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

A Double-Blind, Parallel, Randomized, Placebo-Controlled, Repeat Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK1322322 in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Infections, Bacterial
• Intervention / Treatment: Drug: GSK1322322/placebo; Drug: GSK1322322/placebo and midazolam

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
GSK1322322 safety parameters, adverse events , absolute values and changes over time of clinical lab testing, vital signs, electrocardiogram	6 weeks
GSK1322322 pharmacokinetic parameters following single dose administration on Day 1 and following repeat administration where applicable on Day 7 and Day 12.	15 days

Secondary Outcome Measures

Outcome Measure	Time Frame
PK for midazolam with and without GSK1322322	15 days
Blood PK for GSK1322322	15 days
Urine PK for GSK1322322	15 days
GSK1322322 Age Effect on PK Blood and Urine	15 days

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Naderer OJ, Dumont E, Zhu J, Kurtinecz M, Jones LS. Safety, tolerability and pharmacokinetics of repeat dosing of the antibiotic GSK1322322, a peptide deformylase inhibitor: a randomized placebo-controlled study. J Antimicrob Chemother. 2013 Aug;68(8):1901-9. doi: 10.1093/jac/dkt097. Epub 2013 Apr 3.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2009
• Primary Completion (Actual): September 25, 2009
• Study Completion (Actual): September 25, 2009

Study Registration Dates

• First Submitted: May 7, 2009
• First Submitted That Met QC Criteria: May 7, 2009
• First Posted (Estimate): May 11, 2009

Study Record Updates

• Last Update Posted (Actual): June 22, 2017
• Last Update Submitted That Met QC Criteria: June 21, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: GSK1322322, repeat dose, healthy subjects, elderly, drug-drug interaction, probe, midazolam, double-blind
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: 112668

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Annotated Case Report Form
   Information identifier: 112668
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 112668
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Statistical Analysis Plan
   Information identifier: 112668
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 112668
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 112668
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 112668
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 112668
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register