Pooled Analysis FP_SX_250_50

Pooled Analysis of Individual Subjects' Data After Combining the Data From the Bioequivalence Studies Conducted for Fluticasone Propionate 250 mcg and Salmeterol Xinafoate 50 mcg Inhalation Powder/Respirent Pharmaceuticals (Test, T) vs ADVAIR DISKUS® 250/50 mcg Inhalation Powder/GSK (Reference, R)

A pooled analysis of three bioequivalence studies conducted for Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg inhalation powder/Respirent Pharmaceuticals (Test, T) vs ADVAIR DISKUS® 250/50 mcg inhalation powder/GSK (Reference, R) were conduted.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Test; Drug: Reference

Detailed Description

Data from three Bioequivalence studies with study codes: BECRO/RESP/BREATH-BE250-PIVOTAL (BE250-PIVOTAL), BECRO/RESP/BREATH-BE250-PILOT (BE250-PILOT) and BECRO/RESP/BREATH-PK250 (PK250) were included.

A pooled analysis of all three studies was conducted, including all eighty-two (82) subjects of the three studies. Then, a pooled analysis of the BE250-PIVOTAL and the respective Pilot study (BE250-PILOT) was also conducted since these two studies used products of the same batch, including forty-eight (48) subjects.

• Study Type: Observational
• Enrollment (Actual): 82

Contacts and Locations

Study Locations

• Greece
  • Thessaly
    • Larissa, Thessaly, Greece, 41100
      • BECRO Clinical Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Eighty-two (82) subjects randomised in the studies BE250-PIVOTAL, BE250-PILOT and PK250 were included

Description

Inclusion Criteria:

• Healthy volunteers of both genders, aged ≥18 and ≤60 years.
• Subjects with Body Mass Index (ΒΜΙ) ≥18.5 and <30.0 kg/m2.
• 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.
• 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].
• Subjects that are non-smokers.
• 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.
• Subjects able to use the inhalers according to given instructions, as judged by the Investigator or study nurse.

Exclusion Criteria:

• 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
• Clinically significant illness or surgery within four weeks prior to dosing.
• 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.
• Clinically significant history or presence of chronic bronchitis, emphysema,asthma or any other lung disease.
• History or presence of pulmonary tuberculosis.
• Viral or bacterial, upper or lower respiratory tract infection or sinus or middle ear infection within 4 weeks prior to the screening visit.
• History or presence of significant cardiovascular, endocrinal, neurologic, immunological, psychiatric or metabolic disease.
• History of significant alcohol or drug abuse within one year prior to the screening visit.
• 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].
• Inability to abstain from alcohol for the duration of study period.
• Presence of disease markers for Hepatitis B, Hepatitis C or HIV at screening.
• Positive results for drugs of abuse (barbiturates, marijuana, opioids, benzodiazepines and methadone) in saliva before each administration.
• Positive alcohol breath test before each administration.
• 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 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)
• 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.
• Use of oral or parenteral corticosteroids in the previous four 4 weeks
• Eye disorders especially Glaucoma (or a family history of glaucoma)
• 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.
• Vaccination for prophylaxis from seasonal flu or any other vaccination within seven days prior to administration
• 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.
• A depot injection or an implant of any drug (except hormonal contraceptives) within 3 months prior to treatment administration.
• Donation of plasma (500 ml) within 7 days prior to treatment administration.
• 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.
• Participation in another clinical trial simultaneously.
• Subjects receiving special diet or having intolerance in any of the provided study meals or refusing to eat the study meals
• Application of tattoo or body piercing within 30 days prior to treatment administration.
• Non-tolerance to venipuncture.
• Breastfeeding women.
• Positive pregnancy test at screening
• Females of reproductive age that had sexual intercourse with a nonsterile 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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Test Product; Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg inhalation powder/Respirent Pharmaceuticals	Drug: Test; 2 inhalations of Test and Reference product in each study period; Other Names: Fluticasone propionate 250 mcg and salmeterol xinafoate 50 mcg/Respirent Pharmaceuticals
Reference Product; ADVAIR DISKUS® 250/50 mcg inhalation powder/GSK	Drug: Reference; 2 inhalations of Test and Reference product in each study period; Other Names: ADVAIR DISKUS 250/50

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum plasma concentration, it is read directly from the raw data	up to 36 hours post-administration
AUC(0-t)	Area under the plasma concentration curve from time 0 to the last measured	up to 36 hours post-administration

Collaborators and Investigators

• Sponsor: Respirent Pharmaceuticals Co Ltd.
• Collaborators: Becro Ltd.
• Investigators: Principal Investigator: Elias Zintzaras, Professor, Becro Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 2, 2019
• Primary Completion (ACTUAL): December 31, 2020
• Study Completion (ACTUAL): December 31, 2020

Study Registration Dates

• First Submitted: March 5, 2021
• First Submitted That Met QC Criteria: March 5, 2021
• First Posted (ACTUAL): March 10, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 10, 2021
• Last Update Submitted That Met QC Criteria: March 5, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: bioequivalence; fluticasone propionate; ADVAIR; salmeterol xinafoate; pooled analysis
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Sympathomimetics; Fluticasone; Xhance; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination
• Other Study ID Numbers: 2021-03-010-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes