Healthy Volunteer Study Using 3 Different Formulations of Firategrast

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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

Conditions
-----------------
Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
-----------------
* Drug: Firategrast immediate release tablet
* Drug: Firategrast modified release tablet
* Drug: Firategrast gastro-retentive solution


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm ACB: Part 1<br>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<br>* 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.<br>Drug: Firategrast modified release tablet<br>* Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.<br>Drug: Firategrast gastro-retentive solution<br>* Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.<br>|
| Experimental: Treatment Arm BAC: Part 1<br>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<br>* 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.<br>Drug: Firategrast modified release tablet<br>* Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.<br>Drug: Firategrast gastro-retentive solution<br>* Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.<br>|
| Experimental: Treatment Arm CBA: Part 1<br>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<br>* 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.<br>Drug: Firategrast modified release tablet<br>* Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.<br>Drug: Firategrast gastro-retentive solution<br>* Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.<br>|
| Experimental: Treatment Arm BCA: Part 1<br>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<br>* 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.<br>Drug: Firategrast modified release tablet<br>* Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.<br>Drug: Firategrast gastro-retentive solution<br>* Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.<br>|
| Experimental: Treatment Arm CAB: Part 1<br>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<br>* 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.<br>Drug: Firategrast modified release tablet<br>* Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.<br>Drug: Firategrast gastro-retentive solution<br>* Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.<br>|
| Experimental: Treatment Arm ABC: Part 1<br>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<br>* 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.<br>Drug: Firategrast modified release tablet<br>* Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.<br>Drug: Firategrast gastro-retentive solution<br>* Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.<br>|
| Experimental: Treatment Arm D: Part 2<br>Subject will receive D: Firategrast immediate release tablet 600 mg twice daily for 7 days | Drug: Firategrast immediate release tablet<br>* 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.<br>Drug: Firategrast modified release tablet<br>* Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.<br>Drug: Firategrast gastro-retentive solution<br>* Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.<br>|
| Experimental: Treatment Arm E: Part 2<br>Subject will receive E: Firategrast 3 hour release tablet 1200 mg twice daily for 7 days | Drug: Firategrast immediate release tablet<br>* 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.<br>Drug: Firategrast modified release tablet<br>* Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.<br>Drug: Firategrast gastro-retentive solution<br>* Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.<br>|
| Experimental: Treatment Arm F: Part 2<br>Subject will receive F: Firategrast simulated gastro-retentive solution 1200 mg twice daily for 7 days | Drug: Firategrast immediate release tablet<br>* 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.<br>Drug: Firategrast modified release tablet<br>* Firategrast modified release tablet is white to slightly colored 600 mg unit dose and subjects will administer it with 240 mL of water.<br>Drug: Firategrast gastro-retentive solution<br>* Firategrast solution is clear colorless solution and subject will administer it via nasogastric route.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
firategrast, pharmacokinetics, modified release, firategrast,, simulated gastro-retentive, pharmacokinetics, healthy volunteers, simulated gastro-retentive, healthy volunteers, modified release