Single Dose Escalation First Time in Human PK Study

A Double-Blind, Parallel, Randomized, Placebo-Controlled, Single Dose Escalation First Time in Human Study to Investigate the Safety, Tolerability and Pharmacokinetics of Investigational Study Drug in Healthy Subjects

This is a first time in human (FTIH) study of single escalating doses of investigational study drug to investigate safety, tolerability, and pharmacokinetics in healthy subjects

Study Overview

• Status: Completed
• Conditions: Infections, Bacterial
• Intervention / Treatment: Drug: 100 mg GSK investigational drug; Drug: 200 mg GSK investigational drug; Drug: 400 mg GSK investigational drug; Drug: 800 mg GSK investigational drug; Drug: 1500 mg GSK investigational drug; Drug: 2000 mg GSK investigational drug; Drug: 800mg fed GSK investigational drug; Drug: 3000mg GSK investigational drug; Drug: 4000mg GSK investigational drug

• Study Type: Interventional
• Enrollment (Actual): 41
• 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 to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy
• male
• non-childbearling potential females
• Body weight greater than or equal to 50 kg (110 lbs) for men and greater than or equal to 45 kg (99 lbs) for women. Body mass index (BMI) between 18.5-29.9 kg/m2 inclusive.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
• QTcB < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block on Screening ECG

Exclusion Criteria:

• The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
• 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 as:

an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). A standard unit is defined as 10g ethanol which is equivalent to 100mL wine, 250mL full strength beer, 470mL light beer, 30mL spirits

• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the 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 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 [serum or urine] human chorionic gonadotropin (hCG) 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 100mg	Drug: 100 mg GSK investigational drug; Other Names: selected mg fed study drug; 2000 mg study drug; 800 mg study drug; 400 mg study drug; 200 mg study drug; 100 mg study drug; 1500 mg study drug
Experimental: Cohort 2; 200mg	Drug: 200 mg GSK investigational drug
Experimental: Cohort 3; 400mg	Drug: 400 mg GSK investigational drug
Experimental: Cohort 4; 800mg	Drug: 800 mg GSK investigational drug
Experimental: Cohort 5; 1500mg	Drug: 1500 mg GSK investigational drug
Experimental: Cohort 6; 2000mg	Drug: 2000 mg GSK investigational drug
Experimental: Cohort 7; 800mg with food	Drug: 800mg fed GSK investigational drug
Experimental: Cohort 8; 3000mg	Drug: 3000mg GSK investigational drug
Experimental: Cohort 9; 4000mg	Drug: 4000mg GSK investigational drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety parameters, adverse events, absolute values and changes over time of hematology, clinical chemistry, urinalysis, vital signs, electrocardiogram intervals, and ECG rhythm.	Eighteen days
Pharmacokinetic parameters following single dose administration: area under the plasma concentration curve AUC 0 to inf, AUC 0 to t, AUC 0 to 24, maximum observed concentration , time to maximum observed concentration , terminal half life .	Two days, Three days (3000mg and 4000mg only)

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC 0 to inf and Cmax following single dose administration for the assessment of dose proportionality	Two days, Three days (3000mg and 4000mg only)
Amount excreted of unchanged study drug and renal clearance	Two days, Three days (3000mg and 4000mg only)
AUC 0 to inf, AUC 0 to t, AUC 0 to 24, Cmax, tmax and tlag if deemed appropriate with and without high fat calorie meal	Two days, Three days (3000mg and 4000mg only)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Naderer OJ, Dumont E, Zhu J, Kurtinecz M, Jones LS. Single-dose safety, tolerability, and pharmacokinetics of the antibiotic GSK1322322, a novel peptide deformylase inhibitor. Antimicrob Agents Chemother. 2013 May;57(5):2005-9. doi: 10.1128/AAC.01779-12. Epub 2013 Feb 12.

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): November 14, 2008
• Primary Completion (Actual): December 7, 2009
• Study Completion (Actual): December 7, 2009

Study Registration Dates

• First Submitted: December 8, 2008
• First Submitted That Met QC Criteria: January 22, 2009
• First Posted (Estimate): January 26, 2009

Study Record Updates

• Last Update Posted (Actual): June 20, 2017
• Last Update Submitted That Met QC Criteria: June 19, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: healthy subjects; FTIH, single dose, food effect, healthy subjects, double-blind
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections
• Other Study ID Numbers: 111341

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. Statistical Analysis Plan
   Information identifier: 111341
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 111341
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 111341
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 111341
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 111341
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: 111341
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 111341
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register