Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Fluticasone furoate, Chronic obstructive pulmonary disease, Batefenterol, Dry Powder Inhaler, Respiratory, Pharmacokinetics, Ellipta, Healthy Subjects
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.
Interventions
DRUGBAT/FF
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.
DRUGBAT
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.
DRUGFF
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.
DRUGFF (MgSt)
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.
DRUGFF/Vilanterol
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.
Sponsors
Hammersmith Medicines Research
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Between 18 and 64 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration-time curve (AUC) of FF 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 | The following PK parameter will be measured: AUC |
| Maximum observed plasma concentration (Cmax) of FF 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 | The following PK parameter will be measured: Cmax |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Cmax 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 | — |
| Number of participants with adverse events (AEs) | Up to 15 weeks | An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Safety as assessed by 12-lead Electrocardiogram (ECG) | Up to 15 weeks | A single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and corrected QT (QTc) intervals. |
| 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 | — |
| Safety as assessed by oral temperature measurements | Up to 15 weeks | Oral temperature measurements will be recorded at pre-dose on dosing days |
| Safety as assessed by heart rate measurements | Up to 15 weeks | Three readings of heart rate will be taken at screening and Day -1. Single measurements will be taken at all other timepoints |
| Safety as assessed by respiratory rate measurements | Up to 15 weeks | Respiratory rate measurements will be recorded at pre-dose on dosing days |
| Composite of Haematology parameters as a measure of safety | Up to 15 weeks | The following hematology parameters will be measured: Platelet Count, red blood cell (RBC) count, Hemoglobin, Hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell (WBC) count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils |
| Composite of Clinical Chemistry parameters as a measure of safety | Up to 15 weeks | The following clinical chemistry parameters will be measured: Urea, Creatinine, Glucose (fasting), Uric acid, Potassium, Sodium, Calcium, Chloride, Phosphate, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase, Gamma-glutamyl transferase (GGT), Cholesterol, Triglycerides, Total Bilirubin, Total Protein, Albumin, and Globulin. |
| Composite of Urinalysis parameters as a measure of safety | Up to 15 weeks | The following urinalysis parameters will be measured by dip stick test: protein, blood, ketones, glucose, bilirubin, urobilinogen, leukocyte esterase, specific gravity, nitrites, power of hydrogen (pH). If urine dipstick is abnormal for leukocyte esterase, nitrites, blood or protein, microscopic examination will be performed. |
| Safety as assessed by systolic and diastolic blood pressure measurements | Up to 15 weeks | Three readings of systolic and diastolic pressure will be taken at screening and Day -1. Single measurements will be taken at all other specified timepoints |
| 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 | — |
Countries
United Kingdom
Outcome results
None listed