Bioequivalence and Food Effect Study in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to select the formulation with the optimal pharmacokinetic profile for an hypnotic drug to further develop in the market.

Detailed Description
-----------------
A single-centre, open-label, randomized, single-dose, 6-way crossover study to investigate the pharmacokinetics, safety and tolerability of 6 different formulations of SB-649868 30 mg (Part A) and the effect of food on the selected formulation of SB-649868 pharmacokinetic (Part B) in healthy male volunteers

Official Title
-----------------
A Single-centre, Open-label, Randomized, Single-dose, 6-way Crossover Study to Investigate the Pharmacokinetics, Safety and Tolerability of 6 Different Formulations of SB-649868 30 mg (Part A) and the Effect of Food on the Selected Formulation of SB-649868 Pharmacokinetic (Part B) in Healthy Male Volunteers

Conditions
-----------------
Sleep Initiation and Maintenance Disorders

Intervention / Treatment
-----------------
* Drug: Formulation A
* Drug: Formulation B
* Drug: Formulation C
* Drug: Formulation D
* Drug: Formulation E
* Drug: Formulation F
* Drug: Formulation G


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Healthy adult male subjects aged between 18 and 65 years of age inclusive. Body weight and BMI within the protocol ranges. Healthy as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests, cardiac monitoring. Circulating levels of LH, FSH and testosterone within the normal reference range. Signed and dated written informed consent. The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions. Exclusion criteria: Positive pre-study urine drug screen and alcohol breath test. Positive pre-study Hepatitis B surface antigen, Hepatitis C antibody, or HIV ½ result. Abuse of alcohol as per protocol criteria. Consumption of prohibited food and drink as per protocol. Subject who is not prepared to eat the standard meals provided by the site. Use of prescription or non-prescription drugs 1 or 2 weeks before the first dose of study medication. Where participation in study would result in donation of blood in excess of 500mL within a 56 day period. History or presence of allergy to the study drug or drugs of this class, or a history of other allergy. Smoking history in the last three months as per protocol. An unwillingness of male subjects to follow contraception methods as per protocol. History or presence of significant psychiatric, respiratory or gastrointestinal illnesses, hepatic or renal diseases or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. The subject is unable or unwilling to abstain from strenuous physical activity in the 48 hours before screening and in the 48 hours before and the 48 hours after the treatment period. Current or previous (within 6 months) participation in a clinical trial.

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: Healthy male subjects<br>In Part A each subject will participate in six sessions and will be administered, in randomized order, single doses of five new formulations (formulation B, C, D, E and F) of SB-649868 30 milligrams (mg), in fasted state and a single dose of the original formulation (formulation A), after a standard Food and Drug Administration (FDA) High-Fat breakfast. All dosing sessions will be separated by a washout session of at least 5 ± 2 days after each dose. In Part B a single dose of the selected SB-649868 30 mg formulation will be administered after a standard FDA High-Fat breakfast. | Drug: Formulation A<br>* Formulation A represents the original formulation. SB-649868 10 mg film coated tablet (3 tablets to reach 30 mg), containing micronized drug substance. Formulation A will be administered in Part A.<br>* Other names: SB-649868;Drug: Formulation B<br>* Formulation B will represent SB-649868 10 mg film coated tablet containing micronized drug substance (3 tablets to reach 30 mg), but contains additional surfactant. Formulation B will be administered in Part A.<br>Drug: Formulation C<br>* Formulation C will represent SB-649868 10 mg lipophilic capsule (3 capsules to reach 30 mg). Formulation C will be administered in Part A.<br>Drug: Formulation D<br>* Formulation D will represent SB-649868 10 mg film coated tablet (3 tablets to reach 30 mg), containing nanomilled and spray dried powder. Formulation D will be administered in Part A.<br>Drug: Formulation E<br>* Formulation E will represent SB-649868 10 mg capsule (3 capsules to reach 30 mg), containing nanomilled and spray dried powder. Formulation E will be administered in Part A.<br>Drug: Formulation F<br>* Formulation F will represent SB-649868 15 mg liquid filled capsule (2 capsules to reach 30 mg). Formulation F will be administered in Part A.<br>Drug: Formulation G<br>* Formulation G will be the selected formulation of SB-649868 30 mg to be assessed in Part B. The formulation will be administered after a standard FDA High-Fat breakfast<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| -Part A: SB-649868 levels of 6 formulation predose, 0.5, 1, 1.5, 2,3,4,5,6,8,12 and 24hours post-dose |  | predose, 0.5, 1, 1.5, 2,3,4,5,6,8,12 and 24hours post-dose | 
| -Part B: SB-649868 levels of selected formulation after food at the same timepoints as in Part A |  | predose, 0.5, 1, 1.5, 2,3,4,5,6,8,12 and 24hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| -AE, Lab values and cardiovascular monitoring throughout study participation |  | throughout study participation | 
| -Romberg heel-to-toe test at discharge |  | at discharge | 
| -Cognitive functions predose, 0.5, 1, 2, 4, 6 hours post-dose |  | predose, 0.5, 1, 2, 4, 6 hours post-dose | 
| Pharmacodynamic endpoint: Bond Lader Visual Analogue Scale (VAS) score |  | pre-dose, 0.5, 1, 2, 4, 6 hours post-dose on Day 1 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bioequivalent, pharmacodynamic, Reference formulation, 5 new formulation, Food effect, Pharmacokinetics