Study to Determine the Pharmacokinetics of GSK961081 and Fluticasone Furoate When Administered Alone or in Combination

NCT02064504 | Completed Phase 1

• 1 other identifier: 201010
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

GSK961081 is a novel bifunctional molecule that combines muscarinic antagonism and beta2-agonism in a single molecule and is in development for the treatment of chronic obstructive pulmonary disease (COPD). This is a randomised, open-label, six-way crossover, single dose study. This study evaluates the drug delivery and systemic pharmacokinetics of GSK961081 following concurrent administration of GSK961081 and fluticasone furoate via dry powder inhaler (DPI) in comparison to GSK961081 DISKUS. There will be six treatment periods and 7 days washout period in the study. Subjects will attend the unit in the morning for dosing and will be resident until 12 hours post administration. All subjects will receive six treatments.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Respiratory; GSK961081 (MABA); healthy subjects; pharmacokinetics; GW685698 (fluticasone furoate)

Outcome Measures

Primary Outcomes (1)

• GSK961081 AUC(0-t')

  Blood samples will be collected to estimate the area under the concentration-time curve from zero (pre-dose) to last common time of quantifiable concentration across all treatments for an analyte where t'=common time AUC(0-t') of GSK961081 following concurrent administration of GSK961081 and fluticasone furoate via DPI in comparison to GSK961081 DISKUS

  Pre dose, 5 minutes (min), 15 min, 30 min, 45 min, 1 hour (h), 2 h, 4 h, 6 h, 8 h, 10 h and 12 h for each treatment period

Secondary Outcomes (5)

• Cmax

  Pre dose, 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h and 12 h for each treatment period

• AUC(0-t') and Cmax following single and dual strip administration of GSK961081

  Pre dose, 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h and 12 h for each treatment period

• AUC(0-t') and Cmax following concurrent administration of GSK961081 and fluticasone furoate

  Pre dose, 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h and 12 h for each treatment period

• Fluticasone furoate AUC(0-t') and Cmax

  Pre dose, 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h and 12 h for each treatment period

• Number of participants with Adverse Events

  Up to 12 Weeks

Study Arms (6)

Sequence 1

EXPERIMENTAL

Participants will receive the study treatment in the following order: ABFCED in each period (one per period). Where A=GSK961081 administered from DISKUS, B=GSK961081 Single strip (SS) administered from DPI, C=GSK961081 Dual Strip (DS) administered from DPI with a filled (lactose) second strip (DS configuration), D=GSK961081/fluticasone furoate (GSK961081/FF) administered from DPI (GSK961081 higher dose), E=FF DS administered from DPI with a filled (lactose) second strip (dual strip configuration), F=GSK961081/FF administered from DPI (GSK961081 lower dose).

Drug: GSK961081; Drug: Fluticasone furoate

Sequence 2

EXPERIMENTAL

Participants will receive the study treatment in the following order: BCADFE in each period (one per period)

Drug: GSK961081; Drug: Fluticasone furoate

Sequence 3

EXPERIMENTAL

Participants will receive the study treatment in the following order: CDBEAF in each period (one per period)

Drug: GSK961081; Drug: Fluticasone furoate

Sequence 4

EXPERIMENTAL

Participants will receive the study treatment in the following order: DECFBA in each period (one per period)

Drug: GSK961081; Drug: Fluticasone furoate

Sequence 5

EXPERIMENTAL

Participants will receive the study treatment in the following order: EFDACB in each period (one per period)

Drug: GSK961081; Drug: Fluticasone furoate

Sequence 6

EXPERIMENTAL

Participants will receive the study treatment in the following order: FAEBDC in each period (one per period)

Drug: GSK961081; Drug: Fluticasone furoate

Interventions

GSK961081 DRUG

Dry white to off white powder

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Fluticasone furoate DRUG

Dry white powder

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Eligibility Criteria

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

You may qualify if:

• Male/females aged between 18 and 64 years of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• Body mass index (BMI) within the range 18 to 29.0 kilogram (kg)/meter (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) greater than 40 MlU/mL and estradiol less than 40 picogram (pg)/mL (less than 147 pmol/L) is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use the 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 enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
• Child-bearing potential with negative pregnancy test as determined by serum human chorionic gonadotropin (hCG) test at screening or urine hCG test prior to dosing AND Agrees to use one of the contraception methods 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 for 5 terminal half-lives after the end of the study (i.e. until after the follow-up visit is complete).
• OR has only same-sex partners, when this is her preferred and usual lifestyle.
• 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 less than or equal to 1.5x upper limit of normal (ULN) (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
• Forced Expiratory Volume in 1 second (FEV1) greater than or equal to 85% predicted and a FEV1/ Forced Vital capacity (FVC) ratio greater than or equal to 0.7
• Based on single or averaged QTc values of triplicate Electrocardiograms (ECGs) obtained over a brief recording period:
• QT duration corrected for heart rate by Fridericia's formula (QTcF) less than 450 millisecond.
• 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:
• An average weekly intake of greater than 21 units for males or greater than 14 units for females. In Australia one unit (= standard drink) is equivalent to 10 gram 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 GSK Medical Monitor, contraindicates their participation.
• 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

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
• Results for study 201010 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

batefenterol; fluticasone furoate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: February 13, 2014
• First Posted: February 17, 2014
• Study Start: February 19, 2014
• Primary Completion: May 20, 2014
• Study Completion: May 20, 2014
• Last Updated: May 15, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)