A Relative Bioavailability Study of Fluticasone Furoate and Levocabastine

NCT01962467 | Completed Phase 1

• 1 other identifier: 200284
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, randomized, 3-way cross-over, and repeat administration study in healthy male and female subjects. The purpose of the study is to determine the relative bioavailability of Fluticasone Furoate (FF) and Levocabastine (LEV), when each is administered alone and as FF/LEV Fixed Dose Combination (FDC).This study consists of Part A (in which 30 subjects including 12 Korean subjects will be enrolled) and Part B (in which 18 subjects will be enrolled). Each part will consist of three treatment periods separated by a minimum washout period of 14 days. In each treatment period, subjects will receive seven daily doses of one of the 3 treatments: FF, LEV or FF/LEV FDC, via an intranasal spray according to one of the 6 possible randomization sequences. The study will use an adaptive design with an interim review following Part A to confirm whether Part B is required.

Conditions

Rhinitis, Allergic, Perennial and Seasonal

Keywords

Allergic rhinitis; healthy volunteers; fluticasone furoate; levocabastine; fixed dose combination; pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Plasma concentrations of FF and LEV

  Concentrations of FF and LEV will be determined in plasma samples

  Day 7 (Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose) and Day 8 (24 hours post-dose) of each treatment period

• Pharmacokinetic (PK) parameters for both FF and LEV

  From the plasma concentration-time data, area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) of FF and LEV were determined

  Day 7 (Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose) and Day 8 (24 hours post-dose) of each treatment period

Secondary Outcomes (2)

• PK parameters for both FF and LEV alone and in combination

  Day 7 (Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose) and Day 8 (24 hours post-dose) of each treatment period

• tmax

  Day 7 (Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose) and Day 8 (24 hours post-dose) of each treatment period

Study Arms (1)

Arm 1

EXPERIMENTAL

Each subject will receive 7 once daily doses of one of the 3 treatments (FF/LEV FDC or FF or LEV) administered as two 50 µL sprays per nostril in the morning, during each of the 3 treatment periods, as per one of the 6 possible randomization sequences. Each treatment period will be separated by a minimum washout period of 14 days

Drug: FF/LEV FDC; Drug: FF; Drug: LEV

Interventions

FF/LEV FDC DRUG

Intranasal aqueous microsuspension containing 25.0 microgram (µg) of FF and 50 µg of LEV as a fixed dose combination. It will be administered as two 50 µL sprays per nostril in the morning in a fasted state

Arm 1

FF DRUG

Intranasal aqueous microsuspension containing 27.5µg of FF. It will be administered as two 50 µL sprays per nostril in the morning in a fasted state

Arm 1

LEV DRUG

Intranasal aqueous microsuspension containing 50 µg of LEV. It will be administered as two 50 µL sprays per nostril in the morning in a fasted state

Arm 1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/Females aged between 18, 20 for Korean subjects, and 65 years of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• Caucasian, defined as having four grandparents who were descendents of European Caucasians, or Korean origin defined as being born in mainland Korea, having four ethnic Korean grandparents, holding a Korean passport or identity papers and being able to speak Korean. Korean subjects should also have lived outside their respective countries for less than 10 years.
• Body weight \>=50 kilogram (kg), \>=45 kg for Korean subjects, and body mass index (BMI) within the range 18 - 30 Kilogram per meter square (kg/m\^2) (inclusive).
• A female subject is eligible to participate if she is of: non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy \[for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records\]; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 milli-international units per milliliter (MIU/mL) and estradiol \<40 picogram/milliliter (pg/mL) (\<147 picomole/liter) is confirmatory\]; child-bearing potential with negative pregnancy test as determined by urine Human Chorionic Gonadotropin (hCG) test at screening or prior to dosing AND agrees to use one of the contraception methods as described for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 8 days post-last dose.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
• Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin \<=1.5 x Upper Limit of Normal (ULN) \[isolated bilirubin \>1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%\].
• Based on single or averaged corrected QT interval (QTc) values of triplicate electrocardiograms (ECGs) obtained over a brief recording period: QT interval corrected for heart rate using Fridericia'sformulas (QTcF) \<450 milliseconds (msec).
• Criteria Based Upon Medical Histories:
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of regular alcohol consumption within 6 months of the study defined as: For Australian (AUST) sites: An average weekly intake of \>21 units for males or \> 14 units for females. In Australia one unit (=standard drink) is equivalent to 10 grams (g) of alcohol: 270 mL of full strength beer (4.8%), 375 mL of mid strength beer (3.5%), 470 mL of light beer (2.7%), 250 mL pre-mix full strength spirit (5%), 100 mL of wine (13.5%) and 30 mL of spirit (40%).
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation.
• Nasal abnormalities likely to affect the outcome of the study, i.e., nasal septal perforation, nasal polyps, other nasal malformations.
• History of frequent nosebleeds.
• Subjects should be non-smokers, which for this study is defined as having smoked \< 10 pack years in their lifetime, and have not smoked in the 6 months prior to the screening visit.
• Criteria Based Upon Diagnostic Assessments
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

Related Links

• Results for study 200284 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Rhinitis; Rhinitis, Allergic

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2013
• First Posted: October 14, 2013
• Study Start: October 11, 2013
• Primary Completion: February 27, 2014
• Study Completion: February 27, 2014
• Last Updated: May 15, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)