Bioequivalence Study of Mesalazine 500 mg Enteric Coated Tablet, Kolozin® Manufactured by PT Interbat in Comparison with Mesalazine 500 mg Enteric Coated Tablet, Salofalk® Manufactured by Losan Pharma GMBH, Germany; for Dr. Falk Pharma GMBH, Germany; Imported and Marketed by PT Darya-Varia Laboratoria Tbk, Indonesia under Fasting Condition
| 1. Background | |
|---|---|
| Registration Number | INA-565770GN |
| Date of registry approval | 25-06-2025 |
| Registration Date | 23-06-2025 |
| Secondary identifiers | Yes |
| Name of issuing authority (for example protocol number, other registries, etc) | Yes, protocol number : 070/BE/AUG-2024 |
| Secondary identifier number | 070/BE/AUG-2024 |
| Scientific study title | Bioequivalence Study of Mesalazine 500 mg Enteric Coated Tablet, Kolozin® Manufactured by PT Interbat in Comparison with Mesalazine 500 mg Enteric Coated Tablet, Salofalk® Manufactured by Losan Pharma GMBH, Germany; for Dr. Falk Pharma GMBH, Germany; Imported and Marketed by PT Darya-Varia Laboratoria Tbk, Indonesia under Fasting Condition |
| Public (popular study title) | Bioequivalence Study of Mesalazine 500 mg Enteric Coated Tablet, Kolozin® Manufactured by PT Interbat in Comparison with Mesalazine 500 mg Enteric Coated Tablet, Salofalk® Manufactured by Losan Pharma GMBH, Germany; for Dr. Falk Pharma GMBH, Germany; Imported and Marketed by PT Darya-Varia Laboratoria Tbk, Indonesia under Fasting Condition |
| 2. Sponsor and Funding | |
| Primary Sponsor | PT Interbat |
| Source(s) of monetary or material support | Sponsor : PT Interbat |
| 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 |
| 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@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 |
| 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 | KET-1715/UN2.F1/ETIK/PPM.00.02/2024 |
| Name of Ethics committee | Komite Etik Penelitian Kesehatan Fakultas Kedokteran Universitas Indonesia –RSUPN Dr. Cipto Mangunkusumo |
| Date of Ethic approval | 22-11-2024 |
| 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.01.02.321.03.25.03442/UB |
| 5. Status | |
| Countries of recruitment | Indonesia |
| Study sites in Indonesia | PT Biometrik Riset Indonesia |
| Recruitment status | Complete |
| Date of first enrollment | 11-04-2025 |
| Targeted Sample size | 00024 - |
| Number of enrolled participants | 24 |
| Date of study completion (last participant, last visit) | 06-05-2025 |
| 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) | Mesalazine 500 mg Enteric Coated Tablet, Kolozin® Manufactured by PT Interbat |
| Control intervention (control arm) | Salofalk® Manufactured by Losan Pharma GMBH, Germany; for Dr. Falk Pharma GMBH, Germany; Imported and Marketed by PT Darya-Varia Laboratoria Tbk, Indonesia |
| 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 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 (based on ECG examination). (ii). Respiratory Rate: 12 - 20 x/minutes. (i). Systolic blood pressure: 100 - 129 mmHg. (ii). Diastolic blood pressure: 60 - 84 mmHg. (iii). Body temperature < 37.5°C f. Have 12-lead ECG without significant abnormalities. g. Willing to abstinence or used contraception during the study. |
| 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 or other NSAIDs or allied 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 8.5 (Certara L.P., St. Louis, MO, USA) based on the Reference-Scaled Average Bioequivalence (RSABE) approach. |
| Timepoint(s) of measurement | predose, 1, 2, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 12, 16, 24, 48 and 72 hours after dosing |
| Secondary outcome 1 | |
| Name of secondary outcome 1 (SO1) | AUC0-inf, AUC8-48, Tmax, Half life |
| Metric/method of measurement (SO1) | Statistical analysis with Anova using Phoenix WinNonlin Version 8.5 (Certara L.P., St. Louis, MO, USA) |
| Timepoint(s) of measurement (SO1) | predose, 1, 2, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 12, 16, 24, 48 and 72 hours after dosing |
| 9. Study Results | |
| Brief summary of study results | Since the requirement acceptance of Reference-Scaled Average Bioequivalence (RSABE) for AUC0-72h and Cmax were within the criteria of Swr ≥ 0.294, i.e the 95% upper confidence bound for (ῩT - ῩR)2 – θS2WR ≤ 0 and the point estimate of the test/reference geometric mean ratio is within the range of 0.80–1.25. It was concluded the test drug Kolozin® (BN: ZT1397402) manufactured by PT Interbat is BIOEQUIVALENCE in term of both rate and extent of absorption to the reference drug Salofalk® (BN: L23143A) manufactured by Losan Pharma GMBH, Germany; for Dr. Falk Pharma GMBH, Germany; imported and marketed by PT Darya-Varia Laboratoria Tbk, Indonesia. |
| Date of results summaries | 05-06-2025 |
| Participant flow | 53 Subjek mengikuti kegiatan briefing
53 Subjek mengikuti kegiatan informed consent 37 Subjek mengikuti skrining pemeriksaan fisik 31 Subjek mengikuti pemeriksaan ekg 31 Subjek mengikuti pemeriksaan immunologi. darah dan urin 24 subjek mengikuti kegiatan sampling 23 subjek mengikuti sampling periode 2 sampai selesai |
| Baseline characteristic | |
| Adverse events | N/A |
| Outcome measures | AUC0-T:
Swr : 0.56 PE : 1.04 Critical Bound : -0.16 Cmax: Swr : 0.85 PE : 1.21 Critical Bound : -0.28 |
| 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 | Not Specified |