Healthy Volunteer Study Using 3 Different Formulations of Firategrast

A Single/Repeat Dose Study With Three Oral Formulations of Firategrast (Immediate Release Tablet, Modified Release Tablet, and Naso-gastric Infusion) in Healthy Male Volunteers

This study will investigate how 3 types of drug formulations are absorbed by the body. This study is termed 'open-label', which means volunteers will be aware of which treatment they are receiving. The study is split into 2 parts. Part 1, involves volunteers receiving 2 new formulations, as a single dose. There is no placebo (dummy-drug; no active ingredient) in this study. Volunteers will also receive a single dose of a formulation used in previous trials (reference formulation), so a proper comparison with the new formulations can be made. The new fomulations will be administered with food and the reference formulation will be given without food. In Part 2, volunteers will receive only one of the 3 formulations as a repeat dose for 7 days. Each of these doses will be given with food.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Drug: Firategrast immediate release tablet; Drug: Firategrast modified release tablet; Drug: Firategrast gastro-retentive solution

Detailed Description

The present study will be conducted in two parts in healthy male volunteers. Part 1 will investigate the pharmacokinetics and tolerability of single doses of firategrast administered as the existing immediate release tablet formulation, as a modified release tablet (3hr) formulation and as a simulated gastro-retentive formulation to be administered via a naso-gastric tube. Subjects will receive each formulation in a randomised 3-way single dose crossover fashion.

Part 2, based on the review of safety, tolerability and pharmacokinetic data from the first two study treatment periods of Part 1, will investigate the pharmacokinetics and tolerability of multiple doses of firategrast administered as the existing immediate release tablet formulation, as a modified release tablet (3hr) formulation and as simulated gastro-retentive formulation to be administered via naso-gastric tube for a period of 7 days.

• Study Type: Interventional
• Enrollment (Actual): 38
• 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: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male aged 18 to 65 yrs inclusive
• Healthy, as determined by study physician
• Capable of giving iformed consent

Exclusion Criteria:

• Positive drugs of abuse result
• Positive for HIV or Hepatitis B and/or C viruses
• History of alcohol consumption in excess of average recommended weekly intake (more than 12 units for males)
• Participation in a clinical trial within 30 days of scheduled first dose

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm ACB: Part 1; Subjects will receive treatment sequence ACB; A : Firategrast immediate release tablet 1200 milligram (mg) once only orally, C : Firategrast simulated gastro-retentive solution 1200 mg once only by naso-gastric route, B : Firategrast 3 hour release tablet 1200 mg once only orally. There will be a washout period of 5 days between doses.	Drug: Firategrast immediate release tablet; Firategrast immediate release tablet is white to pale cream colored 300 mg unit dose and subjects will administer it with 240 milliliter (mL) of water.; Drug: Firategrast modified release tablet; Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.; Drug: Firategrast gastro-retentive solution; Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.
Experimental: Treatment Arm BAC: Part 1; Subjects will receive treatment sequence BAC; B : Firategrast 3 hour release tablet 1200 mg once only orally, A : Firategrast immediate release tablet 1200 mg once only orally, C : Firategrast simulated gastro-retentive solution 1200 mg once only by naso-gastric route. There will be a washout period of 5 days between doses.	Drug: Firategrast immediate release tablet; Firategrast immediate release tablet is white to pale cream colored 300 mg unit dose and subjects will administer it with 240 milliliter (mL) of water.; Drug: Firategrast modified release tablet; Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.; Drug: Firategrast gastro-retentive solution; Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.
Experimental: Treatment Arm CBA: Part 1; Subjects will receive treatment sequence CBA; C : Firategrast simulated gastro-retentive solution 1200 mg once only by naso-gastric route, B : Firategrast 3 hour release tablet 1200 mg once only orally, A : Firategrast immediate release tablet 1200 mg once only orally. There will be a washout period of 5 days between doses.	Drug: Firategrast immediate release tablet; Firategrast immediate release tablet is white to pale cream colored 300 mg unit dose and subjects will administer it with 240 milliliter (mL) of water.; Drug: Firategrast modified release tablet; Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.; Drug: Firategrast gastro-retentive solution; Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.
Experimental: Treatment Arm BCA: Part 1; Subjects will receive treatment sequence BCA; B : Firategrast 3 hour release tablet 1200 mg once only orally, C : Firategrast simulated gastro-retentive solution 1200 mg once only by naso-gastric route, A : Firategrast immediate release tablet 1200 mg once only orally. There will be a washout period of 5 days between doses.	Drug: Firategrast immediate release tablet; Firategrast immediate release tablet is white to pale cream colored 300 mg unit dose and subjects will administer it with 240 milliliter (mL) of water.; Drug: Firategrast modified release tablet; Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.; Drug: Firategrast gastro-retentive solution; Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.
Experimental: Treatment Arm CAB: Part 1; Subjects will receive treatment sequence CAB; C : Firategrast simulated gastro-retentive solution 1200 mg once only by naso-gastric route, A : Firategrast immediate release tablet 1200 mg once only orally, B : Firategrast 3 hour release tablet 1200 mg once only orally. There will be a washout period of 5 days between doses.	Drug: Firategrast immediate release tablet; Firategrast immediate release tablet is white to pale cream colored 300 mg unit dose and subjects will administer it with 240 milliliter (mL) of water.; Drug: Firategrast modified release tablet; Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.; Drug: Firategrast gastro-retentive solution; Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.
Experimental: Treatment Arm ABC: Part 1; Subjects will receive treatment sequence ABC; A : Firategrast immediate release tablet 1200 mg once only orally, B : Firategrast 3 hour release tablet 1200 mg once only orally, C : Firategrast simulated gastro-retentive solution 1200 mg once only by naso-gastric route. There will be a washout period of 5 days between doses.	Drug: Firategrast immediate release tablet; Firategrast immediate release tablet is white to pale cream colored 300 mg unit dose and subjects will administer it with 240 milliliter (mL) of water.; Drug: Firategrast modified release tablet; Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.; Drug: Firategrast gastro-retentive solution; Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.
Experimental: Treatment Arm D: Part 2; Subject will receive D: Firategrast immediate release tablet 600 mg twice daily for 7 days	Drug: Firategrast immediate release tablet; Firategrast immediate release tablet is white to pale cream colored 300 mg unit dose and subjects will administer it with 240 milliliter (mL) of water.; Drug: Firategrast modified release tablet; Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.; Drug: Firategrast gastro-retentive solution; Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.
Experimental: Treatment Arm E: Part 2; Subject will receive E: Firategrast 3 hour release tablet 1200 mg twice daily for 7 days	Drug: Firategrast immediate release tablet; Firategrast immediate release tablet is white to pale cream colored 300 mg unit dose and subjects will administer it with 240 milliliter (mL) of water.; Drug: Firategrast modified release tablet; Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.; Drug: Firategrast gastro-retentive solution; Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.
Experimental: Treatment Arm F: Part 2; Subject will receive F: Firategrast simulated gastro-retentive solution 1200 mg twice daily for 7 days	Drug: Firategrast immediate release tablet; Firategrast immediate release tablet is white to pale cream colored 300 mg unit dose and subjects will administer it with 240 milliliter (mL) of water.; Drug: Firategrast modified release tablet; Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.; Drug: Firategrast gastro-retentive solution; Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic measures for single and repeat dose	Cmax of firategrast	Part 1: approx. 4 weeks, Part 2: approx 8 days
PK measures for single and repeat dose	AUC(0-t) of firategrast	Part 1 approx 4 weeks, Part 2 approx 8 days
Pharmacokinetic measurements for single and repeat dose	AUC(0-24) of firategrast	Part 1: approx 4 weeks, Part 2: approx 8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety & Tolerability in single and repeat doses	Adverse events, changes iin blood pressure, heart rate, ECGs, Haematology, clinical chemistry and urinalysis	Part 1: approx. 4 weeks, Part 2: approx 8 days
CD34 positive cell count	as data permit - exploratory measure	Part 1 only approx 4 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2011
• Primary Completion (Actual): September 17, 2011
• Study Completion (Actual): September 17, 2011

Study Registration Dates

• First Submitted: June 23, 2011
• First Submitted That Met QC Criteria: August 11, 2011
• First Posted (Estimate): August 15, 2011

Study Record Updates

• Last Update Posted (Actual): July 7, 2017
• Last Update Submitted That Met QC Criteria: July 5, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: pharmacokinetics; healthy volunteers; modified release; firategrast; pharmacokinetics, modified release, firategrast,; simulated gastro-retentive; healthy volunteers, simulated gastro-retentive
• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: 115517