Bioequivalence study of Pyrazinamide 500 mg tablet manufactured by PT Promedrahardjo Farmasi Industri in comparison with Pyrazinamide 500 mg film coated tablet, Pyrafat® manufactured by SW Pharma GmbH for RIEMSER Pharma GmbH, Schiffweiler - Germany
| 1. Background | |
|---|---|
| Registration Number | INA-96LF5X2 |
| Date of registry approval | 14-11-2023 |
| Registration Date | 05-10-2023 |
| Secondary identifiers | Yes |
| Name of issuing authority (for example protocol number, other registries, etc) | |
| Secondary identifier number | 024/BE/MAR-2023 |
| Scientific study title | Bioequivalence study of Pyrazinamide 500 mg tablet manufactured by PT Promedrahardjo Farmasi Industri in comparison with Pyrazinamide 500 mg film coated tablet, Pyrafat® manufactured by SW Pharma GmbH for RIEMSER Pharma GmbH, Schiffweiler - Germany |
| Public (popular study title) | Bioequivalence study of Pyrazinamide 500 mg tablet manufactured by PT Promedrahardjo Farmasi Industri in comparison with Pyrazinamide 500 mg film coated tablet, Pyrafat® manufactured by SW Pharma GmbH for RIEMSER Pharma GmbH, Schiffweiler - Germany |
| 2. Sponsor and Funding | |
| Primary Sponsor | PT Promedrahardjo Farmasi Industri |
| Source(s) of monetary or material support | PT Promedrahardjo Farmasi Industri |
| Other partners | PT Biometrik Riset Indonesia |
| 3. Contact details | |
| Principal Investigator | |
| Principal investigator | apt. Dra. Effi Setiawati, M.M., M.Biomed. |
| City | Depok |
| Country | Indonesia |
| Principal investigator's affiliation | PT Biometrik Riset Indonesia |
| Principal Investigator's email address | effi@biometrikriset.com |
| Public Queries | |
| Contact person name for public queries | Oktaviani Utami Dewi, S.Si - Ass. Manager QA Telp : 0853-2128-8082 e-Mail: oktaviani@biometrikriset.com |
| Address for public queries | Oktaviani Utami Dewi, S.Si - Ass.Manager QA PT Biometrik Riset Indonesia Ruko Brickhouse Jl Raya Bogor Km 31, No.52 Unit H dan I, Kelurahan Cisalak, Kecamatan Sukmajaya, Depok, Jawa Barat 16416. Telp : 0853-2128-8082 e-Mail: oktaviani@biometrikriset.com |
| City | Depok |
| Country | Indonesia |
| ZIP | 16416 |
| Affiliation for public queries | PT Biometrik Riset Indonesia |
| Email address for public queries | Oktaviani Utami Dewi, S.Si - Ass. Manager QA e-Mail: oktaviani@biometrikriset.com |
| Phone number for public queries | 0853-2128-8082 |
| Scientific Queries | |
| Name of Contact for scientific queries | Oktaviani Utami Dewi, S.Si - Ass. Manager QA Telp : 0853-2128-8082 e-Mail: oktaviani@biometrikriset.com |
| Address for scientific queries | Oktaviani Utami Dewi, S.Si - Ass.Manager QA PT Biometrik Riset Indonesia Ruko Brickhouse Jl Raya Bogor Km 31, No.52 Unit H dan I, Kelurahan Cisalak, Kecamatan Sukmajaya, Depok, Jawa Barat 16416. Telp : 0853-2128-8082 e-Mail: oktaviani@biometrikriset.com |
| City | Depok |
| Country | Indonesia |
| ZIP | 16416 |
| Affiliation of scientific queries contact | PT Biometrik Riset Indonesia |
| Email address for scientific queries | oktaviani@biometrikriset.com |
| 4. IRB & Regulatory | |
| Ethical Approval number | Versi 1.00 : KET-687/UN2.F1/ETIK/PPM.00.02/2023 Versi 1.01 : S-419/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 | 03-07-2023 |
| 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.01.02.321.07.23.01897/UB |
| 5. Status | |
| Countries of recruitment | Indonesia |
| Study sites in Indonesia | PT Biometrik Riset Indonesia |
| Recruitment status | Complete |
| Date of first enrollment | 07-08-2023 |
| Targeted Sample size | 24000 - |
| Number of enrolled participants | 24 |
| Date of study completion (last participant, last visit) | 17-08-2023 |
| 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) | Pyrazinamide 500 mg tablet manufactured by PT Promedrahardjo Farmasi Industri |
| Control intervention (control arm) | Pyrazinamide 500 mg film coated tablet, Pyrafat® manufactured by SW Pharma GmbH for RIEMSER Pharma GmbH, Schiffweiler - Germany |
| Intervention assignment | Crossover |
| 7. Eligibility Criteria | |
| Gender inclusion criteria | Not specified |
| Minimum age | 18 |
| Maximum age | 55 |
| Inclusion criteria | a.Willing to participate and agree to sign informed consent and communicate well with the investigators.
b.Healthy female/male subjects as determined by the medical screening assessments. c.Aged 18 - 55 years inclusive. d.Body mass index within the range of 18.00 - 25.00 kg/m2. e.Vital signs, after 10 minutes resting, within the following ranges: (i).Pulse rate: 60 - 90 bpm. (ii).Respiratory Rate: 12 - 20 x/minutes. (iii).Systolic blood pressure: 110 - 129 mmHg. (iv).Diastolic blood pressure: 70 - 84 mmHg. (v).Body temperature < 37.5°C f.Have 12-lead ECG without significant abnormalities. g.Do not have symptoms of Covid-19 and a history of close contact with Covid-19 patients h.Have received the primary SARS-CoV-2 vaccine complete and at least the first booster. |
| Exclusion criteria | a.Participate in another study within 3 (three) months prior to the first day of study drug administration.
b.Pregnant or lactating female (urinary pregnancy test will be performed on screening day and prior study drug administrations on each period). c.Smoker or smoking more than 10 (ten) cigarettes per day. d.Intake of any prescription drug or non-prescription drug within 7 days prior to the first day of drug administration of this study. e.Blood donation or blood loss of 300 mL (or more) within 3 (three) months prior to the first day of study drug administration. f.History of drug and/or alcohol abuse or dependency within 12 months prior to the first day of study drug administration. g.Known hypersensitivity or contraindication to the study drug. h.Any surgical or medical condition (present or history) which might significantly alter the absorption, distribution, metabolism or excretion of the study, e.g. gastrointestinal disease including gastric or duodenal ulcers or history of gastric surgery. i.History of any bleeding or coagulative disorders. j.Clinically significant hematology abnormalities. k.Clinically significant urinalysis abnormalities. l.Renal insufficiency (plasma’s creatinine concentration ≥ 1.50 mg/dL). m.History or presence of any liver dysfunction (SGPT, SGOT, alkaline phosphate, total bilirubin ≥ 1.5 ULN). n.Positive result of HBsAg, HCV, and/or HIV test |
| 8. Study Outcome | |
| Primary Outcome | |
| Name of primary outcome | AUC0-t , Cmax |
| Metric/method of measurement | Statistical analysis with Anova using Phoenix WinNonlin Version 8.3 (Certara L.P., St. Louis, MO, USA) |
| Timepoint(s) of measurement | Predose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours |
| Secondary outcome 1 | |
| Name of secondary outcome 1 (SO1) | AUC0-inf , Tmax, Half life |
| Metric/method of measurement (SO1) | Statistical analysis with Anova using Phoenix WinNonlin Version 8.3 (Certara L.P., St. Louis, MO, USA) |
| Timepoint(s) of measurement (SO1) | Predose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours |
| 9. Study Results | |
| Brief summary of study results | Since the 90% Confidence Interval (CI) with α = 5.00% for AUC0-48h and Cmax were within the range of 80.00 - 125.00% interval, it was concluded the test drug Pyrazinamide (BN: R004C23P-1) manufactured by PT Promedrahardjo Farmasi Industri BIOEQUIVALENCE in term of both rate and extent of absorption to the reference drug Pyrafat® (BN: 001022) manufactured by SW Pharma GmbH for RIEMSER Pharma GmbH, Schiffweiler - Germany. |
| Date of results summaries | 19-09-2023 |
| Participant flow | 37 Subjek mengikuti kegiatan briefing
37 Subjek mengikuti kegiatan informed consent, skrining pemeriksaan fisik 33 subjek mengikuti pemeriksaan ekg 33 Subjek mengikuti pemeriksaan imunologi, darah dan urin 24 subjek mengikuti kegiatan sampling |
| Baseline characteristic | |
| Adverse events | Tidak ada adverse event |
| Outcome measures | Parameters Geometric Mean Ratio (GMR) T/R (%) 90% Confidence Interval
(CI) (%) Coefficient of Variation (%) Power Study (%) Lower Upper AUC0-t (ng.h/mL) 101.72 95.45 108.40 12.89 99.99 Cmax (ng/mL) 100.51 96.54 104.64 8.14 100.00 AUC0-Inf (ng.h/mL) 101.92 95.62 108.62 12.91 99.99 |
| 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)) | Undecided |
| Plan for IPD sharing (what IPD will be shared, when, by what mechanism, with whom, and for what types of analyses) | |
| Other important informations | - |