Bioequivalence Study of Alprazolam 1 mg Tablets Manufactured by PT Kimia Farma Tbk in Comparison with Xanax® 1 mg Tablets Manufactured by Pfizer Pharmaceutical LLC, Barceloneta, Puerto Rico, Imported by PT Pfizer Indonesia, Jakarta, Indonesia.
| 1. Background | |
|---|---|
| Registration Number | INA-RY6TL0A |
| Date of registry approval | 26-01-2024 |
| Registration Date | 25-01-2024 |
| Secondary identifiers | No |
| Name of issuing authority (for example protocol number, other registries, etc) | |
| Secondary identifier number | |
| Scientific study title | Bioequivalence Study of Alprazolam 1 mg Tablets Manufactured by PT Kimia Farma Tbk in Comparison with Xanax® 1 mg Tablets Manufactured by Pfizer Pharmaceutical LLC, Barceloneta, Puerto Rico, Imported by PT Pfizer Indonesia, Jakarta, Indonesia. |
| Public (popular study title) | Bioequivalence Study of Alprazolam 1 mg Tablets Manufactured by PT Kimia Farma Tbk in Comparison with Xanax® 1 mg Tablets Manufactured by Pfizer Pharmaceutical LLC, Barceloneta, Puerto Rico, Imported by PT Pfizer Indonesia, Jakarta, Indonesia. |
| 2. Sponsor and Funding | |
| Primary Sponsor | PT Kimia Farma Tbk |
| Source(s) of monetary or material support | PT Kimia Farma Tbk |
| 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 | PT. Pharma Metric Labs Gedung Indra Sentral Cempaka Putih Unit R-U Jalan Letjen Suprapto Kav. 60 Central Jakarta, 10520 Indonesia |
| Principal Investigator's email address | alfionita.zalsa@pharmametriclabs.com |
| Public Queries | |
| Contact person name for public queries | Nabila Mudin Sutanto, Pharm |
| 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 | |
| Affiliation for public queries | PT Pharma Metric Labs |
| Email address for public queries | nabila.pmlabs@pharmametricabs.com |
| Phone number for public queries | +62 21 4265310 |
| Scientific Queries | |
| Name of Contact for scientific queries | Nabila Mudin Sutanto, 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 |
| City | Jakarta |
| Country | Indonesia |
| ZIP | |
| Affiliation of scientific queries contact | PT. Pharma Metric Labs Gedung Indra Sentral Cempaka Putih Unit R-U Jalan Letjen Suprapto Kav. 60 Central Jakarta, 10520 |
| Email address for scientific queries | nabila.pmlabs@pharmametricabs.com |
| 4. IRB & Regulatory | |
| Ethical Approval number | KET-695/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 | 01-06-2024 |
| 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 Email:ec_fkui@yahoo.com |
| Number of Persetujuan Pelaksanaan Uji Klinik (PPUK)/Persetujuan Protokol Uji BE (PPUB) | RG.01.02.321.06.23.01825/UB |
| 5. Status | |
| Countries of recruitment | Indonesia |
| Study sites in Indonesia | PT. Pharma Metric Labs |
| Recruitment status | Complete |
| Date of first enrollment | 14-07-2024 |
| Targeted Sample size | 00024 - |
| Number of enrolled participants | 24 |
| Date of study completion (last participant, last visit) | 30-07-2023 |
| 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) | Alprazolam 1 mg Tablets Manufactured by PT Kimia Farma Tbk |
| Control intervention (control arm) | Xanax® 1 mg Tablets Manufactured by Pfizer Pharmaceutical LLC, Barceloneta, Puerto Rico, Imported by PT Pfizer Indonesia, Jakarta, Indonesia. |
| Intervention assignment | Crossover |
| 7. Eligibility Criteria | |
| Gender inclusion criteria | Male, Female |
| Minimum age | 18 |
| Maximum age | 55 |
| Inclusion criteria | 1. Subjects had read the subject information and able to give written informed consent for
participation in the study and comply with the study protocol/procedures 2. Subjects healthy male and female 3. Subjects age range from 18 – 55 years 4. Subjects’ body mass index between 18 – 25 kg/m2 5. Subjects had a normal electrocardiogram 6. Subjects had resting vital signs (after 10 – 15 minutes of resting) were within the following rang - Systolic blood pressure: 90 – 129 mmHg - Diastolic blood pressure: 60 – 84 mmHg - Pulse/Heart rate: 60 – 100 beats per minute 7.Subjects had no significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening |
| Exclusion criteria | 1.those who were pregnant and/or nursing condition
2.those with a history of hypersensitivity or contraindication to alprazolam, 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. 3.those with a history or presence of medical condition which might significantly influence the pharmacokinetics of the study drug, e.g. chronic gastrointestinal disease, diarrhea, gastric surgery, renal insufficiency, hepatic dysfunction or cardiovascular disease 4. those with a history or presence of any coagulation disorder or clinically significant hematology abnormalities 5. those who had history or presence of myasthenia gravis 6. those with had history or presence of acute narrow angle glaucoma 7. those who disagreed to use non-hormonal contraceptives methods (condom) before any intercourse with their spouse from screening until 7 days after the last drug administration 8. 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 9. those who had participated in any clinical study within 3 months prior to the study (< 90 days). 10. those who had donated or lost 300 mL (or more) of blood within 3 months prior to the study. 11. those who were smoker 12. those with a history of direct contact with a COVID-19 positive person in the subject’s neighborhood 13. those with a history or present of sore throat, fever (with temperature more than 37°C) or dyspnea with in the last 14 days 14. those who were positive to SARS CoV-2 antigen test 15. those who were positive to HIV, HBsAg, and HCV tests (to be kept confidential). 16. those with a history of drug or alcohol abuse within 12 months prior to screening for this study. 17. 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 | AUC0-t, Cmax |
| Metric/method of measurement | Bioequivalence of the test and reference product formulations is assessed by calculating individual AUCt and Cmax values. The mean ratio (test/reference) of the ln-transformed data and their 90% confidence intervals is analyzed with a parametric method (analysis of variance/ANOVA) using Phoenix Winnonlin software or manual calculation which has been validated to Phoenix Winnonlin software. |
| Timepoint(s) of measurement | prior to study drug administration (0 h/blank) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration. |
| Secondary outcome 1 | |
| Name of secondary outcome 1 (SO1) | Tmax, Half life, AUC0-inf |
| Metric/method of measurement (SO1) | Tmax (non-transformed data) is analyzed with a non-parametric method (Wilcoxon sign-ranks test), while t½ (non-transformed data) is analyzed with a parametric (paired T-test) or non-parametric (Wilcoxon sign-ranks test) method depended whether the data is normally distributed or |
| Timepoint(s) of measurement (SO1) | prior to study drug administration (0 h/blank) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration. |
| 9. Study Results | |
| Brief summary of study results | Alprazolam 1 mg tablets manufactured by PT Kimia Farma Tbk was bioequivalent towards its reference product, Xanax® 1 mg Tablets manufactured by Pfizer Pharmaceutical LLC, Barceloneta, Puerto Rico, imported by PT Pfizer Indonesia, Jakarta, Indonesia. |
| Date of results summaries | 01-09-2023 |
| Participant flow | 50 secreened subjects
24 Eligible Subjects |
| Baseline characteristic | |
| Adverse events | |
| Outcome measures | |
| 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)) | |
| Plan for IPD sharing (what IPD will be shared, when, by what mechanism, with whom, and for what types of analyses) | |
| Other important informations | |