A Drug Interaction Study With Fluticasone Furoate/GW642444 Inhalation Powder and Ketoconazole

NCT01165125 | Completed Phase 1

• 1 other identifier: 105548
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized two-way crossover study to determine whether concomitant administration of CYP P450 3A4 inhibitor ketoconazole and fluticasone furoate/GW642444M combination significantly increases the systemic effects and exposure to repeat dose fluticasone furoate and/or GW642444 in healthy subjects. Key assessments will include blood potassium, heart rate, blood pressure, QTc, serum cortisol and pharmacokinetic parameters, and safety including vital signs, ECGs, adverse event monitoring and laboratory safety tests, including blood glucose.

Conditions

Asthma

Keywords

pharmacodynamics; drug interaction; ketoconazole; pharmacokinetics; Fluticasone furoate; GW642444

Outcome Measures

Primary Outcomes (2)

• Maximum heart rate (0-4 hours) and minimum blood potassium level (0-4 hours) on the morning of Day 11

  Day 11

• Weighted mean serum cortisol (0-24 hours) on Day 11.

  Day 11

Secondary Outcomes (4)

• Minimum diastolic blood pressure (0-4 hours), maximum systolic blood pressure (0-4 hours) and maximum QTcF (0-4 hours) on the morning of Day 11

  Day 11

• Fluticasone furoate and GW642444 pharmacokinetics (AUC(0-t), AUC(0-24), Cmax, tmax) on Day 5 and 11

  day 11

• Reported adverse events

  2 months

• 12-lead ECG and clinical laboratory data and maximum heart rate (0-4 hours) maximum QTc (0-4 hours) and minimum blood potassium and blood glucose levels (0-4 hours) on the morning of Day 5.

  Day 5

Study Arms (2)

FF/GW642444 and keto

OTHER

Ketoconazole (400mcg) administered on Days 1-11, with co-administration of fFF / GW642444 (200mcg/25mcg) on Days 5-11

Drug: FF / GW642444; Drug: ketoconazole

Ketoconazole Placebo to match & FF/GW642444

OTHER

ketoconazole placebo to match administered on days 1-11. FF/GW642444 (200mcg/25mcg) co-administered on Days 5-11

Drug: FF / GW642444; Drug: ketoconazole (placebo to match)

Interventions

FF / GW642444 DRUG

200mcg/25mcg Novel DPI

FF/GW642444 and keto; Ketoconazole Placebo to match & FF/GW642444

ketoconazole DRUG

400mcg overencapsulated tablets

FF/GW642444 and keto

ketoconazole (placebo to match) DRUG

placebo to match overencapsulated tablets

Ketoconazole Placebo to match & FF/GW642444

Eligibility Criteria

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

You may qualify if:

• Healthy male or female between 18 and 64 years of age 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; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory\]. 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.
• Body mass index within range of 18.5-29.0 kg/m2 inclusive.
• Subjects who are current non-smokers, who have not used any tobacco products in the 12 month period preceding the screening visit, and have a pack history of \</= 5 pack years.
• AST, ALT, alkaline phosphatase and bilirubin \</= 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• No significant abnormality on 12-lead ECG at screening, including the following specific requirements:
• QTcF \< 450 msec
• No clinically significant abnormality on the Holter ECG at screening.
• FEV1 \>/= 85% predicted at screening.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Able to satisfactorily use the dry powder inhaler.

You may not qualify if:

• As a result of medical interview, physical examination or screening investigations, the principal investigator or delegate physician deems the subject unsuitable for the study. Subjects must not have a systolic blood pressure above 145 mmHg or a diastolic pressure above 85 mmHg unless the Investigator confirms that it is satisfactory for their age.
• The subject has any history of breathing problems in adult life (i.e. history of asthmatic symptomatology).
• Pregnant females as determined by positive serum hCG test at screening or by positive serum/urine hCG test 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.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Subjects who have suffered a lower respiratory tract infection within 4 weeks of the screening visit.
• 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.
• Any adverse reaction including immediate or delayed hypersensitivity to any beta-agonist, sympathomimetic drug, or any intranasal, inhaled or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the new powder inhaler (ie lactose or magnesium stearate)
• History of milk protein allergy.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• The subject has taken oral corticosteroids less than 8 weeks before the screening visit.
• The subject has taken inhaled, intranasal or topical steroids less than 4 weeks before the screening visit.
• History of alcohol/drug abuse or dependence within 12 months of the study. Abuse of alcohol defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (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: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

Related Publications (1)

• Kempsford R, Allen A, Bal J, Rubin D, Tombs L. The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of inhaled fluticasone furoate and vilanterol trifenatate in healthy subjects. Br J Clin Pharmacol. 2013 Jun;75(6):1478-87. doi: 10.1111/bcp.12019.

  PMID: 23116485 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 105548 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Asthma

Interventions

Ketoconazole

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: July 19, 2010
• Study Start: July 1, 2010
• Primary Completion: August 28, 2010
• Study Completion: August 28, 2010
• Last Updated: June 8, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)