Pharmacokinetic Profile of Four Formulations of Fluticasone Furoate (FF) Using Unit Dose Dry Powder Inhaler (UD-DPI) Compared With FF ELLIPTA® Presentation

NCT02218723 | Completed Phase 1

• 1 other identifier: 200939
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, five- period, cross-over, randomized, single dose, single centre study in healthy subjects. This is the second clinical study for the UD-DPI. This study will ascertain whether the Pharmacokinetics (PK) systemic exposure \[in terms of area under the plasma concentration-time curve (AUC) and maximum observed plasma concentration (Cmax)\] of FF delivered via the UD-DPI is comparable to the systemic exposure of FF delivered via the ELLIPTA Dry Powder Inhaler (DPI). For this reason four treatment doses consisting of three dose strengths and 2 percentage blends will be assessed when delivered via the UD-DPI. This study is designed to compare the pharmacokinetic profile of various doses and blends of FF administered via UD-DPI and relative to FF administered via ELLIPTA DPI. Subjects will be screened 28 days prior to study initiation. During each treatment period, subjects will be at study site from evening prior to dosing until completion of the 48 hour post-dose PK sample collection on Day 3. Minimum 7 days washout will be between treatments after completion of all five treatments and the follow-up visit will be conducted 7-14 days post last dose. Duration of study is 13 weeks. ELLIPTA is a registered trademark of the GSK group of companies.

Conditions

Asthma

Keywords

healthy volunteer; Asthma; inhaled corticosteroid; UD-DPI; ELLIPTA DPI; Fluticasone furoate

Outcome Measures

Primary Outcomes (1)

• AUC from time zero (pre-dose) to 24 hours (hr) (AUC [0-24hr]) and/ or AUC from time zero extrapolated to infinite time (AUC [0-infinity]) and/ or AUC from time zero to last time of quantifiable concentration (AUC [0-t])

  AUC (0-24h) and/or AUC(0-t) and/or AUC(0- infinity) will be measured at predose, 5 minutes (min), 10 min, 20 min, 30 min and 45 min, 1 hr, 1.5 hr, 2 hr, 3 hr,4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr and 48 hr

  Day 1, Day 2 and Day3 of each period

Secondary Outcomes (5)

• Cmax

  Day 1, Day 2 and Day3 of each period

• Time to Cmax (tmax)

  Day 1, Day 2 and Day3 of each period

• Safety as assessed by adverse events (AE)

  Up to Week 13

• Safety as assessed by 12 Lead Electrocardiogram (ECG) Parameters

  Day 1 in each period

• Safety as assessed by Vital signs

  Day 1, Day 3 in each period

Study Arms (10)

Sequence ABECD

ACTIVE COMPARATOR

Subject will be administered treatment in sequence ABECD. Where, A: a single dose of FF \[100 microgram (mcg) per blister from 0.6% blend\] delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Drug: FF UD-DPI; Drug: FF ELLIPTA DPI

Sequence BCADE

ACTIVE COMPARATOR

Subject will be administered treatment in sequence BCADE. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Drug: FF UD-DPI; Drug: FF ELLIPTA DPI

Sequence CDBEA

ACTIVE COMPARATOR

Subject will be administered treatment in sequence CDBEA. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Drug: FF UD-DPI; Drug: FF ELLIPTA DPI

Sequence DECAB

ACTIVE COMPARATOR

Subject will be administered treatment in sequence DECAB. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Drug: FF UD-DPI; Drug: FF ELLIPTA DPI

Sequence EADBC

ACTIVE COMPARATOR

Subject will be administered treatment in sequence EADBC. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Drug: FF UD-DPI; Drug: FF ELLIPTA DPI

Sequence DCEBA

ACTIVE COMPARATOR

Subject will be administered treatment in sequence DCEBA. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Drug: FF UD-DPI; Drug: FF ELLIPTA DPI

Sequence EDACB

ACTIVE COMPARATOR

Subject will be administered treatment in sequence EDACB. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Drug: FF UD-DPI; Drug: FF ELLIPTA DPI

Sequence AEBDC

ACTIVE COMPARATOR

Subject will be administered treatment in sequence AEBDC. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Drug: FF UD-DPI; Drug: FF ELLIPTA DPI

Sequence BACED

ACTIVE COMPARATOR

Subject will be administered treatment in sequence BACED. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Drug: FF UD-DPI; Drug: FF ELLIPTA DPI

Sequence CBDAE

ACTIVE COMPARATOR

Subject will be administered treatment in sequence CBDAE. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Drug: FF UD-DPI; Drug: FF ELLIPTA DPI

Interventions

FF UD-DPI DRUG

A blister containing a small quantity of powder comprising of a blend of FF (micronised) and excipient(s) will be administered using UD-DPI. It is available in following dosages: 80mcg/Blister (0.8% Blend); 100mcg/Blister (0.8% Blend); 140mcg/Blister (0.8% Blend); 100mcg/Blister (0.6% Blend)

Sequence ABECD; Sequence AEBDC; Sequence BACED; Sequence BCADE; Sequence CBDAE; Sequence CDBEA; Sequence DCEBA; Sequence DECAB; Sequence EADBC; Sequence EDACB

FF ELLIPTA DPI DRUG

A blister strip contained within the ELLIPTA device. Each blister contains a small quantity of powder comprising of a blend of FF and excipient(s) in dose 100mcg/Blister (0.8% Blend)

Sequence ABECD; Sequence AEBDC; Sequence BACED; Sequence BCADE; Sequence CBDAE; Sequence CDBEA; Sequence DCEBA; Sequence DECAB; Sequence EADBC; Sequence EDACB

Eligibility Criteria

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

You may qualify if:

• AGE- Between 18 and 65 years of age inclusive, at the time of signing the informed consent
• TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY
• Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, and laboratory tests.

You may not qualify if:

• WEIGHT-Body Weight \>= 50 kilogram and BMI within the range 19.0 - 34.0 kilogram per square metre (inclusive)
• SEX
• Male,
• Female subject : is eligible to participate if she is not pregnant \[as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at screening or urine hCG prior to dosing\], not lactating, and at least one of the following conditions applies:
• Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy
• Postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
• Reproductive potential and agrees to follow one of the options listed below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until completion of the follow-up visit.
• GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP)
• This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis.
• Contraceptive subdermal implant that meets the SOP effectiveness criteria including a \<1% rate of failure per year, as stated in the product label
• Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a \<1% rate of failure per year, as stated in the product label
• Oral Contraceptive, either combined or progestogen alone
• Injectable progestogen
• Contraceptive vaginal ring
• Percutaneous contraceptive patches

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

GSK Investigational Site

Adelaide, South Australia, 5000, Australia

Location

Related Links

• Results for study 200939 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung 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: August 14, 2014
• First Posted: August 18, 2014
• Study Start: October 28, 2014
• Primary Completion: December 19, 2014
• Study Completion: December 19, 2014
• Last Updated: July 24, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

AU (2)