BIOEQUIVALENCE STUDY OF PRAMIPEXOLE ER 0.375 MG EXTENDED-RELEASE TABLETS MANUFACTURED BY PT SOHO INDUSTRI PHARMASI IN COMPARISON WITH SIFROL® ER 0.375 MG EXTENDED-RELEASE TABLETS MANUFACTURED BY ROTTENDORF PHARMA GMBH, FEDERAL REPUBLIC OF GERMANY, IMPORTED BY PT BOEHRINGER INGELHEIM INDONESIA
| 1. Background | |
|---|---|
| Registration Number | INA-OYH2ERW |
| 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 | 786/STD/PML/2023 |
| Scientific study title | BIOEQUIVALENCE STUDY OF PRAMIPEXOLE ER 0.375 MG EXTENDED-RELEASE TABLETS MANUFACTURED BY PT SOHO INDUSTRI PHARMASI IN COMPARISON WITH SIFROL® ER 0.375 MG EXTENDED-RELEASE TABLETS MANUFACTURED BY ROTTENDORF PHARMA GMBH, FEDERAL REPUBLIC OF GERMANY, IMPORTED BY PT BOEHRINGER INGELHEIM INDONESIA |
| Public (popular study title) | BIOEQUIVALENCE STUDY OF PRAMIPEXOLE ER 0.375 MG EXTENDED-RELEASE TABLETS MANUFACTURED BY PT SOHO INDUSTRI PHARMASI IN COMPARISON WITH SIFROL® ER 0.375 MG EXTENDED-RELEASE TABLETS MANUFACTURED BY ROTTENDORF PHARMA GMBH, FEDERAL REPUBLIC OF GERMANY, IMPORTED BY PT BOEHRINGER INGELHEIM INDONESIA |
| 2. Sponsor and Funding | |
| Primary Sponsor | PT. Soho Industri Pharmasi |
| Source(s) of monetary or material support | PT. Soho Industri Pharmasi |
| Other partners | PT. Pharma Metric Labs |
| 3. Contact details | |
| Principal Investigator | |
| Principal investigator | FD Suyatna, MD, PhD, SpFK |
| City | Jakarta |
| Country | Indonesia |
| Principal investigator's affiliation | Medical Faculty, University of Indonesia |
| Principal Investigator's email address | fransdsuyatna@yahoo.com |
| Public Queries | |
| Contact person name for public queries | Virrisya |
| Address for public queries | PT. Soho Industri Pharmasi Jl. Pulogadung No.6, RW.3, Rw. Terate, Kec. Cakung, Kota Jakarta Timur, Daerah Khusus Ibukota Jakarta 13920 |
| City | Jakarta |
| Country | Indonesia |
| ZIP | 13920 |
| Affiliation for public queries | PT. Soho Industri Pharmasi |
| Email address for public queries | virrisya@sohoglobalhealth.com |
| Phone number for public queries | +62 856-9737-5813 |
| Scientific Queries | |
| Name of Contact for scientific queries | Venska Hendriana Wilda, 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 | venska.wilda@pharmametriclabs.com |
| 4. IRB & Regulatory | |
| Ethical Approval number | KET-133/UN2.F1/ETIK/PPM.00.02/2024 |
| Name of Ethics committee | Komite Etik Penelitian Kesehatan Fakultas Kedokteran Universitas Indonesia |
| Date of Ethic approval | 22-01-2024 |
| Contact details of Ethic Committee (phone, email, and office) | Komite Etik Penelitian Kesehatan FKUI-RSUPN Dr. Cipto Mangunkusumo Jalan Salemba Raya No.6 Jakarta, 10430 Telp : (021) 3157008 https://komite-etik.fk.ui.ac.id/ |
| Number of Persetujuan Pelaksanaan Uji Klinik (PPUK)/Persetujuan Protokol Uji BE (PPUB) | RG.01.02.321.05.24.02645/UB |
| 5. Status | |
| Countries of recruitment | Indonesia |
| Study sites in Indonesia | PT. Pharma Metric Labs |
| Recruitment status | Complete |
| Date of first enrollment | 06-06-2024 |
| Targeted Sample size | 00020 - |
| Number of enrolled participants | 20 |
| Date of study completion (last participant, last visit) | 22-06-2024 |
| 6. Study Design & Purpose | |
| Primary health condition(s) or problem(s) studied (e.g., depression, breast cancer,medication error) | Healthy human volunteer |
| Purpose of the study | BE Study for product registration |
| 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) | Pramipexole ER 0.375 mg |
| Control intervention (control arm) | Sifrol ER 0.375 mg |
| Intervention assignment | Crossover |
| 7. Eligibility Criteria | |
| Gender inclusion criteria | Male, Female |
| Minimum age | 18 |
| Maximum age | 55 |
| Inclusion criteria | Subjects had read the subject information and were able to give written informed consent for participation in the study and comply with the study protocol/procedures, Subjects healthy male and female, Subjects’ age ranges from 18 – 55 years, Subjects’ body mass index between 18 – 25 kg/m2, Subjects had a normal electrocardiogram, Subjects had resting vital signs (after 10 – 15 minutes of resting) were within the following range: Systolic blood pressure 110 – 129 mmHg; Diastolic blood pressure 70 – 84 mmHg; Pulse/Heart rate 60 – 100 beats per minute, Subjects had no significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening, Subjects had received the complete primary SARS CoV-2 vaccine, Subjects had negative result of SARS CoV-2 antigen test (for those who has not received the first booster vaccine) |
| Exclusion criteria | those who were pregnant and/or nursing women (for women), those with history of contraindication or hypersensitivity to pramipexole, or allied drugs, or other ingredients in the study products, or a history of serious allergic reaction to any drug, 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/intestinal surgery, renal insufficiency, hepatic dysfunction or any cardiovascular disease, those with history or presence of any coagulation disorder or clinically significant hematology abnormalities, those who had history of orthostatic hypotension, those who were disagreed to use non-hormonal contraceptives methods (condom) before any intercourse with their spouse within study period, those who using any medication (prescription or non-prescription drug, food supplement, herbal medicine), particularly the medication known to affect the pharmacokinetics of the study drug, within one week prior to the drug administration day, those who participated in any clinical study within the past 90 days prior to the study, those who donated or losing 300 mL (or more) of blood within 3 months prior to the study, those who had smoking habit with more than 10 cigarettes a day, those who had history of direct contact with a COVID-19 positive person in the subject’s neighborhood within the last 14 days prior to screening, those who had history or present of sore throat, fever (with temperature more than 37°C), cough, cold, anosmia/loss of smell, or dyspnea within the last 14 days, those who had positive result for HIV, HbsAg, and HCV tests (to be kept confidential), those who had history of drug or alcohol abuse within 12 months prior to screening for this study, those who were unlikely to comply with the protocol, e.g. uncooperative attitude, inability to return for follow up visits, poor venous access |
| 8. Study Outcome | |
| Primary Outcome | |
| Name of primary outcome | Cmax, AUCt, and AUCinf |
| Metric/method of measurement | Statistical analysis (analysis of variance/ANOVA) using Phoenix WinNonlin software or manual calculation (Microsoft Excel 2016) which has been validated to Phoenix WinNonlin software |
| Timepoint(s) of measurement | Blood samples were drawn prior to study drug administration (0 h/blank), and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 24, 36, 48 and 72 hours after drug administration. |
| Secondary outcome 1 | |
| Name of secondary outcome 1 (SO1) | Tmax, T1/2 |
| Metric/method of measurement (SO1) | Statistical analysis (analysis of variance/ANOVA) using Phoenix WinNonlin software or manual calculation (Microsoft Excel 2016) which has been validated to Phoenix WinNonlin software |
| Timepoint(s) of measurement (SO1) | Blood samples were drawn prior to study drug administration (0 h/blank), and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 24, 36, 48 and 72 hours after drug administration. |
| 9. Study Results | |
| Brief summary of study results | Results from this bioequivalence study of Pramipexole ER 0.375 mg extended-release tablets (test
product) in comparison with Sifrol® ER 0.375 mg extended-release tablets (reference drug) were as following: 90.00% confidence intervals of geometric means ratio of the two bioavailability parameters of Pramipexole were 86.67% - 105.68% for Cmax and 90.19% - 106.91% for AUCt. These results showed that, Pramipexole ER 0.375 mg extended-release tablets was bioequivalent towards its reference product, Sifrol® ER 0.375 mg extended-release tablets |
| Date of results summaries | 30-07-2024 |
| Participant flow | Informed consent was obtained from each subject before the screening process and the participation must be voluntary. All subjects were informed of possible side effects or adverse events and advised that they were free to withdraw from the study at any stage. The investigator informed all subjects about the details of the study, i.e. the objective and the procedure, as well as the study rules or restrictions to be followed during the study and the possible adverse effects of the drug.
Medical history, physical examination, laboratory tests (routine hematology, blood biochemistry and urinalysis), electrocardiograph, vital sign (blood pressure, pulse rate, respiration rate and body temperature), pregnancy test and HIV, HBsAg, HCV tests were carried out to screen and obtain eligible subjects who met the inclusion and exclusion criteria. All involved subjects should be received the complete primary SARS CoV-2 vaccine and the first booster. SARS CoV-2 antigen test was carried out for subjects who had not received the first booster vaccine. SARS CoV-2 antigen test was performed on the screening day and on 1 day prior to the study day on period 1 and 2. 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. From a total of 20 healthy enrolled subjects, all subjects completed the study and statistically evaluated. |
| Baseline characteristic | |
| Adverse events | Adverse event recorded in this study was nausea |
| Outcome measures | Pramipexole ER 0.375 mg vs Sifrol ER 0.375 mg
1. Cmax: Geometeric means Ration: 95.70% 90% CI of GMR: 86.67-105.68% Intra-subject CV: 18.08% 2. AUCt: Geometeric means Ration: 98.20% 90% CI of GMR: 90.19 - 106.91% Intra-subject CV: 15.51% Pharmacokinetic results of Pramipexole ER 0.375 mg 1. Cmax : 637.72 (258.17) 2. AUCt: 13764.09 (4453.20) 3. AUCinf: 15104.42 (4081.50) 4. Tmax: 8.00 (5.00 - 16.00) 5. T1/2: 20.66 (11.54) Pharmacokinetic Results of Sifrol ER 0.375 mg 1. Cmax : 659.32 (222.92) 2. AUCt: 14062.84 (4581.19) 3. AUCinf: 15689.03 (5215.73) 4. Tmax: 8.00 (5.00 - 14.00) 5. T1/2: 22.96 (21.77) |
| 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 | |