Drug Interaction Study to Investigate Co-administration of GW642444M With Ketoconazole

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00866515
First received: January 22, 2009
Last updated: September 3, 2010
Last verified: September 2010
  Purpose

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.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Healthy Subjects
Drug: Ketoconazole + GW642444M
Drug: Placebo + GW642444M
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Supine heart rate and blood potassium levels [ Time Frame: Day 5 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Plasma GW642444M concentrations [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
  • Reported Adverse Events [ Time Frame: treatment periods ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: December 2008
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active
Ketoconazole 400mg OD days 1-6
Drug: Ketoconazole + GW642444M
Ketoconazole 400mg OD days 1-6, GW642444M 25ug single dose on D5
Other Name: Ketoconazole + GW642444M
Placebo Comparator: Placebo Drug: Placebo + GW642444M
Placebo to match D1-6 + GW642444M 25ug single dose on D5
Other Name: Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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:
  • Ventricular rate ≥ 40 beats per minute
  • PR interval ≥ 120 and ≤ 210 msec
  • Q waves < 30 msec (up to 50 msec permitted in lead III only)
  • QRS interval to be ≥ 60 msec and ≤ 120 msec
  • QTc interval must be < 450 msec (QTcB or QTcF; machine or manual reading) based on an average from three ECGs obtained over a brief recording period
  • FEV1 ≥ 80% predicted and a FEV1 / FVC ratio ≥ 0.7 at screening
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

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 9.1.
  • 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:
  • An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~250 mL) of beer, 1 glass (100 mL) of wine or 1 measure (30 mL) of spirits.
  • The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • The subject has donated a unit of blood within the previous 16 weeks or intends to donate within 16 weeks after completing the study.
  • 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.
  • The subject has a positive pre-study urine drug screen/ alcohol breath test. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Subjects who have a screening haemoglobin value < 110 mg/L.
  • Pregnant (as determined by positive (serum or urine) hCG test at screening or prior to dosing) or lactating females.
  • Subject is mentally or legally incapacitated.
  • CO breath monitoring indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00866515

Locations
Australia, New South Wales
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00866515     History of Changes
Other Study ID Numbers: 112205
Study First Received: January 22, 2009
Last Updated: September 3, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Healthy volunteer
pharmacodynamics
Ketoconazole
Drug Interaction
pharmacokinetcs
GW642444M
pharmacokinetics

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Lung Diseases, Obstructive
Ketoconazole
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 09, 2014