GSK961081 Alone and With Fluticasone Furoate (FF), Phase 1 (Ph1), Single Dose Regimen (SD), Repeat Dose Regimen (RD), Pharmacokinetic (PK) Study in Healthy Volunteer (HV)

NCT02666287 | Completed Phase 1

• 1 other identifier: 201958
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Batefenterol (BAT) 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). FF is a corticosteroid approved as the inhaled corticosteroid (ICS) component of a combination product, with vilanterol (VI), a long-acting beta2-agonist for COPD. In the current study FF will be investigated as an inhaled product in combination with BAT, for treatment of COPD. This study is an open-label, six-way crossover, single and repeat dose study to evaluate the systemic pharmacokinetics, safety and tolerability of FF and BAT when administered via the ELLIPTA™ alone, in combination, or concurrently at 3 times the clinical dose, following a single dose, and at the proposed clinical dose, following repeat doses. This study will consist of screening period, 6 treatment periods, and a follow-up visit. Each subject will have 3 periods in which they receive a single dose treatment regimen (3 inhalations on Day 1 of each single dose study period) and 3 periods in which they receive a single dose treatment regimen followed by a 7-day, once-daily, repeated dose. On Day 1 of those periods, subjects will receive their single dose as 3 inhalations. On Days 2-8, subjects will receive 1 inhalation per day for the repeated dose regimen. There will be a minimum of 7-day washout between each treatment periods. All subjects will receive 9 treatments and follow-up procedures will be done 7 14 days after the last dose. Forty eight healthy subjects will be enrolled into the study, such that approximately 40 subjects complete dosing and PK assessments. The total duration of participation for each subject in this study will be up to 15 weeks. ELLIPTA is a registered trademark of the GlaxoSmithKline \[GSK\] group of companies.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Fluticasone furoate; Chronic obstructive pulmonary disease; Batefenterol; Dry Powder Inhaler; Respiratory; Pharmacokinetics; Ellipta; Healthy Subjects

Outcome Measures

Primary Outcomes (2)

• Area under the plasma concentration-time curve (AUC) of FF in plasma on Day 7 of repeat dosing

  The following PK parameter will be measured: AUC

  Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dosing on Day 7 of each repeat dose regimen

• Maximum observed plasma concentration (Cmax) of FF in plasma on Day 7 of repeat dosing

  The following PK parameter will be measured: Cmax

  Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dosing on Day 7 of each repeat dose regimen

Secondary Outcomes (15)

• AUC of BAT in plasma on Day 7 of repeat dosing

  Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dosing on Day 7 of each repeat dose regimen

• Cmax of BAT in plasma on Day 7 of repeat dosing

  Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dosing on Day 7 of each repeat dose regimen

• AUC of FF in plasma on Day 1 of study period

  Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dosing on Day 1 of each treatment period

• Cmax of FF in plasma on Day 1 of study period

  Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dosing on Day 1 of each treatment period

• AUC of BAT in plasma on Day 1 of study period

  Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dosing on Day 1 of each treatment period

Study Arms (6)

Sequence 1

EXPERIMENTAL

Each subject will receive all the 9 treatment regimens in the following order: A,G/B/F/C,H/E/D,I with a washout period of 7 days between each treatment period administered via the ELLIPTA inhaler. Where Treatment A= BAT/FF 900/300 microgram (mcg) (3 inhalations of 300/100 mcg). Treatment B= BAT 900 mcg (3 inhalations of 300 mcg) concurrently with FF (lactose) 300 mcg (3 inhalations of 100 mcg) from separate inhalers. Treatment C= BAT 900 mcg (3 inhalations of 300 mcg). Treatment D= FF (lactose) 300 mcg (3 inhalations of 100 mcg). Treatment E= FF (magnesium stearate \[MgSt\]) 300 mcg (3 inhalations of 100 mcg). Treatment F= FF/VI 300/75 mcg (3 inhalations of 100 mcg/25 mcg). Treatment G= 7-day repeat doses: BAT/FF 300/100 mcg (1 inhalation). Treatment H= 7-day repeat doses: BAT 300 mcg (1 inhalation). Treatment I= 7-day repeat doses: FF (lactose) 100 mcg (1 inhalation).

Drug: BAT/FF; Drug: BAT; Drug: FF; Drug: FF (MgSt); Drug: FF/Vilanterol

Sequence 2

EXPERIMENTAL

Each subject will receive all the 9 treatment regimens in the following order: B/C,H/A,G/D,I/F/E with a washout period of 7 days between each treatment period.

Drug: BAT/FF; Drug: BAT; Drug: FF; Drug: FF (MgSt); Drug: FF/Vilanterol

Sequence 3

EXPERIMENTAL

Each subject will receive all the 9 treatment regimens in the following order: C,H/D,I/B/E/A,G/F with a washout period of 7 days between each treatment period.

Drug: BAT/FF; Drug: BAT; Drug: FF; Drug: FF (MgSt); Drug: FF/Vilanterol

Sequence 4

EXPERIMENTAL

Each subject will receive all the 9 treatment regimens in the following order: D,I/E/C,H/F/B/A,G with a washout period of 7 days between each treatment period.

Drug: BAT/FF; Drug: BAT; Drug: FF; Drug: FF (MgSt); Drug: FF/Vilanterol

Sequence 5

EXPERIMENTAL

Each subject will receive all the 9 treatment regimens in the following order: E/F/D,I/A,G/C,H/B with a washout period of 7 days between each treatment period.

Drug: BAT/FF; Drug: BAT; Drug: FF; Drug: FF (MgSt); Drug: FF/Vilanterol

Sequence 6

EXPERIMENTAL

Each subject will receive all the 9 treatment regimens in the following order: F/A,G/E/B/D,I/C,H with a washout period of 7 days between each treatment period.

Drug: BAT/FF; Drug: BAT; Drug: FF; Drug: FF (MgSt); Drug: FF/Vilanterol

Interventions

BAT/FF DRUG

BAT/FF is available in DPI form and will be administered via the ELLIPTA inhaler. Each first strip contains 300 mcg per blister of BAT blended with lactose and its physical appearance is dry white powder. Second strip contains 100 mcg per blister of FF blended with lactose and its physical appearance is dry white powder.

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

BAT DRUG

BAT is available in DPI form and will be administered via the ELLIPTA inhaler. Each first strip contains 300 mcg per blister of BAT blended with lactose appear as dry white powder. Second strip contains lactose which appear as a dry white powder.

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

FF DRUG

FF is available in DPI form and will be administered via the ELLIPTA inhaler. Each first strip contains 100 mcg per blister of FF blended with lactose appear as dry white powder and second strip contains lactose which appear as dry white powder.

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

FF (MgSt) DRUG

FF magnesium stearate is available in DPI form and will be administered via the ELLIPTA inhaler. Each first strip contains 100 mcg per blister of FF blended with lactose appear as dry white powder and second strip contains lactose with magnesium stearate which appear as dry white powder.

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

FF/Vilanterol DRUG

FF/Vilanterol is available in DPI form and will be administered via the ELLIPTA inhaler. Each first strip contains 25 mcg per blister of vilanterol blended with lactose and magnesium stearate appear as dry white powder and second strip contains 100 mcg per blister of FF blended with lactose which appear as 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:

• 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 18.5-30.0 kilogram per meter square (kg/m\^2) inclusive.
• Male or female:
• Males: Male subjects with female partners of child bearing potential must use a condom from the time of first dose of study medication until follow-up, or have had a vasectomy with documentation of azoospermia.
• Females: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin \[hCG\] test), 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.
• Post-menopausal defined as 12 months of spontaneous amenorrhea, with simultaneous follicle stimulating hormone (FSH) and oestradiol 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 in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) during the trial, and until follow-up. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form as described in this protocol.
• Alanine aminotransferase (ALT) and bilirubin \>1.5x upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Mean QTC \> 450 millisecond (msec). NOTES: The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine read or manually over-read.
• The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial.
• For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used as specified in the reporting and analysis plan (RAP).
• Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or 12-lead ECG.
• Pre-existing condition(s) interfering with normal gastrointestinal (GI) anatomy or motility, including constipation, malabsorption or other GI dysfunction which may interfere with the absorption, distribution, metabolism or elimination of the study drug. Subjects with a history of cholecystectomy must be excluded.
• At screening, a supine blood pressure (BP) that is persistently higher (the mean of triplicate measurements taken at least 2 min apart) than 140/90 millimetres of mercury (mmHg).

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Hammersmith Medicines Research: collaborator

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

Related Publications (1)

• Ambery C, Young G, Fuller T, Georgiou A, Ramsay D, Puri A, Daley-Yates P. Open-Label, Crossover Study to Determine the Pharmacokinetics of Fluticasone Furoate and Batefenterol When Administered Alone, in Combination, or Concurrently. Clin Pharmacol Drug Dev. 2019 Feb;8(2):188-197. doi: 10.1002/cpdd.603. Epub 2018 Aug 2.

  PMID: 30070770 DERIVED

Related Links

• Results for study 201958 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2016
• First Posted: January 28, 2016
• Study Start: January 27, 2016
• Primary Completion: June 3, 2016
• Study Completion: June 3, 2016
• Last Updated: May 15, 2017

Record last verified: 2017-05

Locations

GB (1)