Bioequivalence and Food Effect Study in Healthy Volunteers

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

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.

Study Overview

• Status: Completed
• 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

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

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Veneto
    • Verona, Veneto, Italy, 37134
      • 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: Male

Description

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.

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

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Healthy male subjects; 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; 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.; Other Names: SB-649868; Drug: Formulation B; 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.; Drug: Formulation C; Formulation C will represent SB-649868 10 mg lipophilic capsule (3 capsules to reach 30 mg). Formulation C will be administered in Part A.; Drug: Formulation D; 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.; Drug: Formulation E; 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.; Drug: Formulation F; 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.; Drug: Formulation G; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2007
• Primary Completion (Actual): September 26, 2007
• Study Completion (Actual): September 26, 2007

Study Registration Dates

• First Submitted: June 29, 2007
• First Submitted That Met QC Criteria: June 29, 2007
• First Posted (Estimate): July 3, 2007

Study Record Updates

• Last Update Posted (Actual): August 7, 2017
• Last Update Submitted That Met QC Criteria: August 4, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Food effect; pharmacodynamic; Bioequivalent; Reference formulation; 5 new formulation
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders
• Other Study ID Numbers: OXS105205