Bioequivalence study of a new capsule containing ramipril 10 mg and bisoprolol fumarate 5 mg (Neopharmed Gentili S.r.l.) versus the simultaneous administration of ramipril 10 mg tablets ( Triatec®, Sanofi-Aventis) and bisoprolol fumarate 5 mg film coated tablets (Congescor®, Daiichi Sankyo) in healthy male and female volunteers under fasting conditions

INTERVENTION: The study protocol foresaw 2 periods separated by a wash‐out interval of at least 14 days between consecutive administrations. The following visits were performed: Screening phase ‐ Screening – visit 1: between Day ‐14 and Day ‐2 ‐ Period 1 – visit 2: Day ‐1 Interventional phase ‐ Period 1 – visit 3: Days 1‐3 ‐ Wash‐out interval of at least 14 days ‐ Period 2 – visit 4: Day ‐1 ‐ Period 2 – visit 5: Days 1‐3 Final phase ‐ Final visit/early termination visit (ETV). In case of early discontinuation, discontinued subjects underwent an early termination visit (ETV) A single dose of the test fixed dose combination or of the reference extemporaneous combination, both corresponding to ramipril 10 mg and bisoprolol fumarate 5 mg, was administered to healthy male and female volunteers under fasting conditions in two study periods according to a randomised 2‐way cross‐over design, with a wash‐out interval of at least 14 days between consecutive administrations. Both test and reference treatments were orally administered in the morning of study Day 1, at 08:00±1h. One hard capsule of fixed dose combination of ramipril 10 mg / bisoprolol fumarate 5 mg (test treatment) or one tablet of Triatec®, 10 mg + one tablet of Congescor®, 5 mg (reference treatment) were swallowed with 150 mL of still mineral water by the subjects. Vital signs were checked and blood samples for PK analysis were collected at specific timepoints. TEST (T): IMP Ramipril 10 mg / Bisoprolol fumarate 5 mg hard capsules (NG8706), Neopharmed Gentili S.r.l., Italy REFERENCE (R) IMP: Triatec®, 10 mg ramipril tablets + Congescor®, 5 mg bisoprolol fumarate film‐coated tablets CONDITION: Not applicable ; Not Applicable PRIMARY OUTCOME: The bioequivalent rate (Cmax) and extent (AUC0‐t) of absorption of ramipril and bisoprolol (plasma concentrations evaluated using an LC/MS‐MS assay) after single dose administration of test and reference products SECONDARY OUTCOME: ; 1. The plasma PK profile (0‐48 hours) of ramipril and bisoprolol after single dose administration of test and reference products; 2. Safety and tolerability of test and reference products after single dose administration; 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 (BMI): 18.5‐28 kg/m2 inclusive 4. Vital signs: systolic blood pressure (SBP) 100‐139 mmHg, diastolic blood pressure (DBP) 60‐89 mmHg, heart rate (HR) 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 (females): females of child‐bearing potential had to be using at least one of the following reliable methods of contraception: 7.1. Hormonal oral,