A Pilot Bioequivalence Study Between Fluticasone Propionate 500 mcg and Salmeterol Xinafoate 50 mcg Inhalation Powder/Respirent Pharmaceuticals vs. ADVAIR DISKUS® 500/50 Inhalation Powder/GSK in Healthy Volunteers
A Pilot Bioequivalence Study Between Fluticasone Propionate 500 mcg and Salmeterol Xinafoate 50 mcg Inhalation Powder/Respirent Pharmaceuticals vs. ADVAIR DISKUS® 500/50 Inhalation Powder/GSK in Healthy Volunteers
ioequivalence study between two inhaler products of fixed dose combination of fluticasone
 propionate and salmeterol xinafoate inhalation powder
A bioequivalence study of a single dose of the fixed-dose combination of fluticasone
 propionate and salmeterol xinafoate inhalation powder administered from Fluticasone
 propionate 500 mcg and Salmeterol xinafoate 50 mcg inhalation powder/Respirent
 Pharmaceuticals (test-Τ) as 2 inhalations and ADVAIR DISKUS® 500/50 mcg inhalation powder/GSK
 (reference-R) in healthy volunteers under fasting conditions. The study will be one-center
 crossover, randomized, 2-period, 2-sequence (RT and TR), single dose, laboratory-blinded.
Inclusion Criteria:

 1. Healthy volunteers of both genders, aged ≥18 and ≤60 years.

 2. Subjects with Body Mass Index (ΒΜΙ) ≥18.5 and <30.0 kg/m2.

 3. Healthy volunteers are declared healthy based on medical history, physical
 examination, ECG, pulmonary function test (a forced expiratory volume in 1 second
 (FEV1) ≥80% of the predicted normal value), and clinical laboratory values within the
 laboratory stated normal range; if not within this range, they must be without any
 clinical significance according to the Investigator.

 4. Females who participate in the study are either at reproductive age i.e.pre-menopausal
 or unable to gestate [i.e. post-menopausal (absence of menses for 12 months prior to
 drug administration), hysterectomy, bilateral oophorectomy, tubal ligation at least 6
 months prior to drug administration].

 5. Subjects that are non-smokers.

 6. Subjects that, in the opinion of the principal investigator/medical officer, are able
 to communicate and comply with the study procedures and protocol restrictions as
 evidenced by the Informed Consent Form (ICF) duly read, signed and dated by the
 subject prior to study initiation.

 7. Subjects able to use the inhalers according to given instructions, as judged by the
 Investigator or study nurse.

 Exclusion Criteria:

 1. Hypersensitivity to the active substance(s) or to the excipient (lactose which
 contains small amounts of milk protein may cause allergic reactions) or related class
 (any sympathomimetic drug or any inhaled, intranasal, or systemic corticosteroid
 therapy) of the medicinal product

 2. Clinically significant illness or surgery within four weeks prior to dosing.

 3. Clinically significant ECG abnormalities or vital sign abnormalities (seated systolic
 blood pressure <90 or >140 mmHg, seated diastolic blood pressure <50 or >90 mmHg or
 heart rate less than 50 or over 100 bpm) at screening.

 4. Clinically significant history or presence of chronic bronchitis, emphysema,asthma or
 any other lung disease.

 5. History or presence of pulmonary tuberculosis.

 6. Viral or bacterial, upper or lower respiratory tract infection or sinus or middle ear
 infection within 4 weeks prior to the screening visit.

 7. History or presence of significant cardiovascular, endocrinal, neurologic,
 immunological, psychiatric or metabolic disease.

 8. History of significant alcohol or drug abuse within one year prior to the screening
 visit.

 9. Regular use of alcohol within six months prior to screening visit (more than 14
 alcohol units per week) [1Unit =150 ml of wine, 360 ml of beer, or 45 ml of 40%
 alcohol].

 10. Inability to abstain from alcohol for the duration of study period.

 11. Presence of disease markers for Hepatitis B, Hepatitis C or HIV at screening.

 12. Positive results for drugs of abuse (barbiturates, marijuana, opioids, benzodiazepines
 and methadone) in saliva before each administration.

 13. Positive alcohol breath test before each administration.

 14. Use of soft drugs (such as marijuana) within three months prior to screening or hard
 drugs such as crack, cocaine or heroin within one year prior to screening visit

 15. Intake of any drugs known to induce or inhibit hepatic drug metabolism (examples of
 inducers are barbiturates, carbamazepine, phenytoin, glucocorticoids,
 rifampin/rifabutin; examples of inhibitors are, erythromycin, ketoconazole, indinavir,
 cobicistat-containing products) within one month prior to administration of the study
 medication. Under these circumstances, subject inclusion will be judged by the
 principal investigator.

 16. History of peptic ulcer, other gastrointestinal disorders (e.g. chronic diarrhoea,
 irritable bowel syndrome) or unresolved gastrointestinal symptoms (e.g. diarrhea,
 vomiting) or significant hepatic, renal or other condition that is known to interfere
 with the absorption, distribution, metabolism or excretion of the drug.

 17. Use of oral or parenteral corticosteroids in the previous four 4 weeks

 18. Eye disorders especially Glaucoma (or a family history of glaucoma)

 19. Use of prescription medication (within 14 days prior to the first administration of
 study medication) or over-the-counter (OTC) products (including food supplements
 vitamins and herbal supplements) within one week (7 days) prior to the first
 administration of study medication, except for topical products without systematic
 absorption. Contraceptives are allowed.

 20. Vaccination for prophylaxis from seasonal flu or any other vaccination within seven
 days prior to administration

 21. History of allergy to any food, intolerance or special diet, that in the opinion of
 the medical sub-investigator could contraindicate the subject's participation in the
 study.

 22. A depot injection or an implant of any drug (except hormonal contraceptives) within 3
 months prior to treatment administration.

 23. Donation of plasma (500 ml) within 7 days prior to treatment administration.

 24. Donation of whole blood or loss of whole blood ≥ 500 ml prior to administration of the
 study medication within 30 days prior to treatment administration.

 25. Participation in another clinical trial simultaneously.

 26. Subjects receiving special diet or having intolerance in any of the provided study
 meals or refusing to eat the study meals

 27. Application of tattoo or body piercing within 30 days prior to treatment
 administration.

 28. Non-tolerance to venipuncture.

 29. Breastfeeding women.

 30. Positive pregnancy test at screening

 31. Females of reproductive age that had sexual intercourse with a non-sterile male
 partner without protection within 14 days prior to drug administration

 Reliable contraception methods are considered the following:

 -  combined (estrogen and progestogen containing) hormonal contraception associated with
 inhibition of ovulation: oral, intravaginal or transdermal

 -  progestogen-only hormonal contraception associated with inhibition of ovulation oral,
 implanable or injectable

 -  intrauterine device (IUD)

 -  intrauterine hormone-releasing system (IUS)

 -  bilateral tubal occlusion

 -  vasectomised partner

 -  sexual abstinence