A Double-blind, Placebo-controlled, Randomised, 2-way Crossover Drug Interaction Study to Investigate the Pharmacokinetic and Pharmacodynamic Effects Following Co-administration of GW642444M With Ketoconazole

GlaxoSmithKline1 site in 1 country20 target enrollmentDecember 22, 2008

ConditionsPulmonary Disease, Chronic Obstructive

InterventionsKetoconazole + GW642444M Placebo + GW642444M

DrugsKetoconazole + GW642444M Placebo + GW642444M

Overview

Phase: Phase 1
Intervention: Ketoconazole + GW642444M
Conditions: Pulmonary Disease, Chronic Obstructive
Sponsor: GlaxoSmithKline
Enrollment: 20
Locations: 1
Primary Endpoint: Supine heart rate and blood potassium levels
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This will be a single-centre, randomised, double blind, placebo controlled, two-way crossover study in healthy male and female subjects. There will be two treatment periods each consisting of 7 days. During each treatment period subjects will receive single doses of ketoconazole or placebo on the morning of days 1-6 with a single dose of GW642444M on the morning of Day 5.

Detailed Description

Registry

clinicaltrials.gov

Start Date

December 22, 2008

End Date

March 27, 2009

Last Updated

8 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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 at the discretion of the Investigator only if the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
•AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
•Male or female between 18 and 65 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, hysterectomy or bilateral oophorectomy; 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 enrolment. 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 after the final follow-up visit has been completed.
•Body weight ≥ 50 kg and BMI within the range 19 - 29.9 kg/m2 (inclusive).
•Demonstrated ability to use the inhaler device in a satisfactory and repeatable manner
•Subjects who are current non-smokers, who have not used any inhaled tobacco products (snuff is permitted) in the 12 month period preceding the screening visit and who have a pack history of ≤ 10 pack years.
•No significant abnormality on 12-lead ECG at screening, including the following requirements:

Exclusion Criteria

•As a result of medical interview, physical examination or screening investigations, the principle investigator or delegate physician deems the subject unsuitable for the study.
•Systolic blood pressure which is outside the range 90 to 140 mmHg, diastolic blood pressure outside the range 50 to 90 mmHg or heart rate outside the range 40 to 90 bpm.
•The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness.
•The subject has any history of breathing problems in adult life (i.e. history of asthmatic symptomatology).
•A clinically significant abnormality on standard pulmonary function testing, or any other finding that would prevent satisfactory administration of the inhaled study medication.
•Any contraindication to the administration of ketoconazole, as described in the current \[NIZORAL Product Information, Janssen-Cilag Pty Limited, 2008\].
•History of sensitivity to any of the study medications, or components thereof (including milk protein) or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
•Currently taking regular (or a course of) medication whether prescribed or not, with the exception of those permitted medications listed in Section 8.1 and Section 9.
•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.
•History of regular alcohol consumption within 6 months of the study defined as: