Bioequivalence Study of 100 mg Sitagliptin Film-Coated Film-coated tablets Manufactured by PT. Tropica Mas Pharmaceuticals in Comparison with 100 mg Januvia™ Film-Coated Film-coated tablets Manufactured by Merck Sharp & Dohme Ltd., Cramlington, England, Registered and Packed by PT. Merck Sharp Dohme Pharma Tbk, Pasuruan, Indonesia
| 1. Background | |
|---|---|
| Registration Number | INA-H7BTHKZ |
| Date of registry approval | 17-01-2024 |
| Registration Date | 10-01-2024 |
| Secondary identifiers | Yes |
| Name of issuing authority (for example protocol number, other registries, etc) | 649/STD/PML/2021 |
| Secondary identifier number | 649/STD/PML/2021 |
| Scientific study title | Bioequivalence Study of 100 mg Sitagliptin Film-Coated Film-coated tablets Manufactured by PT. Tropica Mas Pharmaceuticals in Comparison with 100 mg Januvia™ Film-Coated Film-coated tablets Manufactured by Merck Sharp & Dohme Ltd., Cramlington, England, Registered and Packed by PT. Merck Sharp Dohme Pharma Tbk, Pasuruan, Indonesia |
| Public (popular study title) | Bioequivalence Study of 100 mg Sitagliptin Film-Coated Film-coated tablets Manufactured by PT. Tropica Mas Pharmaceuticals in Comparison with 100 mg Januvia™ Film-Coated Film-coated tablets Manufactured by Merck Sharp & Dohme Ltd., Cramlington, England, Registered and Packed by PT. Merck Sharp Dohme Pharma Tbk, Pasuruan, Indonesia |
| 2. Sponsor and Funding | |
| Primary Sponsor | PT. Tropica Mas Pharmaceuticals |
| Source(s) of monetary or material support | PT. Tropica Mas Pharmaceuticals |
| Other partners | PT. Pharma Metric Labs |
| 3. Contact details | |
| Principal Investigator | |
| Principal investigator | Metta Sinta Sari Wiria, Pharm, MS |
| City | Jakarta Pusat |
| Country | Indonesia |
| Principal investigator's affiliation | PT. Pharma Metric Labs |
| Principal Investigator's email address | msswiria@gmail.com |
| Public Queries | |
| Contact person name for public queries | Nabila Mudin Sutanto |
| Address for public queries | PT. Pharma Metric Labs Gedung Indra Sentral Cempaka Putih Unit R-U Jalan Letjen Suprapto Kav. 60 Central Jakarta, 10520 Indonesia |
| City | Jakarta |
| Country | Indonesia |
| ZIP | 10520 |
| Affiliation for public queries | PT. Pharma Metric Labs |
| Email address for public queries | nabila.pmlabs@gmail.com |
| Phone number for public queries | +62214265310 |
| Scientific Queries | |
| Name of Contact for scientific queries | I Gusti Putu Bagus Diana Virgo, Pharm |
| Address for scientific queries | PT. Pharma Metric Labs Gedung Indra Sentral Cempaka Putih Unit R-U Jalan Letjen Suprapto Kav. 60 Central Jakarta, 10520 Indonesia |
| City | Jakarta |
| Country | Indonesia |
| ZIP | 10520 |
| Affiliation of scientific queries contact | PT. Pharma Metric Labs |
| Email address for scientific queries | gusti.virgo@pharmametriclabs.com |
| 4. IRB & Regulatory | |
| Ethical Approval number | KET-89/UN2.F1/ETIK/PPM.00.02/2022 |
| Name of Ethics committee | Komite Etik Penelitian Kesehatan Fakultas Kedokteran Universitas Indonesia |
| Date of Ethic approval | 31-01-2022 |
| Contact details of Ethic Committee (phone, email, and office) | Gedung fakultas Kedokteran UI Jl. Salemba Raya No. 6, Jakarta 10430 PO.Box 1358 Telepon : +62213912477 Email : humas@fk.ui.ac.id |
| Number of Persetujuan Pelaksanaan Uji Klinik (PPUK)/Persetujuan Protokol Uji BE (PPUB) | RG.01.02.321.04.22.00876/UB |
| 5. Status | |
| Countries of recruitment | Indonesia |
| Study sites in Indonesia | PT Pharma Metric Labs |
| Recruitment status | Complete |
| Date of first enrollment | 16-05-2022 |
| Targeted Sample size | 00020 - |
| Number of enrolled participants | 20 |
| Date of study completion (last participant, last visit) | 26-05-2022 |
| 6. Study Design & Purpose | |
| Primary health condition(s) or problem(s) studied (e.g., depression, breast cancer,medication error) | healthy human volunteers |
| Purpose of the study | Bioequivalent 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) | Sitagliptin 100 mg film-coated tablets |
| Control intervention (control arm) | Januvia™ 100 mg film-coated tablets |
| Intervention assignment | Crossover |
| 7. Eligibility Criteria | |
| Gender inclusion criteria | Male, Female |
| Minimum age | 18 |
| Maximum age | 55 |
| Inclusion criteria | Healthy male or female subjects, subject had read the subject information and signed informed consent documents, age range of subject from 18 – 55 years, body mass index between 18 – 25 kg/m2, subject had a normal electrocardiogram, subject had the blood pressure within normal range (systolic 90-120 mmHg and diastolic 60-80 mmHg), subject had the heart rate within normal range (60 – 100 bpm), subject had absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening, subject agreed to use protection (condom) before any intercourse with their spouse throughout the study |
| Exclusion criteria | Those who were pregnant and/or nursing women, those with history of contraindication or hypersensitivity to sitagliptin , or other antidiabetic agent, or other ingredients in the study products, or a history of serious allergic reaction to any drug, a significant allergic disease or allergic reaction, those with a history or presence of medical condition which might significantly influence the pharmacokinetic of the study drug, e.g. chronic gastrointestinal disease, diarrhea, gastric surgery, renal insufficiency, hepatic dysfunction or cardiovascular disease, those with a history or presence of any coagulation disorder or clinically significant hematology abnormalities, those who were using any medication (prescription or non-prescription drug, food supplement, herbal medicine), particularly the medication known to affect the pharmacokinetic of the study drug, within one week prior to the drug administration day, those who participated in any clinical study within 3 months prior to the study ( |
| 8. Study Outcome | |
| Primary Outcome | |
| Name of primary outcome | Cmax and AUCt |
| Metric/method of measurement | The plasma concentrations of sitagliptin were determined by means of LC-MS/MS with a LLOQ of 4.83 ng/mL |
| Timepoint(s) of measurement | Blood samples were drawn prior to study drug administration (0 h), and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 8, 12, 16, 24, 36, and 48 hours after drug administration. |
| 9. Study Results | |
| Brief summary of study results | A bioequivalence study was conducted to investigate whether 100 mg Sitagliptin film-coated tablets manufactured by PT. Tropica Mas Pharmaceuticals was bioequivalent towards its reference product, 100 mg Januvia™ film-coated tablets manufactured by Merck Sharp & Dohme Ltd., Cramlington, England, registered and packed by PT. Merck Sharp Dohme Pharma Tbk, Pasuruan, Indonesia.
This study was designed as a randomized, single-blind, two-period, two-treatment, two-sequence, single dose, cross-over design in 20 healthy subjects under fasted condition. The subjects age ranged from 28 to 53 years, with normal body weight (body mass index 18.61 – 24.22 kg/m2), normal or not clinically significant blood pressure range (systolic blood pressure within 92 – 120 mmHg and diastolic blood pressure within 62 – 80 mmHg), with normal heart rate (60 – 99 bpm) and normal electrocardiogram, with absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening, agreed to use protection (condom) before any intercourse with their spouse during the study and had read the subject information and had signed the informed consent documents. The study was conducted following an oral administration of one tablet of the test drug (100 mg Sitagliptin film-coated tablets) or one tablet of the reference drug (100 mg Januvia® Film-Coated Tablet). Blood samples were drawn before dosing (0 h) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 8, 12, 16, 24, 36 and 48 hours after drug administration. Following a washout period of one week, this procedure was repeated using the alternate drug. From total 20 enrolled subjects, all subject completed the study and statistically evaluated. The plasma concentrations of sitagliptin were determined by a validated LC-MS/MS method with LLoQ 4.83 ng/mL. The pharmacokinetic parameters used in this study were area under the concentration-time curve of Sitagliptin Phosphate from time zero to 48 hours (AUCt) and maximum concentration (Cmax). While secondary parameters used are area under the concentration-time curve from time zero to infinite (AUCinf), time required to reach the maximum concentration (tmax) and the elimination half life (t½). The result from this study, bioequivalence study of 100 mg Sitagliptin film-coated tablets (test product) in comparison with 100 mg Januvia® Film-Coated Tablet (reference drug) were as following: 90% confidence intervals of geometric means ratio of the two bioavailability parameters of sitagliptin were 90.80% - 110.74% for Cmax, 92.79% - 104.74% for AUCt. These results showed that 100 mg Sitagliptin film-coated tablets was bioequivalent towards its reference product, 100 mg Januvia® Film-Coated Tablet. |
| Date of results summaries | 24-06-2022 |
| Participant flow | Subject screening and selection took place prior to the sampling period and only after the subject agreed to participate in the study and the Informed Consent Form has been signed by the subject.
Subject screening was conducted with limited of number of people/subject candidates, with maximum 5 subjects per session. Study team in charge used personal protective equipment that consisted of surgical pants, head cap, face shield, N95 mask, goggles, hand gloves, and shoes’ cover, and the subjects were be asked to use face mask, washed their hands prior to registration/consenting, used the available gloves, and implement physical distancing with a minimal of 1 meter distance among each other during the screening process. The Study Physician informed all the subjects about the details of the study: the objective and the procedure, as well as the study rules to be followed during the study, the possible adverse effects of the drug, and that all subjects were free to withdraw from the study at any stage. The subject information sheet and consent form was provided in the subjects’ first language. Medical history, physical examination, laboratory tests (routine hematology, blood biochemistry and urinalysis), electrocardiograph, pregnancy test and HIV, HBsAg, HCV tests and anti SARS CoV-2 test were carried out to screen the subjects and to obtain eligible subjects who meet the inclusion and exclusion criteria. The Study Coordinator or Study Physician took subjects' demography data which included full name, sex, date of birth, age, address, race, height, weight, and smoking and alcohol consumption habit. The medical history was taken includes systemic review of allergies, family history, and surgical history. The physical examination included overall appearance, eyes, ears, nose, throat, head and neck, heart, lung, abdomen (including liver and spleen), lymph nodes, skin, musculoskeletal, and nervous system examination. The vital signs would also be measured, which include blood pressure, pulse, respiration rate and body temperature. The laboratory tests cover completed hematology (hemoglobin, leucocyte, white blood cell differential counts, erythrocyte, platelet, hematocrit, and erythrocyte sedimentation rate), blood chemistry (alanine aminotransferase/ALT/SGPT, aspartate aminotransferase/AST/SGOT, alkaline phosphatase, bilirubin, blood glucose level, ureum, and creatinine), and urinalysis (density, pH, leucocyte, nitrite, albumin/protein, glucose, ketone (acetone), urobilinogen, bilirubin, and blood count). A total of 15 mL of blood was taken for the laboratory test, including HIV, HBsAg, HCV tests. SARS CoV-2 antigen test was performed by swabbing the subject nasopharynx and examine the sample using provided test kit. Swab antigen SARS-CoV-2 test was carried out also on 1 days prior to period 1 and 2 of study. Only subjects with negative result were allowed to continue participate in the study. If any subject showed positive result on the examination, this subject was withdrawn from the study. This subject was asked to perform isolation/quarantine for minimum 10 days or another relevant procedure in the accordance with the Indonesian health authority. They should report their condition to appointed healthcare facility. If any subject was COVID-19 confirmed, Investigator reported the event as the Serious Adverse Event to the Sponsor and Ethics Committee. If the number of dropped out subject due to positive result COVID-19 antigen test was highly probable to cause failure of 80% power study, the subject was replaced with the new enrolled subject. Pregnancy test was carried out for female subjects in screening process and on the day of sampling just before the drug administration. Women of childbearing potential were advised to take the necessary precaution to prevent pregnancy and to report to the investigator or Study Physician if they suspected pregnancy. The subjects were required to meet the inclusion and exclusion criteria. The screening data of all subjects were evaluated and subjects with any current or past medical conditions which might significantly affected the study results and assessment were excluded from the study. Investigator or Study Physician decision was needed to decide subject's eligibility if there was an abnormal result, whether it was clinically significant or not. The results of screening were recorded in the Case Report Form |
| Baseline characteristic | |
| Adverse events | There was no adverse events recorded in this study |
| Outcome measures | 1. Cmax
-GMR : 100.27% -90% Confidence interval: 90.80% - 110.74% -CV : 18.10% 2. AUCt -GMR : 98.58% -90% Confidence interval: 92.79% - 104.74% -CV :11.05% |
| 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 available |