A Repeat Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK1322322 in Healthy Subjects

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00896558
First received: May 7, 2009
Last updated: January 27, 2011
Last verified: January 2011
  Purpose

This study will be the first repeat dose administration of GSK1322322 to investigate safety, tolerability, and pharmacokinetics in healthy subjects as well as elderly volunteer subjects. The study will also include a P450 probe drug (midazolam) to evaluate the effect of GSK1322322 to inhibit or induce CYP3A4 substrates.


Condition Intervention Phase
Skin Diseases, Infectious
Pneumonia
Infections, Bacterial
Drug: GSK1322322/placebo
Drug: GSK1322322/placebo and midazolam
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Parallel, Randomized, Placebo-Controlled, Repeat Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK1322322 in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • GSK1322322 safety parameters, adverse events , absolute values and changes over time of clinical lab testing, vital signs, electrocardiogram [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • GSK1322322 pharmacokinetic parameters following single dose administration on Day 1 and following repeat administration where applicable on Day 7 and Day 12. [ Time Frame: 15 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PK for midazolam with and without GSK1322322 [ Time Frame: 15 days ] [ Designated as safety issue: No ]
  • Blood PK for GSK1322322 [ Time Frame: 15 days ] [ Designated as safety issue: No ]
  • Urine PK for GSK1322322 [ Time Frame: 15 days ] [ Designated as safety issue: No ]
  • GSK1322322 Age Effect on PK Blood and Urine [ Time Frame: 15 days ] [ Designated as safety issue: No ]

Enrollment: 52
Study Start Date: May 2009
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A
A single AM dose of GSK1322322/placebo on Day 1, no dosing on Day 2, and BID dosing on Days 3-12.
Drug: GSK1322322/placebo
GSK1322322/placebo escalating doses from 500mg to 1500mg
Experimental: Cohort B
Subjects will receive a single AM dose of GSK1322322/placebo on Day 1, no dosing on Day 2, and BID dosing on Days 3-12.
Drug: GSK1322322/placebo
GSK1322322/placebo escalating doses from 500mg to 1500mg
Experimental: Cohort C
Subjects in the probe cohort will receive a single AM dose of GSK1322322/placebo on Day 1, no dosing on Day 2, and BID dosing on Days 3-12. All subjects will receive a single dose of midazolam alone on Day -1, and co-administered with the morning dose of GSK1322322/placebo on Day 1 and Day 12.
Drug: GSK1322322/placebo
GSK1322322/placebo escalating doses from 500mg to 1500mg
Drug: GSK1322322/placebo and midazolam
GSK1322322/placebo and 5mg midazolam
Experimental: Cohort D
Subjects will receive a single AM dose of GSK1322322/placebo on Day 1, no dosing on Day 2, and BID dosing on Days 3-12.
Drug: GSK1322322/placebo
GSK1322322/placebo escalating doses from 500mg to 1500mg
Experimental: Cohort E
Subjects will receive a single AM dose of GSK1322322/placebo on Day 1, no dosing on Day 2, and BID dosing on Days 3-12.
Drug: GSK1322322/placebo
GSK1322322/placebo escalating doses from 500mg to 1500mg

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • The subject is healthy.
  • Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent (except for elderly cohort-Part B, see #8 below)..
  • A female is eligible to enter and participate in this study if she is of non-childbearing potential
  • Male subjects must agree to use one of the contraception methods in the protocol
  • Body weight greater than or equal to 50 kg and body mass index between 18.5-29.9 kg/m2 inclusive
  • Capable of giving written informed consent
  • QTcB less than 450 msec; or QTc less than 480 msec in subjects with Bundle Branch Block on Screening ECG
  • Part B/Cohort E Elderly cohort: The subject is greater than 65 years of age.

Exclusion Criteria:

  • The subject has a positive pre-study drug/alcohol screen.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
  • 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 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 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.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Pregnant females as determined by positive human chorionic gonadotropin test at screening or prior to dosing.
  • Lactating females.
  • Subjects who have asthma or a history of asthma within the past 6 months.
  • History of smoking or history of regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
  • Consumption of red wine, seville oranges, grapefruit or grapefruit juice, pummelos, satsuma, ugli, tangerine, and tangelo, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
  • For probe cohort in Part A: any condition or symptom contraindicated for administration of midazolam including acute narrow-angle or open-angle glaucoma.
  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: NCT00896558

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

Responsible Party: E.D. Derilus; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00896558     History of Changes
Other Study ID Numbers: 112668
Study First Received: May 7, 2009
Last Updated: January 27, 2011
Health Authority: Australia: Medicines Australia

Keywords provided by GlaxoSmithKline:
GSK1322322, repeat dose, healthy subjects, elderly, drug-drug interaction, probe, midazolam, double-blind

Additional relevant MeSH terms:
Bacterial Infections
Communicable Diseases
Infection
Skin Diseases
Skin Diseases, Infectious
Midazolam
Adjuvants, Anesthesia
Anesthetics
Anesthetics, General
Anesthetics, Intravenous
Anti-Anxiety Agents
Central Nervous System Agents
Central Nervous System Depressants
GABA Agents
GABA Modulators
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 23, 2014