Bioequivalence study Not Applicable
Conditions
Interventions
The following visits will be performed:
1. Screening phase: between Day -28 and Day -2
2. Interventional phase:
Period 1: Day -1 to 3
Wash-out interval of at least 10 days
Period 2: Day -1 to 3
A si
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 to 45 years old, both inclusive 2. Male or non-pregnant, non-lactating female 2.1. Female of childbearing potential must have a negative serum beta human chorionic gonadotropin (ß-HCG) pregnancy test performed within 28 days prior to the first dosing day. They must be using an acceptable form of contraception. 2.2. For females of childbearing potential, acceptable forms of contraception include the following: 2.2.1. Non-hormonal intrauterine device in place for at least 3 months prior to the start of the study and remaining in place during the study period, or 2.2.2. Barrier methods containing or used in conjunction with a spermicidal agent, or 2.2.3. Surgical sterilization or 2.2.4. Practicing sexual abstinence throughout the course of the study 2.3. Females will not be considered of childbearing potential if one of the following is reported and documented on the medical history: 2.3.1. Postmenopausal with spontaneous amenorrhea for at least 1 year, or 2.3.2. Bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months, or 2.3.3. Total hysterectomy and an absence of bleeding for at least 3 months 3. BMI: 18.5 to 30.0 kg/m², both inclusive; BMI value should be rounded off to one significant digit after decimal point (e.g. 30.04 rounds down to 30.0, while 18.45 rounds up to 18.5) 4. Able to communicate effectively with study personnel 5. Willing to provide written informed consent to participate in the study 6. Non-smokers and non-tobacco users (i.e. having no past history of smoking and tobacco consumption for at least 1 year prior to the study) 7. All volunteers must be judged by the principal or sub-investigator or physician as normal and healthy during a pre-study safety assessment performed within 28 days of the first dose of study medication which will include: 7.1. A physical examination (clinical examination) with no clinically significant finding 7.2. Results within normal limits defined site normal range for the following tests: 7.2.1. Hematology: haemoglobin, total RBC count, total WBC count, platelet count, differential leukocyte count: neutrophils, lymphocytes, eosinophils, monocytes, basophils, blood indices: HCT, glucose-6-phosphate dehydrogenase (G6PD) 7.2.2. Biochemistry: BUN, serum creatinine, random glucose, SGPT & SGOT, alkaline phosphatase, uric acid, serum bilirubin, serum total protein: total proteins, albumin, serum electrolytes: serum sodium, serum chloride, serum potassium, serum phosphorous, serum calcium 7.2.3. Urinalysis: colour, quantity, specific gravity, odour, appearance, reaction, albumin, bilirubin, ketone bodies, sugar, urobilinogen and microscopical examination (performed based on clinical judgment) 7.2.4. Immunological tests: HIV-I & II, HBsAg, syphilis (RPR), anti HCV 7.2.5. Serum (ß-HCG) pregnancy test (for females of childbearing potential) 7.2.6. Additional tests and/or examinations (apart from those mentioned in the protocol) may be performed, if necessary, based on the principal investigator's discretion 7.2.7. All results will be assessed against the current laboratory normal ranges at the time of testing and a copy of the normal ranges used will be included in the study documentation
Exclusion criteria
Exclusion criteria: 1. History of allergic responses to primaquine or other related drugs, or any of its formulation ingredients 2. Have significant diseases or clinically significant abnormal findings during screening [medical history, physical examination (clinical examination), laboratory evaluations, ECG, chest X-ray recording, and, for females, gynaecological history 3. Any disease or condition like diabetes, psychosis or others, which might compromise the haemopoietic, gastrointestinal, renal, hepatic, cardiovascular, respiratory, central nervous system or any other body system 4. History or presence of bronchial asthma 5. Use of any hormone replacement therapy within 3 months prior to the first dose of study medication 6. A depot injection or implant of any drug within 3 months prior to the first dose of study medication 7. Use of CYP enzyme inhibitors or inducers within 30 days prior to the first dose of study medication (see http://medicine.iupui.edu/clinpharm/ddis/main-table) 8. History or evidence of drug dependence or of alcoholism or of moderate alcohol use 9. History of difficulty with donating blood or difficulty with the accessibility of veins 10. A positive hepatitis screen (includes subtypes B & C) 11. A positive test result for HIV antibody and/or syphilis (RPR) 12. Volunteers who have received a known investigational drug within seven elimination half-life of the administered drug prior to the first dose of study medication 13. Volunteers who have donated blood or lost blood: 50 ml to 100 ml within 30 days or 101 ml to 200 ml within 60 days or >200 ml within 90 days (excluding volume drawn at screening for this study) prior to the first dose of study medication, whichever is greater 14. History of difficulty in swallowing or of any gastrointestinal disease, which could affect drug absorption 15. Intolerance to venepuncture 16. Any food allergy, intolerance, restriction or special diet that, in the opinion of the principal investigator or sub-investigator, could contraindicate the volunteer’s participation in this study 17. Institutionalized volunteers 18. Use of any prescribed medications within 14 days prior to the first dose of study medication 19. Use of any OTC products, vitamin and herbal products, etc, within 7 days prior to the first dose of study medication 20. Use of grapefruit and grapefruit-containing products within 7 days prior to the first dose of study medication 21. Ingestion of any caffeine or xanthine products (i.e. coffee, tea, chocolate, and caffeine-containing sodas, colas, etc), recreational drugs, alcohol or other alcohol-containing products within 48 hours prior to the first dose of study medication 22. Ingestion of any unusual diet, for whatever reason (e.g. low sodium) for 3 weeks prior to the first dose of study medication 23. Volunteers with glucose-6-phosphate dehydrogenase (G6PD) deficiency 24. Volunteers with a family or personal history of hemolytic anemia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The bioequivalent rate (Cmax) and extent (AUCt) of absorption of primaquine (plasma concentrations evaluated using LCMS/MS assay) after single dose administration of test and reference products, measured using samples collected at pre-dose (0.0 hour) and at 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.333, 2.667, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, 48.0 and 72.0 hours in each period of this cross over study | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The plasma PK profile of primaquine measured after single-dose administration of the test and reference products, measured using using LCMS/MS on samples collected at pre-dose (0.0 hour) and at 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.333, 2.667, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, and 48.0 hours in each period of this cross over study 2. The plasma PK profile of carboxyprimaquine after single-dose administration of the test and reference products (supportive data), measured using LCMS/MS on samples collected at pre-dose (0.0 hour) and at 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.333, 2.667, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, 48.0 and 72.0 hours in each period of this cross over study 3. Safety and tolerability of subjects after single-dose administration of the test and reference products, assessed by measuring the full blood count and routine biochemistry on the first day of each dosing cycle | — |
Countries
India
Contacts
Public ContactBob Taylor
Outcome results
None listed