PROTOCOL AMENDMENT OF BIOEQUIVALENCE STUDY OF 100 MG DOXYCYCLINE HYCLATE (DOXICOR 100) CAPSULES PRODUCED BY PT. GENERO PHARMACEUTICALS IN COMPARISON WITH VIBRAMYCIN® 100 MG CAPSULES MANUFACTURED BY PFIZER LABS, DIVISION OF PFIZER INC, USA
| 1. Background | |
|---|---|
| Registration Number | INA-K6O8786 |
| Date of registry approval | 05-11-2024 |
| Registration Date | 01-11-2024 |
| Secondary identifiers | Yes |
| Name of issuing authority (for example protocol number, other registries, etc) | Protocol Number |
| Secondary identifier number | BE24-23 |
| Scientific study title | PROTOCOL AMENDMENT OF BIOEQUIVALENCE STUDY OF 100 MG DOXYCYCLINE HYCLATE (DOXICOR 100) CAPSULES PRODUCED BY PT. GENERO PHARMACEUTICALS IN COMPARISON WITH VIBRAMYCIN® 100 MG CAPSULES MANUFACTURED BY PFIZER LABS, DIVISION OF PFIZER INC, USA |
| Public (popular study title) | PROTOCOL AMENDMENT OF BIOEQUIVALENCE STUDY OF 100 MG DOXYCYCLINE HYCLATE (DOXICOR 100) CAPSULES PRODUCED BY PT. GENERO PHARMACEUTICALS IN COMPARISON WITH VIBRAMYCIN® 100 MG CAPSULES MANUFACTURED BY PFIZER LABS, DIVISION OF PFIZER INC, USA |
| 2. Sponsor and Funding | |
| Primary Sponsor | PT Genero Pharmaceuticals |
| Source(s) of monetary or material support | Company |
| Other partners | PT. Clinisindo Laboratories |
| 3. Contact details | |
| Principal Investigator | |
| Principal investigator | Prof. Dr. apt. Yahdiana Harahap, MS |
| City | Jakarta |
| Country | Indonesia |
| Principal investigator's affiliation | PT. Clinisindo Laboratories |
| Principal Investigator's email address | info@clinisindo.com |
| Public Queries | |
| Contact person name for public queries | apt. Andrea Elouise, S.Farm |
| Address for public queries | Jl. Ulujami Raya No.12, Pesanggrahan Jakarta Selatan 12250 |
| City | Jakarta |
| Country | Indonesia |
| ZIP | 12160 |
| Affiliation for public queries | PT. Clinisindo Laboratories |
| Email address for public queries | info@clinisindo.com |
| Phone number for public queries | 02173889918 |
| Scientific Queries | |
| Name of Contact for scientific queries | apt. Andrea Elouise, S.Farm |
| Address for scientific queries | Jl. Ulujami Raya No.12, Pesanggrahan Jakarta Selatan 12250 |
| City | Jakarta |
| Country | Indonesia |
| ZIP | 12160 |
| Affiliation of scientific queries contact | Jl. Ulujami Raya No.12, Pesanggrahan Jakarta Selatan 12250 |
| Email address for scientific queries | Andrea.Elouise@clinisindo.com |
| 4. IRB & Regulatory | |
| Ethical Approval number | No. S-155/UN2.F1/ETIK/PPM.00.02/2024 |
| Name of Ethics committee | Komite Etik Penelitian Kesehatan Rsup Nasional Dr. Cipto Mangunkusumo Fakultas Kedokteran Universitas Indonesia |
| Date of Ethic approval | 04-03-2024 |
| Contact details of Ethic Committee (phone, email, and office) | Gedung H Fakultas Kedokteran UI, Jalan Salemba Raya No. 6 Jakarta 10430 PO. Box 1358 Telp: (021) 3157008, website: https://komite-etik.fk.ui.ac.id/ |
| Number of Persetujuan Pelaksanaan Uji Klinik (PPUK)/Persetujuan Protokol Uji BE (PPUB) | RG.01.02.321.03.24.02549/UB |
| 5. Status | |
| Countries of recruitment | Indonesia |
| Study sites in Indonesia | Jl. Ulujami Raya No.12, Pesanggrahan Jakarta Selatan 12250 |
| Recruitment status | Complete |
| Date of first enrollment | 06-06-2024 |
| Targeted Sample size | 00018 - |
| Number of enrolled participants | 18 |
| Date of study completion (last participant, last visit) | 28-06-2024 |
| 6. Study Design & Purpose | |
| Primary health condition(s) or problem(s) studied (e.g., depression, breast cancer,medication error) | The study is conducted in healthy human volunteers |
| Purpose of the study | Bioavailability |
| Study type | Observational |
| Method of allocation | |
| Description of the allocation concealment mechanism and sequence generation | |
| Masking | |
| Study intervention (study arm) | |
| Control intervention (control arm) | |
| Intervention assignment | |
| 7. Eligibility Criteria | |
| Gender inclusion criteria | Male, Female |
| Minimum age | 18 |
| Maximum age | 55 |
| Inclusion criteria | Subjects must satisfied the following criteria to be enrolled in the study: Gave 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 was 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 (was done for female subjects at screening, before period I and before period II of the study), Subject had either received COVID-19 (Coronavirus) vaccine minimum of first booster or negative result for COVID-19 rapid antigen test 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 | Subjects would be excluded if the following reasons existed: Smoker. If necessary, light smoker (≤5 cigarettes/day) could be accepted, Pregnant women or nursing mother, Had history of hepatic, cardiovascular, gastrointestinal or renal disease, Had history or condition of severe/serious skin reactions, Had history or condition of esophageal lesions (esophagitis and ulcerations), Had history or condition of myasthenia gravis, Had history or condition of obstructive esophagic pathology, such as stenosis and achalasia, Had history or condition of autoimmune reactions or disease, Hypersensitivity to doxycycline, tetracycline antibiotics, or similar medication, History of alcohol, drug abuse within 12 months prior to screening for this study, 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, Had symptoms related to COVID-19 (e.g. fever, cough, cold, sore throat, or anosmia) or close contact with COVID-19 patients within fourteen days prior to the start of the study. |
| 8. Study Outcome | |
| Primary Outcome | |
| Name of primary outcome | The primary objective of this study was to establish bioequivalence of 100 mg Doxycycline Hyclate (Doxicor 100) capsules produced by PT. Genero Pharmaceuticals in comparison with Vibramycin® 100 mg capsules manufactured by Pfizer Labs, Division of Pfizer Inc, USA |
| Metric/method of measurement | Descriptive statistics (mean, median, standard deviation, minimum and maximum) were calculated to AUC0-t, AUC0-∞, Cmax, tmax and t1/2. Analysis of variance (ANOVA) were performed using logarithmically transformed AUC0-t, AUC0-∞ and Cmax. Meanwhile, t1/2 parameter was calculated using Paired t-test without logarithmically transformed data. Prior to calculation, t1/2 had been analyzed for normality test of data. tmax was analyzed by nonparametric method (Wilcoxon signed rank test) without logarithmic transformation. |
| Timepoint(s) of measurement | The study consisted of two study periods. Each study period, subjects were fasted at least 8 hours before each drug administration. At ± 07.00 am each subject received single oral dose of one doxycycline hyclate 100 mg capsule, either as test or reference formulations, administered with 220 mL of water. Serial of approximately 5 mL of blood samples were collected in K3EDTA blood collection tube at the following times: pre dose, at 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, and 60 hours after drug administration (18 blood samples) and were repeated after one-week wash-out period. The total maximum volume of blood drawn for every subject was approximately 195 mL during two weeks sampling study period including the screening process (15 mL). Meals and snack were standardized and provided at 4, 8 and 11 hours after dosing similar in both sampling periods |
| 9. Study Results | |
| Brief summary of study results | Based on the results, we concluded that both formulations were bioequivalent. |
| Date of results summaries | 20-09-2024 |
| Participant flow | |
| Baseline characteristic | |
| Adverse events | Most of frequent AEs (n≥2) (%) :
Tachycardia Hypotension Hypertension Prehypertension |
| Outcome measures | Ratio (90% Geometric CI) of Doxicor 100 vs Vibramycin® :
AUC0-t (ng.jam/mL) : 97.03 (93,02–101,21) AUC0-∞(ng.jam/mL) : 96,85 (91,76-102,22) Cmax (ng/mL) : 100,01 (94,00-106,41) |
| 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 | |