |
| 5. Status | |
| Countries of recruitment | Indonesia |
| Study sites in Indonesia | EQuitrust Laboratory - PT. Kimia Farma Diagnostika |
| Recruitment status | Complete |
| Date of first enrollment | 22-10-2021 |
| Targeted Sample size | 00024 - |
| Number of enrolled participants | 24 |
| Date of study completion (last participant, last visit) | 01-11-2021 |
| 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 | The aim of this study was to determine the bioequivalence of Salbutamol 4 mg Tablet Manufactured by PT. Kimia Farma Tbk Compared to Ventolin® 2x2 mg Tablet Manufactured by PT. Glaxo Wellcome Indonesia |
| 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) | Salbutamol 4 mg Tablet Manufactured by PT. Kimia Farma Tbk |
| Control intervention (control arm) | Ventolin® 2x2 mg Tablet Manufactured by PT. Glaxo Wellcome 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 | 1) Smoking more than 10 cigarettes per day;
2) Pregnant or breastfeeding women. Pregnancy tests will be 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 (Salbutamol); 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 14 times at the following time points: 0 hours (before drug administration), at 0.20, 0.40, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours after drug administration (14 points) |
| 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 14 times at the following time points: 0 hours (before drug administration), at 0.20, 0.40, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours after drug administration (14 points) |
| 9. Study Results | |
| Brief summary of study results | The present study demonstrated that the evaluated test drug Salbutamol (BN:
A00035N) were bioequivalence interm of both rate and extent of absorption to the reference drug Ventolin (BN: 424T). |
| Date of results summaries | 29-12-2021 |
| Participant flow | Recruitment of subjects and recruitment information has 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 will be provided with detailed explanations in easily understandable language, including the risks and benefits of this study. Prospective subjects who meet the inclusion and exclusion criteria will be recruited as subjects after signing informed consent. They will be 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 undergo a rapid SARS-CoV-2 antigen test) |
| Baseline characteristic | |
| Adverse events | Some subjects reported adverse events during this bioequivalence study, which were chest pounding. All of these adverse events were recorded in the CRF |
| Outcome measures | The point estimates and 90%
confidence intervals (CI) for AUC0-24h were 96,35% (90,55-102,53) and Cmax were 105,39% (93,62-118,65) |
| 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 | |