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

NCT ID: NCT02064504

Last Updated: 2017-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-19
• Study Completion Date: 2014-05-20

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sequence 1

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).

Group Type: EXPERIMENTAL

GSK961081

Intervention Type: DRUG

Dry white to off white powder

Fluticasone furoate

Intervention Type: DRUG

Dry white powder

Sequence 2

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

Group Type: EXPERIMENTAL

GSK961081

Intervention Type: DRUG

Dry white to off white powder

Fluticasone furoate

Intervention Type: DRUG

Dry white powder

Sequence 3

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

Group Type: EXPERIMENTAL

GSK961081

Intervention Type: DRUG

Dry white to off white powder

Fluticasone furoate

Intervention Type: DRUG

Dry white powder

Sequence 4

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

Group Type: EXPERIMENTAL

GSK961081

Intervention Type: DRUG

Dry white to off white powder

Fluticasone furoate

Intervention Type: DRUG

Dry white powder

Sequence 5

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

Group Type: EXPERIMENTAL

GSK961081

Intervention Type: DRUG

Dry white to off white powder

Fluticasone furoate

Intervention Type: DRUG

Dry white powder

Sequence 6

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

Group Type: EXPERIMENTAL

GSK961081

Intervention Type: DRUG

Dry white to off white powder

Fluticasone furoate

Intervention Type: DRUG

Dry white powder

Interventions

GSK961081

Dry white to off white powder

Intervention Type: DRUG

Fluticasone furoate

Dry white powder

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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.
• Urinary cotinine/ Breath carbon monoxide (CO) levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening and a pack year history of </=10 pack years.
• A positive pre-study drug/alcohol screen.
• A positive test for Human Immunodeficiency Virus (HIV) antibody.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Lactating females.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Randwick, New South Wales, Australia

Countries

Australia

Study Documents

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

201010

Identifier Type: -

Identifier Source: org_study_id