Bioequivalence Study of 80 mg Acetylsalicylic Acid Enteric Coated Tablet, Manufactured by PT Pharos Indonesia (Ascardia®) in Comparison with the Innovator’s 100 mg Acetylsalicylic Acid Enteric Coated Tablet (Cardio Aspirin®), Manufactured by Bayer AG, Leverkusen-Germany for Bayer Consumer Care AG, Switzerland, Imported by PT Bayer Indonesia, Depok-Indonesia
| 1. Background | |
|---|---|
| Registration Number | INA-X2O2802 |
| Date of registry approval | 23-02-2024 |
| Registration Date | 13-02-2024 |
| Secondary identifiers | Yes |
| Name of issuing authority (for example protocol number, other registries, etc) | Econolab |
| Secondary identifier number | PRO-269/23/ECL |
| Scientific study title | Bioequivalence Study of 80 mg Acetylsalicylic Acid Enteric Coated Tablet, Manufactured by PT Pharos Indonesia (Ascardia®) in Comparison with the Innovator’s 100 mg Acetylsalicylic Acid Enteric Coated Tablet (Cardio Aspirin®), Manufactured by Bayer AG, Leverkusen-Germany for Bayer Consumer Care AG, Switzerland, Imported by PT Bayer Indonesia, Depok-Indonesia |
| Public (popular study title) | Bioequivalence Study of 80 mg Acetylsalicylic Acid Enteric Coated Tablet, Manufactured by PT Pharos Indonesia (Ascardia®) in Comparison with the Innovator’s 100 mg Acetylsalicylic Acid Enteric Coated Tablet (Cardio Aspirin®), Manufactured by Bayer AG, Leverkusen-Germany for Bayer Consumer Care AG, Switzerland, Imported by PT Bayer Indonesia, Depok-Indonesia |
| 2. Sponsor and Funding | |
| Primary Sponsor | PT Pharos Indonesia |
| Source(s) of monetary or material support | PT Pharos Indonesia |
| Other partners | Econolab |
| 3. Contact details | |
| Principal Investigator | |
| Principal investigator | dr. Agus Limarta, S.E. |
| City | Jakarta Selatan |
| Country | Indonesia |
| Principal investigator's affiliation | Econolab |
| Principal Investigator's email address | babe@econolab.co.id |
| Public Queries | |
| Contact person name for public queries | Ni Made Dwi Wulandari |
| Address for public queries | Jl. Limo No. 6/45, RT 014 RW 002 Grogol Utara Kebayoran Lama |
| City | Jakarta Selatan |
| Country | Indonesia |
| ZIP | 12210 |
| Affiliation for public queries | Econolab |
| Email address for public queries | babe@econolab.co.id |
| Phone number for public queries | +622127097150 |
| Scientific Queries | |
| Name of Contact for scientific queries | Ni Made Dwi Wulandari |
| Address for scientific queries | Jl. Limo No. 6/45, RT 014 RW 002 Grogol Utara Kebayoran Lama |
| City | Jakarta Selatan |
| Country | Indonesia |
| ZIP | 12210 |
| Affiliation of scientific queries contact | Econolab |
| Email address for scientific queries | babe@econolab.co.id |
| 4. IRB & Regulatory | |
| Ethical Approval number | KET-1464/UN2.F1/ETIK/PPM.00.02/2023 |
| Name of Ethics committee | The Ethics Committee of the Faculty of Medicine, University of Indonesia - Cipto Mangunkusumo Hospital |
| Date of Ethic approval | 23-10-2023 |
| Contact details of Ethic Committee (phone, email, and office) | Phone: 021 3157008 Email: komite-etik@fk.ui.ac.id Office: Gedung H Fakultas Kedokteran UI, Jalan Salemba Raya No. 6, Jakarta 10430 |
| Number of Persetujuan Pelaksanaan Uji Klinik (PPUK)/Persetujuan Protokol Uji BE (PPUB) | RG.01.02.321.12.23.02320/UB |
| 5. Status | |
| Countries of recruitment | Indonesia |
| Study sites in Indonesia | Sentra Uji BE Econolab: Jl. Limo No. 6/45 RT 014 RW 002, Grogol Utara, Kebayoran Lama, Jakarta Selatan 12210. |
| Recruitment status | Complete |
| Date of first enrollment | 02-01-2024 |
| Targeted Sample size | 00034 - |
| Number of enrolled participants | 34 |
| Date of study completion (last participant, last visit) | 11-01-2024 |
| 6. Study Design & Purpose | |
| Primary health condition(s) or problem(s) studied (e.g., depression, breast cancer,medication error) | Thrombosis |
| Purpose of the study | Other |
| 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) | Single dose, 5 tablets of 80 mg Acetylsalicylic Acid enteric coated tablet (Ascardia®), Manufactured by PT Pharos Indonesia |
| Control intervention (control arm) | Single dose, 4 tablets of 100 mg Acetylsalicylic Acid enteric coated tablet (Cardio Aspirin®), Manufactured by Bayer AG, Leverkusen, Germany |
| Intervention assignment | Crossover |
| 7. Eligibility Criteria | |
| Gender inclusion criteria | Male, Female |
| Minimum age | 18 |
| Maximum age | 55 |
| Inclusion criteria | Able to participate, communicate well with the investigators and agree to sign an informed consent; Willing to use contraception (condoms) when intercourse with spouse during the study; Healthy male/female subjects as determined by the medical screening assessments, do not show any symptoms of Covid-19; Aged 18-55 years; Body mass index (BMI) is in the range of 18-25 kg/m²; Have received the complete primary SARS-CoV-2 vaccine and at least the first booster; Normal blood pressure (systolic 100-120 mmHg; diastolic 60-80 mmHg); Normal pulse rate (60-90 bpm); Normal electrocardiogram (ECG); Clinical laboratory results must be within normal range (medical judgement of responsible physician determined any laboratory finding beyond its standard value) |
| Exclusion criteria | Pregnant or lactating women (urinary pregnancy test to be applied to female subjects when screening and just before taking the test or reference drug); Known hypersensitivity or contraindication to Acetylsalicylic Acid, Ibuprofen, or other NSAIDs; Intake of any prescription drug or non-prescription drug/food supplement/herbal medicine within seven (7) days of this study’s first dosing day; History of any bleeding, including non-trauma-related hemorrhage, or coagulation disorders; Any surgical or medical condition (present or history) which might significantly alters the absorption, distribution, metabolism or excretion of the study drug, e.g. gastrointestinal diseases including gastric or duodenal ulcers or history of gastric surgery; Frequent indigestion, or heartburn; History of stroke, myocardial infarction, or congestive heart failure; History of asthma, other bronchospastic activity, nasal polyps, or angioedema; History of thrombocytopenia, neutropenia, kidney or liver disease, or chronic hypertension; A donation or loss of 300 mL (or more) of blood within three (3) months before this study’s first dosing day; A positive Hepatitis B surface antigen (HBsAg), HCV, HIV test result; History of drug or alcohol abuse within twelve (12) months prior to the study; Heavy smoker (more than 10 cigarettes a day); Had clinically significant bleeding within three (3) months prior to the study; Participation in a previous study within three (3) months of this study’s first dosing day |
| 8. Study Outcome | |
| Primary Outcome | |
| Name of primary outcome | AUC0-t and Cmax |
| Metric/method of measurement | Determination of Salicylic Acid concentration in biological sample (plasma) using UPLC-MS/MS |
| Timepoint(s) of measurement | 0, ½, 1, 1½, 2, 2½, 3, 3½, 4, 4½, 5, 6, 8, 10, 12, 16, 24, and 36 hours post dosing |
| Secondary outcome 1 | |
| Name of secondary outcome 1 (SO1) | AUC0-t, Tmax, T1/2 |
| Metric/method of measurement (SO1) | Determination of Salicylic Acid concentration in biological sample (plasma) using UPLC-MS/MS |
| Timepoint(s) of measurement (SO1) | 0, ½, 1, 1½, 2, 2½, 3, 3½, 4, 4½, 5, 6, 8, 10, 12, 16, 24, and 36 hours post dosing |
| 9. Study Results | |
| Brief summary of study results | All subjects completed the study. Test product (Ascardia®) was BIOEQUIVALENT to the reference product (Cardio Aspirin®) |
| Date of results summaries | 13-02-2024 |
| Participant flow | Before participating in the study, subject signed an informed consent and undertook an initial medical screening and clinical laboratory tests. After being enrolled, subjects came to Econolab a day before for quarantine. All subjects fasted for at least ten (10) hours prior to drug administration. On the next day, the Responsible Physician instructed subjects to take ofive (5) enteric coated tablet of test product or four (4) enteric coated tablet reference product with 240 mL of water or equivalent to a glass of mineral water. Blood samples were taken from each subject at predose (control) and at-½, 1, 1½, 2, 2½, 3, 3½, 4, 4½, 5, 6, 8, 10, 12, 16, 24, and 36 hours post dosing. Monitoring on vital signs (blood pressure, pulse and respiratory rate, and body temperature) and side effects was done during pre-dose period, immediately after first sampling (½), 2, 4, 6, 12, 24, and 36 hours post drug administration. After one week of washout period, subjects underwent the second period of the study. The second period was carried out with the same procedure as the first period, except the investigational product administered to the subjects was the alternate (test/reference) from the first period. |
| Baseline characteristic | |
| Adverse events | There were 4 mild adverse events occurred during the study. One subject experienced nausea, and one subject experienced headache in the study arm. The same events also happened in the control arm. Headache experienced by subjects in both arms were probably correlated with the study drug while nausea were uncertainly correlated. all subjects recovered without treatment. |
| Outcome measures | Cmax: 106.89% (101.22 – 112.87%)
AUC0-t: 100.40% (94.83 – 106.29%) |
| 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 | |