AsthmaPhase 1NCT01165125
A Drug Interaction Study With Fluticasone Furoate/GW642444 Inhalation Powder and Ketoconazole
A Phase 1 study testing FF / GW642444 and ketoconazole in people with Asthma, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- FF / GW642444 and ketoconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jul 2010to 28 Aug 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months of the start of the trial.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- The subject has tested positive for HIV antibodies.
- A positive pre-study urine drug screen or when randomly tested during the study.
- Positive carbon monoxide (CO) or alcohol breath test at screening or on admission to the Unit.
- Consumption of seville oranges, pomelos (members of the grapefruit family) or grapefruit juice from 7 days prior to the first dose of study medication.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-blind, Randomized, Placebo-controlled, Repeat Dose, 2-way Crossover Drug Interaction Study to Investigate the Pharmacokinetic and Pharmacodynamic Effects Following Administration of Fluticasone Furoate/GW642444M Inhalation Powder With Ketoconazole
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.
Read the detailed description
This will be a single centre, randomized, double-blind (with respect to ketoconazole), two-way cross-over study in healthy male and female subjects. Subjects will attend for a screening visit within 28 days prior to the first treatment period. There will be two study periods, each consisting of 14 days. Ketoconazole or matching placebo will be administered for 11 days with fluticasone furoate/GW642444M inhalation powder co-administered on Days 5-11. During each period subjects will be required to report to the unit on Day -1 and will remain there until 1 hour post-dosing with ketoconazole or placebo on Day 1. Subjects will return to the unit on the mornings of Day 2 to Day 4 for dosing with ketoconazole or placebo. Subjects will then return on the evening of Day 4 and leave the unit on the morning of Day 6 (2 nights). Subjects will return to the unit on the mornings of Day 7 to Day 10 for dosing and pre-fluticasone furoate/GW642444M dose safety assessments. Subjects will return on the evening of Day 10 and leave the unit on the morning of Day 12 (2 nights). Subjects will make two outpatient visits, one in the evening on Day 12 and one in the morning on Day 13, to complete a few study related procedures. The two treatment periods will be separated by a washout of at least 7 days and no more than 14 days. Pharmacodynamic profiles for potassium, heart rate, QTc, blood pressure and serum cortisol will be taken on Day 11 with fluticasone furoate and GW642444 pharmacokinetic profiles on Days 5 and 11. Safety assessments will include vital signs, ECGs, adverse event monitoring and laboratory safety tests, plus blood glucose and blood potassium profiles on Day 5.
- Conditions
- Asthma
- Being tested
- FF / GW642444, ketoconazole, ketoconazole (placebo to match)
- Keywords
- pharmacodynamics, drug interaction, ketoconazole, pharmacokinetics, Fluticasone furoate, GW642444
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FF / GW642444Drug
200mcg/25mcg Novel DPI
ketoconazoleDrug
400mcg overencapsulated tablets
ketoconazole (placebo to match)Drug
placebo to match overencapsulated tablets
| Study group | Role | What they receive |
|---|---|---|
| FF/GW642444 and keto | Other | Ketoconazole (400mcg) administered on Days 1-11, with co-administration of fFF / GW642444 (200mcg/25mcg) on Days 5-11 Receives: 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 Receives: Drug: FF / GW642444; Drug: ketoconazole (placebo to match) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum heart rate (0-4 hours) and minimum blood potassium level (0-4 hours) on the morning of Day 11
Measured: Day 11
Weighted mean serum cortisol (0-24 hours) on Day 11.
Measured: 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
Measured: Day 11
Fluticasone furoate and GW642444 pharmacokinetics (AUC(0-t), AUC(0-24), Cmax, tmax) on Day 5 and 11
Measured: day 11
Reported adverse events
Measured: 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.
Measured: Day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2010 (estimated)
- Study start1 Jul 2010
- Primary completion28 Aug 2010
- Study completion28 Aug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01165125
- Sponsor's protocol ID
- 105548
- Status last verified
- Jun 2017
- First submitted
- 15 Jul 2010
- Last updated
- 8 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
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.
PubMed 23116485
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Placebo-controlled, Repeat Dose, 2-way Crossover Drug Interaction Study to Investigate the Pharmacokinetic and Pharmacodynamic Effects Following Administration of Fluticasone Furoate/GW642444M Inhalation Powder With Ketoconazole
- ClinicalTrials.gov ID
- NCT01165125
- Acronym / sponsor ID
- 105548
- Conditions
- Asthma
- Keywords
- pharmacodynamics, drug interaction, ketoconazole, pharmacokinetics, Fluticasone furoate, GW642444
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2010 (actual)
- Primary completion
- 28 Aug 2010 (actual)
- Study completion
- 28 Aug 2010 (actual)
- First posted
- 19 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This will be a single centre, randomized, double-blind (with respect to ketoconazole), two-way cross-over study in healthy male and female subjects. Subjects will attend for a screening visit within 28 days prior to the first treatment period. There will be two study periods, each consisting of 14 days. Ketoconazole or matching placebo will be administered for 11 days with fluticasone furoate/GW642444M inhalation powder co-administered on Days 5-11. During each period subjects will be required to report to the unit on Day -1 and will remain there until 1 hour post-dosing with ketoconazole or placebo on Day 1. Subjects will return to the unit on the mornings of Day 2 to Day 4 for dosing with ketoconazole or placebo. Subjects will then return on the evening of Day 4 and leave the unit on the morning of Day 6 (2 nights). Subjects will return to the unit on the mornings of Day 7 to Day 10 for dosing and pre-fluticasone furoate/GW642444M dose safety assessments. Subjects will return on the evening of Day 10 and leave the unit on the morning of Day 12 (2 nights). Subjects will make two outpatient visits, one in the evening on Day 12 and one in the morning on Day 13, to complete a few study related procedures. The two treatment periods will be separated by a washout of at least 7 days and no more than 14 days. Pharmacodynamic profiles for potassium, heart rate, QTc, blood pressure and serum cortisol will be taken on Day 11 with fluticasone furoate and GW642444 pharmacokinetic profiles on Days 5 and 11. Safety assessments will include vital signs, ECGs, adverse event monitoring and laboratory safety tests, plus blood glucose and blood potassium profiles on Day 5.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FF/GW642444 and keto | Other | Drug: FF / GW642444, Drug: ketoconazoleKetoconazole (400mcg) administered on Days 1-11, with co-administration of fFF / GW642444 (200mcg/25mcg) on Days 5-11 |
| Ketoconazole Placebo to match & FF/GW642444 | Other | Drug: FF / GW642444, Drug: ketoconazole (placebo to match)ketoconazole placebo to match administered on days 1-11. FF/GW642444 (200mcg/25mcg) co-administered on Days 5-11 |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Healthy male or female between 18 and 64 years of age inclusive
- A female subject is eligible to participate if she is of:
- 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%).
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FF / GW642444200mcg/25mcg Novel DPI | Drug | FF/GW642444 and keto, Ketoconazole Placebo to match & FF/GW642444 |
| ketoconazole400mcg overencapsulated tablets | Drug | FF/GW642444 and keto |
| ketoconazole (placebo to match)placebo to match overencapsulated tablets | Drug | Ketoconazole Placebo to match & FF/GW642444 |
Primary outcome
Maximum heart rate (0-4 hours) and minimum blood potassium level (0-4 hours) on the morning of Day 11
Time frame: Day 11
Weighted mean serum cortisol (0-24 hours) on Day 11.
Time frame: Day 11
4 secondary outcomes
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
Time frame: Day 11
Fluticasone furoate and GW642444 pharmacokinetics (AUC(0-t), AUC(0-24), Cmax, tmax) on Day 5 and 11
Time frame: day 11
Reported adverse events
Time frame: 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.
Time frame: Day 5
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2017.
- Background: PubMed 23116485Kempsford 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.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Results for study 105548 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FF / GW642444 and ketoconazole in people with Asthma, run by GlaxoSmithKline at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum heart rate (0-4 hours) and minimum blood potassium level (0-4 hours) on the morning of Day 11 (time frame: Day 11). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01165125, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2017.