Bioequivalence Study of Tenofovir Disoproxil Fumarate/ Lamivudine/ Efavirenz 300 mg/ 300 mg/ 600 mg Film Coated Tablets manufactured by PT Kimia Farma Tbk in comparison with Tenofovir Disoproxil Fumarate/ Lamivudine/ Efavirenz 300 mg/ 300 mg/ 600 mg Tablet, Symfi® manufactured by Mylan Laboratories Limited Hyderabad India for Mylan Specialty L.P. Morgantown, WV 26505 U.S.A; registered trademark of Mylan Pharmaceuticals inc.
| 1. Background | |
|---|---|
| Registration Number | INA-WTY4FQX |
| Date of registry approval | 22-04-2024 |
| Registration Date | 18-04-2024 |
| Secondary identifiers | No |
| Name of issuing authority (for example protocol number, other registries, etc) | |
| Secondary identifier number | |
| Scientific study title | Bioequivalence Study of Tenofovir Disoproxil Fumarate/ Lamivudine/ Efavirenz 300 mg/ 300 mg/ 600 mg Film Coated Tablets manufactured by PT Kimia Farma Tbk in comparison with Tenofovir Disoproxil Fumarate/ Lamivudine/ Efavirenz 300 mg/ 300 mg/ 600 mg Tablet, Symfi® manufactured by Mylan Laboratories Limited Hyderabad India for Mylan Specialty L.P. Morgantown, WV 26505 U.S.A; registered trademark of Mylan Pharmaceuticals inc. |
| Public (popular study title) | Bioequivalence Study of Tenofovir Disoproxil Fumarate/ Lamivudine/ Efavirenz 300 mg/ 300 mg/ 600 mg Film Coated Tablets manufactured by PT Kimia Farma Tbk in comparison with Tenofovir Disoproxil Fumarate/ Lamivudine/ Efavirenz 300 mg/ 300 mg/ 600 mg Tablet, Symfi® manufactured by Mylan Laboratories Limited Hyderabad India for Mylan Specialty L.P. Morgantown, WV 26505 U.S.A; registered trademark of Mylan Pharmaceuticals inc. |
| 2. Sponsor and Funding | |
| Primary Sponsor | PT Kimia Farma Tbk |
| Source(s) of monetary or material support | PT Kimia Farma Tbk |
| 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 | e-Mail: oktaviani@biometrikriset.com |
| 4. IRB & Regulatory | |
| Ethical Approval number | KET-1345/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 | 09-10-2023 |
| 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.01.02.321.10.23.02152/UB |
| 5. Status | |
| Countries of recruitment | Indonesia |
| Study sites in Indonesia | PT Biometrik Riset Indonesia |
| Recruitment status | Complete |
| Date of first enrollment | 04-11-2023 |
| Targeted Sample size | 00030 - |
| Number of enrolled participants | 29 |
| Date of study completion (last participant, last visit) | 31-12-2023 |
| 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) | Tenofovir Disoproxil Fumarate/ Lamivudine/ Efavirenz 300 mg/ 300 mg/ 600 mg Film Coated Tablets manufactured by PT Kimia Farma Tbk |
| Control intervention (control arm) | Tenofovir Disoproxil Fumarate/ Lamivudine/ Efavirenz 300 mg/ 300 mg/ 600 mg Tablet, Symfi® manufactured by Mylan Laboratories Limited Hyderabad India for Mylan Specialty L.P. Morgantown, WV 26505 U.S.A; registered trademark of Mylan Pharmaceuticals inc. |
| Intervention assignment | Other |
| 7. Eligibility Criteria | |
| Gender inclusion criteria | Not specified |
| Minimum age | 18 |
| Maximum age | 55 |
| Inclusion criteria | a. Willing to participate and agree to sign the 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: 100 - 129 mmHg. (iv). Diastolic blood pressure: 60 - 84 mmHg. (v). Body temperature < 37.5°C f. Have 12-lead ECG without significant abnormalities. g. Willing to use protection (condoms) when having sex during the bioequivalence study. h. Do not have symptoms of Covid-19 and a history of close contact with Covid-19 patients i. Have received the primary SARS-CoV-2 vaccine complete and at least the first booster. j. 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, 5, 6, 9, 12, 24, 48, and 72 hours after dosing |
| 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, 5, 6, 9, 12, 24, 48, and 72 hours after dosing |
| 9. Study Results | |
| Brief summary of study results | Since the 90% Confidence Interval (CI) with α = 5.00% for AUC0-72h and Cmax were within the range of 80.00 - 125.00% interval, it was concluded the test drug [Ta] Tenofovir Disoproxil Fumarate Lamivudine/ Efavirenz (BN: J03G3485) and test drug [Tb] Tenofovir Disoproxil Fumarate/ Lamivudine Efavirenz (BN: J03G3487) manufactured by PT Kimia Farma Tbk is BIOEQUIVALENCE in term of both rate and extent of absorption to the reference drug Symfi® (BN: 3132415) manufactured by Mylan Laboratories Limited Hyderabad India for Mylan Specialty L.P. Morgantown, WV 26505 U.S.A; registered trademark of Mylan Pharmaceuticals inc.. |
| Date of results summaries | 03-04-2024 |
| Participant flow | The bioequivalence study was carried out on 30 (thirty) healthy subjects, which consist of 20 (twenty) male subjects and 10 (ten) female subjects. The number of subjects who finished the study was 29 (twenty-nine) subjects, where subject S17 dropped out from this study in the 2nd period because of lost to follow up. |
| Baseline characteristic | |
| Adverse events | There was no adverse events that occurred during this study. |
| Outcome measures | Tenofovir:
Parameters Geometric Mean Ratio (GMR) T/R (%) 90% Confidence Interval (CI) (%) Coefficient of Variation (%) Power Study (%) Lower Upper AUC 0-t (ng.h/mL) 94.65 85.59 104.67 22.77 97.61 C max (ng/mL) 91.81 83.80 100.57 20.59 98.98 AUC 0-Inf (ng.h/mL) 95.06 86.18 104.86 22.18 98.06 Lamivudine: Parameters Geometric Mean Ratio (GMR) T/R (%) 90% Confidence Interval (CI) (%) Coefficient of Variation (%) Power Study (%) Lower Upper AUC 0-t (ng.h/mL) 95.73 87.06 105.27 21.46 98.53 C max (ng/mL) 93.34 86.29 100.96 17.68 99.80 AUC 0-Inf (ng.h/mL) 95.58 87.16 104.83 20.85 98.86 Efavirenz: Parameters Geometric Mean Ratio (GMR) T/R (%) 90% Confidence Interval (CI) (%) Coefficient of Variation (%) Power Study (%) Lower Upper AUC 0-t (ng.h/mL) 96.51 89.09 104.56 18.04 99.74 C max (ng/mL) 88.77 80.70 97.64 21.54 98.49 AUC 0-Inf (ng.h/mL) 94.75 80.03 112.16 39.11 70.65 |
| 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 | N/A |