Bioequivalence study in healthy volunteers Not Applicable
Conditions
Interventions
A single dose of test (T) and reference (R) treatments, both combining ramipril 10 mg and furosemide 25 mg, will be administered to healthy male and female volunteers under fasting conditions in two s
Sponsors
Neopharmed Gentili S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent: signed written informed consent before inclusion in the study 2. Sex and Age: males/females, 18 - 55 year old inclusive 3. Body Mass Index: 18.5 - 28 kg/m² inclusive 4. Vital signs: systolic blood pressure 100 - 139 mmHg, diastolic blood pressure 60 - 89 mmHg, heart rate 50-90 bpm, measured after 5 min at rest in the sitting position 5. Body temperature: 35.7 - 37.5° C at screening 6. Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study 7. Contraception and fertility (women): women of child-bearing potential must be using at least one of the following reliable methods of contraception: 7.1. Hormonal oral, implantable, transdermal or injectable contraceptives for at least 2 months before the screening visit 7.2. A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit 7.3. A male sexual partner who agrees to use a male condom with spermicide 7.4. A sterile sexual partner Female participants of non-child-bearing potential or in post-menopausal status for at least one year will be admitted. For all women, pregnancy test result must be negative at screening and Day -1.
Exclusion criteria
Exclusion criteria: 1. Electrocardiogram (12-lead ECG in supine position): clinically significant abnormalities 2. Physical findings: clinically significant abnormal physical findings indicative of physical illness 3. Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness 4. Virology: positive result of serum virology assays 5. Allergy: ascertained or presumptive hypersensitivity to the active principles and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study 6. Hypotension and heart rate: during the screening procedures or history of orthostatic hypotension or syncope/fainting or heart rate 1 drink/day for women and >2 drinks/day for men, defined according to the USDA Dietary Guidelines 2015-2020), caffeine (>5 cups coffee/tea/day) or tobacco abuse (=10 cigarettes/day) 12. Drug test: positive result at the drug test at screening 13. Alcohol test: positive alcohol breath test at Day -1 14. Diet: abnormal diets (3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians 15. Pregnancy (women only): positive or missing pregnancy test at screening or Day -1, pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Bioequivalent rate (Cmax) and extent (AUC0-t) of absorption of ramipril and furosemide calculated from plasma concentrations after single dose administration of T and R treatments (where Cmax = Maximum plasma concentration and AUC0-t = Area under the concentration-time curve from administration to the last observed concentration time t, calculated with the linear trapezoidal method) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The plasma pharmacokinetic profile of ramipril and furosemide in terms of AUC0-t, tmax, t1/2 and Frel calculated from plasma concentrations after single dose administration of T and R treatments (where AUC0-t = Area under the concentration-time curve extrapolated to infinity, calculated, if feasible, as AUC0-t + Ct/?z, where Ct is the last measurable drug concentration and ?z = Terminal elimination rate constant, calculated, if feasible, by log-linear regression using at least 3 points, where tmax = Time to achieve Cmax, where t1/2 = Half-life, calculated, if feasible, as ln2/?z, where Frel = Relative bioavailability, calculated as ratio AUC0-t (test)/ AUC0-t (reference)) 2. Safety and tolerability data of test and reference treatments after single dose administration measured using adverse events, vital signs (blood pressure and heart rate), body weight, ECG, laboratory parameters taken from case report forms | — |
Countries
Switzerland
Contacts
Public ContactLeonardo Rabaglia
Outcome results
None listed