A Study to Assess the Effects of Fluticasone Furoate and GW642444M Combination in Healthy Subjects and in Subjects With Mild, Moderate or Severe Hepatic Impairment.

NCT01266941 | Completed Phase 1

• 1 other identifier: 111789
• Study Type: interventional
• Target: 35
• Locations: 2 countries
• Sites: 3

Brief Summary

In relation to their severity, hepatic diseases can significantly modify drug absorption and disposition and consequently can interfere with drug efficacy and/or produce toxicity. The purpose of this study will be to aid in deciding whether a dose adjustment is required in subjects with hepatic impairment and in estimating any such adjustments.

Conditions

Asthma

Keywords

pharmacokinetics; hepatic impairment; heart rate; serum potassium; serum cortisol; GW642444M; Fluticasone furoate (GW685698)

Outcome Measures

Primary Outcomes (1)

• Fluticasone furoate and GW642444 pharmacokinetics (AUC(0-t), AUC (0-8), Cmax, tmax) on Day 1 and 7 and AUC(0-24) and t½ on Day 7.

  1 Month

Secondary Outcomes (4)

• Serum cortisol weighted mean over 24 hours on Days -1 and 7.

  1 Month

• Maximum heart rate over time period 0-4 hours on Day 7.

  1 Month

• Minimum serum potassium concentration over time period 0-4 hours on Day 7.

  1 Month

• General safety and tolerability endpoints: adverse events, blood pressure, heart rate, 12-lead ECG, clinical laboratory safety tests.

  1 Month

Study Arms (4)

Mild Hepatic Impairment

EXPERIMENTAL

Mild and moderate hepatic patients will be recruited first, approximately 9 subjects should complete each of these treatment arms.

Drug: Inhaled FF 200mcg/GW642444M 25mcg

Moderate Hepatic Impairment

EXPERIMENTAL

Mild and moderate hepatic patients will be recruited first, approximately 9 subjects should complete each of these treatment arms.

Drug: Inhaled FF 200mcg/GW642444M 25mcg

Matched healthy volunteers

EXPERIMENTAL

Once a moderate subject has been recruited, a healthy control subject should be recruited (matched to the moderate subject on gender, ethnicity, body mass index +/-15%, age +/-5 years). In total there will be 9 matched healthy volunteers 1 for each subject with moderate hepatic impairment.

Drug: Inhaled FF 200mcg/GW642444M 25mcg

Severe Hepatic Impairment

EXPERIMENTAL

Severe subjects will not be enrolled into the study until 9 moderate subjects and their matched control subjects have completed the study and the safety and PK data have been reviewed.

Drug: Inhaled FF 200mcg/GW642444M 25mcg

Interventions

Inhaled FF 200mcg/GW642444M 25mcg DRUG

All subjects are scheduled to receive FF 200mcg/GW642444M 25mcg once daily for 7 days. The dose for subjects with severe hepatic impairment may be adjusted to FF 100mcg/GW642444M 12.5mcg after review of the PK and safety data from the moderate and healthy matched control subjects.

Matched healthy volunteers; Mild Hepatic Impairment; Moderate Hepatic Impairment; Severe Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between 18 and 70 years of age inclusive, at the time of signing the informed consent.
• 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; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) (healthy subjects only) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 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 and agrees to use one of the contraception methods listed in Section 8.1 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 until completion of the follow-up visit.
• BMI within the range 19 - 33 kg/m\^2.
• Able to satisfactorily use the dry powder inhalation inhaler.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Single QTcF \< 450 msec; or QTcF \< 480 msec in subjects with Bundle Branch Block.
• Able to satisfactorily use the dry powder inhaler.
• Healthy subjects:
• AST, ALT, alkaline phosphatase and bilirubin ≤1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or outcome.
• Hepatically Impaired Subjects:
• \- Hepatically impaired.
• To be classified as hepatically impaired, subjects must have:

You may not qualify if:

• Suffered a lower respiratory tract infection in the 4 weeks before the screening visit.
• Taken oral corticosteroids less than 8 weeks before the screening visit.
• Taken inhaled, intranasal or topical steroids less than 4 weeks before the screening visit.
• Have a known sensitivity to corticosteroids and/or long acting beta agonists.
• A positive pre-study drug/alcohol screen.
• A positive test for HIV antibody.
• 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.
• 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.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
• Lactating females.
• The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Hradec Králové, 500 05, Czechia

Location

GSK Investigational Site

Prague, 170 00, Czechia

Location

GSK Investigational Site

Bratislava, 833 05, Slovakia

Location

Related Publications (1)

• Allen A, Davis A, Hardes K, Tombs L, Kempsford R. Influence of renal and hepatic impairment on the pharmacokinetic and pharmacodynamic properties and tolerability of fluticasone furoate and vilanterol in combination. Clin Ther. 2012 Dec;34(12):2316-32. doi: 10.1016/j.clinthera.2012.11.001. Epub 2012 Nov 30.

  PMID: 23200625 BACKGROUND

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 111789 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: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2010
• First Posted: December 24, 2010
• Study Start: October 18, 2010
• Primary Completion: July 15, 2011
• Study Completion: July 15, 2011
• Last Updated: July 21, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

CZ (2); SL (1)