A Bioequivalence Study Between Fluticasone Propionate 250 mcg and Salmeterol Xinafoate 50 mcg Inhalation Powder/Respirent Pharmaceuticals vs. ADVAIR DISKUS® 250/50 Inhalation Powder/GSK in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT03820180
• Recruitment Status: Completed
• First Posted: January 29, 2019
• Last Update Posted: March 27, 2019
• Sponsor: Respirent Pharmaceuticals Co Ltd.
• Collaborator: BECRO Ltd.
• Information provided by (Responsible Party): Respirent Pharmaceuticals Co Ltd.

Study Description

Brief Summary:

Bioequivalence study between two inhaler products of fixed dose combination of fluticasone propionate and salmeterol xinafoate inhalation powder

Condition or disease	Intervention/treatment	Phase
Bioequivalence	Drug: Test Product; Drug: Reference Product	Phase 1

Detailed Description:

A bioequivalence study of a single dose of the fixed-dose combination of fluticasone propionate and salmeterol xinafoate inhalation powder administered from Fluticasone propionate 250 mcg and Salmeterol xinafoate 50 mcg inhalation powder/Respirent Pharmaceuticals (test-Τ) as 2 inhalations and ADVAIR DISKUS® 250/50 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: One-center crossover, randomized, 2-period, 2-sequence (RT and TR), single dose, laboratory-blinded study
• Masking: Single (Outcomes Assessor)
• Masking Description: laboratory-blinded
• Primary Purpose: Other
• Official Title: A Randomized, Single-dose, Open Label, Two-treatment, Two-sequence, Two-period, Crossover Study Under Fasting Conditions to Examine the Bioequivalence Between Fluticasone Propionate 250 mcg and Salmeterol Xinafoate 50 mcg Inhalation Powder/Respirent Pharmaceuticals vs. ADVAIR DISKUS® 250/50 Inhalation Powder/GSK in Healthy Volunteers
• Actual Study Start Date: January 23, 2019
• Actual Primary Completion Date: February 12, 2019
• Actual Study Completion Date: February 19, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Test Product; Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg/Respirent Pharmaceuticals	Drug: Test Product; 2 inhalations of Test and Reference product in each study period; Other Name: Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg/Respirent Pharmaceuticals
Active Comparator: Reference Product; ADVAIR DISKUS® 250/50	Drug: Reference Product; 2 inhalations of Test and Reference product in each study period; Other Name: ADVAIR DISKUS 250/50

Outcome Measures

Primary Outcome Measures :

1. AUC0-t [ Time Frame: up to 36 hours post-administration ]
   Area under the plasma concentration curve from time 0 to the last measured (AUC0-t)
2. Cmax [ Time Frame: up to 36 hours post-administration ]
   Maximum plasma concentration, it is read directly from the raw data

Secondary Outcome Measures :

1. AUC0-∞ [ Time Frame: up to 36 hours post-administration ]
   Area under the plasma concentration-time curve extrapolated to infinity
2. Tmax [ Time Frame: up to 36 hours post-administration ]
   Time until Cmax is reached, it is read directly from the observed concentrations
3. t1/2 [ Time Frame: up to 36 hours post-administration ]
   Plasma concentration halflife, it is calculated from the ratio 0.693/λZ.
4. λz [ Time Frame: up to 36 hours post-administration ]
   Terminal elimination rate constant, calculated from the slope of the final phase of the ln-concentration curve versus time with regression analysis
5. Residual area [ Time Frame: up to 36 hours post-administration ]
   [AUC(0-∞)-AUC(0-t)]/AUC(0-∞)]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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) [1 Unit =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 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 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 or transdermal
• progestogen-only hormonal contraception associated with inhibition of ovulation oral or injectable
• bilateral tubal occlusion
• vasectomised partner
• sexual abstinence

Contacts and Locations

Locations

Greece

BECRO Clinical Facility

Larissa, Thessaly, Greece, 41100

Sponsors and Collaborators

Respirent Pharmaceuticals Co Ltd.

BECRO Ltd.

Investigators

• Principal Investigator: Ioannis Stefanidis, Professor; University of Thessaly Department of Medicine

More Information

• Responsible Party: Respirent Pharmaceuticals Co Ltd.
• ClinicalTrials.gov Identifier: NCT03820180
• Other Study ID Numbers: BECRO/RESP/BREATH-PK250
• First Posted: January 29, 2019
• Last Update Posted: March 27, 2019
• Last Verified: January 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Respirent Pharmaceuticals Co Ltd.:

bioequivalence; fluticasone propionate; salmeterol xinafoate; ADVAIR

Additional relevant MeSH terms:

Respiratory Aspiration; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Fluticasone; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination; Anti-Inflammatory Agents; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Dermatologic Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Sympathomimetics