Bioequivalence Study of 90 mg Ticagrelor Film Coated Tablets Produced by PT. Novell Pharmaceutical Laboratories In Comparison with Brilinta® 90 mg Film Coated Tablets Manufactured by AstraZeneca AB, Sweden, Packed and Released by AstraZeneca Pharmaceutical Co., Ltd., China, Imported by PT. AstraZeneca Indonesia
| 1. Background | |
|---|---|
| Registration Number | INA-6XR43T9 |
| Date of registry approval | 22-04-2024 |
| Registration Date | 17-04-2024 |
| Secondary identifiers | No |
| Name of issuing authority (for example protocol number, other registries, etc) | |
| Secondary identifier number | |
| Scientific study title | Bioequivalence Study of 90 mg Ticagrelor Film Coated Tablets Produced by PT. Novell Pharmaceutical Laboratories In Comparison with Brilinta® 90 mg Film Coated Tablets Manufactured by AstraZeneca AB, Sweden, Packed and Released by AstraZeneca Pharmaceutical Co., Ltd., China, Imported by PT. AstraZeneca Indonesia |
| Public (popular study title) | Bioequivalence Study of 90 mg Ticagrelor Film Coated Tablets Produced by PT. Novell Pharmaceutical Laboratories In Comparison with Brilinta® 90 mg Film Coated Tablets Manufactured by AstraZeneca AB, Sweden, Packed and Released by AstraZeneca Pharmaceutical Co., Ltd., China, Imported by PT. AstraZeneca Indonesia |
| 2. Sponsor and Funding | |
| Primary Sponsor | PT. Novell Pharmaceutical Laboratories |
| Source(s) of monetary or material support | PT. Novell Pharmaceutical Laboratories |
| Other partners | PT Clinisindo Laboratories |
| 3. Contact details | |
| Principal Investigator | |
| Principal investigator | Prof. Dr. apt. Yahdiana Harahap, MS |
| City | Jakarta Selatan |
| Country | Indonesia |
| Principal investigator's affiliation | PT Clinisindo Laboratories |
| Principal Investigator's email address | Yahdiana03@yahoo.com |
| Public Queries | |
| Contact person name for public queries | Apt. Windy Lusthom, S.Si – Study Director Telp : (62-21) 73889918, e-Mail: Windy.Lusthom@clinisindo.com |
| Address for public queries | Apt. Windy Lusthom, S.Si – Study Director PT Clinisindo Laboratories Jl. Ulujami Raya No.12, Pesanggrahan, Jakarta Selatan 12250, Indonesia Telp : (62-21) 73889918, e-Mail: Windy.Lusthom@clinisindo.com |
| City | Jakarta Selatan |
| Country | Indonesia |
| ZIP | 12250 |
| Affiliation for public queries | PT Clinisindo Laboratories |
| Email address for public queries | Apt. Windy Lusthom, S.Si – Study Director e-Mail: Windy.Lusthom@clinisindo.com |
| Phone number for public queries | (62-21) 73889918 |
| Scientific Queries | |
| Name of Contact for scientific queries | Apt. Windy Lusthom, S.Si – Study Director Telp : (62-21) 73889918, e-Mail: Windy.Lusthom@clinisindo.com |
| Address for scientific queries | Apt. Windy Lusthom, S.Si – Study Director PT Clinisindo Laboratories Jl. Ulujami Raya No.12, Pesanggrahan, Jakarta Selatan 12250, Indonesia Telp : (62-21) 73889918, e-Mail: Windy.Lusthom@clinisindo.com |
| City | Jakarta Selatan |
| Country | Indonesia |
| ZIP | 12250 |
| Affiliation of scientific queries contact | PT Clinisindo Laboratories |
| Email address for scientific queries | windy.lusthom@clinisindo.com |
| 4. IRB & Regulatory | |
| Ethical Approval number | KET-90/UN2.F1/ETIK/PPM.00.02/2023 |
| Name of Ethics committee | Komite Etik Penelitian Kesehatan Fakultas Kedokteran Universitas Indonesia –RSUPN Dr. Cipto Mangunkusumo |
| Date of Ethic approval | 16-01-2023 |
| Contact details of Ethic Committee (phone, email, and office) | Komite Etik FKUI/RSCM Jl. Salemba 6, Jakarta Pusat Whatsapp : 0856-8701-608 Telp. 021 315 7008 E-mail :ec_fkui@yahoo.com |
| Number of Persetujuan Pelaksanaan Uji Klinik (PPUK)/Persetujuan Protokol Uji BE (PPUB) | RG.01.02.321.09.23.02069/UB |
| 5. Status | |
| Countries of recruitment | Indonesia |
| Study sites in Indonesia | PT. Clinisindo Laboratories |
| Recruitment status | Complete |
| Date of first enrollment | 08-12-2023 |
| Targeted Sample size | 00024 - |
| Number of enrolled participants | 27 |
| Date of study completion (last participant, last visit) | 20-12-2023 |
| 6. Study Design & Purpose | |
| Primary health condition(s) or problem(s) studied (e.g., depression, breast cancer,medication error) | Study in healthy human volunteers |
| Purpose of the study | Bioequivalence study |
| 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) | Ticagrelor Film Coated Tablets Produced by PT. Novell Pharmaceutical Laboratories |
| Control intervention (control arm) | Ticagrelor 90 mg Film Coated Tablets, Brilinta® Manufactured by AstraZeneca AB, Sweden, Packed and Released by AstraZeneca Pharmaceutical Co., Ltd., China, Imported by PT. AstraZeneca Indonesia |
| Intervention assignment | Crossover |
| 7. Eligibility Criteria | |
| Gender inclusion criteria | Not specified |
| Minimum age | 18 |
| Maximum age | 55 |
| Inclusion criteria | Give a written informed consent, healthy subjects, both sexes, age between 18 to 55 years old, weight with the normal range according to accepted normal values for the Body Mass Index (BMI = 18-25 kg/m2), accepted normal values of blood pressure (systolic blood pressure 90 mmHg, diastolic blood pressure 60 mmHg) and heart rate (60-90 bpm), acceptable medical history and physical examination, normal hematology values including: hemoglobin, hematocrit, erythrocyte, leukocyte, mean corpuscular (MC) values, leukocyte differential, platelets count and erythrocyte sedimentation rate (ESR), normal laboratory tests including: sGPT, sGOT, alkaline phosphatase, total bilirubin, total protein, albumin, globulin, blood glucose, blood urea nitrogen, ureum, creatinine, normal urinalysis results including: color, clarity, specific gravity, pH, leukocyte esterase, nitrite, glucose, keton, urobilinogen, bilirubin, blood and urine sediments (cells, casts, and bacteria), normal cardiovascular function proven by electrocardiogram (ECG) result, negative result for serological tests of hepatitis B antigen (HBsAg), Hepatitis C (anti HCV), HIV (anti HIV), negative result for drug of abuse tests of amphetamine, metamphetamine, morphine, marijuana/tetrahydrocannabinol (THC), and benzodiazepine, negative result for pregnancy test (will be done for female subjects at screening, before period I and before period II of the study), subject has either received COVID-19 (Coronavirus) vaccine minimum of first booster or negative result for rapid antigen test of COVID-19 at screening.
Note: * The clinical investigator might include a subject having value outside the accepted range, if in his/her opinion, these values were not clinically significant. |
| Exclusion criteria | Smoker. If necessary, light smoker (≤5 cigarettes/day) can be accepted, Pregnant women or nursing mother,Have history of hepatic, cardiovascular, gastrointestinal or renal disease, Have history or condition of intracranial hemorrhage or stroke, ave history or condition of active pathological bleeding such as peptic ulcer or intracranial hemorrhage, Have history or condition of severe hepatic impairment, Have history or condition of bleeding disorder, Have history of performance of percutaneous invasive procedure, Have history or condition of dyspnea Have schedule of any surgery during participation in this study, Have risk of bradyarrhythmia/bradycardic events, Hypersensitivity to ticagrelor or similar medication, History of alcohol, drug abuse within 12 months prior to screening for this stud, Received any other medications within fourteen days prior to the start of the study, Participated in any clinical study within 3 months after the date of completion, Donation or loss more than 300 mL of blood within 3 months prior to the screening of the study. |
| 8. Study Outcome | |
| Primary Outcome | |
| Name of primary outcome | AUC0-t , AUC0-inf , Cmax |
| Metric/method of measurement | Statistical analysis with Anova using Microsoft® Excel 2010, EquivTest® version 2.0 and SAS® version 9.1 |
| Timepoint(s) of measurement | Pre dose, at 20, 40 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36 hours after drug administration |
| Secondary outcome 1 | |
| Name of secondary outcome 1 (SO1) | Tmax, Half life |
| Metric/method of measurement (SO1) | Statistical analysis with Anova using Microsoft® Excel 2010, EquivTest® version 2.0 and SAS® version 9.1 |
| Timepoint(s) of measurement (SO1) | Pre dose, at 20, 40 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36 hours after drug administration |
| 9. Study Results | |
| Brief summary of study results | In conclusion, the application of parametric and non-parametric statistics reveal the presence of bioequivalence between 90 mg Ticagrelor film coated tablets produced by PT. Novell Pharmaceutical Laboratories in comparison with Brilinta® 90 mg film coated tablets manufactured by AstraZeneca AB, Sweden, packed and released by AstraZeneca Pharmaceutical Co., Ltd., China, imported by PT. AstraZeneca Indonesia. Thus, it can be assumed that the two formulations were therapeutically equivalent and therefore interchangeable. |
| Date of results summaries | 04-03-2024 |
| Participant flow | During the screening period of the study, 42 (forty-two) subjects were screened after had signed an Informed Consent Form. There were 15 (fifteen) subjects who failed during screening period.
Twenty-seven (27) subjects were randomized and enrolled. This study was performed in accordance with health protocol during COVID-19 pandemic and applicable in-house SOP. There was 1 (one) subject discontinued in the study; S27 was withdrawn by clinical investigator before period I due to Covid-19 rapid test positive result. During sampling, 26 (twenty-six) subjects completed both periods of the study. The safety analysis was performed on 26 (twenty-six) subjects who had received at least one of the study drug (test or reference formulation). Finally, the pharmacokinetic and statistical analysis were performed on 26 (twenty-six) subjects, who had completed both periods of the study. |
| Baseline characteristic | |
| Adverse events | Subjects treated in the study reported a total 40 adverse events. The events reported were hypotension (13 events), prehypertension (13 events), bradycardia (10 events), nausea (2 events), dizziness (1 event), and tachycardia (1 event). All adverse events were also resolved completely without any concomitant medications. There was no serious adverse event. |
| Outcome measures | The 90% Confidence Interval (CI) with α = 5.00% for AUC0-48h and Cmax were within the range of 80.00 - 125.00% interval |
| 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 | - |