Phase 0 Microdose Study

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00975936
First received: September 11, 2009
Last updated: January 28, 2010
Last verified: January 2010
  Purpose

This study is a methodology study to evaluate a microdose strategy for Drug-Drug Interaction (DDI) which will be useful in the evaluation of the backup compounds for GSK706769, as well as possibly other assets. The safety, tolerability and pharmacokinetics will be evaluated in healthy adult subjects. This will be an open-label fixed-sequence 2-period study in healthy male volunteers after oral administration of [14C]-GSK706769 alone and in the presence of Ketoconazole.


Condition Intervention Phase
Healthy
Drug: Ketoconazole
Drug: [14C]-GSK706769
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Human Phase 0, Microdose Drug-Drug Interaction Study With [14C]-GSK706769 and Ketoconazole in Healthy Male Volunteers

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Cmax, Tmax, AUC0-t. AUC0-infinity, total plasma clearance (CL/F), apparent volume of distribution (V/F) and terminal phase half-life (t1/2) will also be calculated where data permit. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical safety and tolerability data including spontaneous Adverse Event reporting, ECGs, vital signs, nursing/physician observation, physical examination and clinical laboratory values. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: September 2009
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: [14C]-GSK706769
Single dose of 50µg [14C]-GSK706769 containing 250 nCi
Drug: [14C]-GSK706769
50µg [14C]-GSK706769 containing 250 nCi
Experimental: [14C]-GSK706769 + Ketoconazole
An oral, 5-day repeat dose of 200 mg Ketoconazole (Q12) with a concomitant single oral dose of 50 µg [14C]-GSK706769 containing 250 nCi on day 3.
Drug: Ketoconazole
200 mg Ketoconazole (Q12)
Drug: [14C]-GSK706769
50µg [14C]-GSK706769 containing 250 nCi

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Males 18-50 years of age inclusive, at the time of signing the informed consent.
  • AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5x Upper Limit of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Signed written informed consent prior to beginning study-related procedures. Subjects must understand the aims, investigational procedures and possible consequences of the study and must be able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
  • 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 Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 7 days post-last dose.
  • Body weight greater than or equal to 50 kg (110 pounds) and body mass index (BMI) between 19 and 35 kg/m2 (inclusive)
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Average QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

Exclusion Criteria:

  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • A positive pre-study drug/alcohol screen.
  • A positive test for HIV antibody.
  • History of regular alcohol consumption within 6 months of the study defined in the protocol.
  • 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.
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • History of sensitivity to any of the study medications (including Ketoconazole), or components thereof or a history of drug or other allergy that, in the opinion of the investigator or 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.
  • Any medical or surgical conditions that might significantly interfere with the gastrointestinal absorption, distribution, metabolism, or excretion of the study drugs (eg, gastrectomy).
  • Subjects who have been involved in a 14C human research study within the previous 12 months.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Subject is mentally or legally incapacitated.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • 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 until the completion of the study.
  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: NCT00975936

Locations
United States, Wisconsin
GSK Investigational Site
Madison, Wisconsin, United States, 53704
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00975936     History of Changes
Other Study ID Numbers: 113191
Study First Received: September 11, 2009
Last Updated: January 28, 2010
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by GlaxoSmithKline:
Phase 0
Microdose
Ketoconazole
Drug-Drug Interaction

Additional relevant MeSH terms:
Ketoconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014