Single and Multiple Ascending Dose Study of V158866 in Healthy Volunteers

A Double-blind, Randomised, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Oral Doses of V158866 in Healthy Volunteers

The purpose of this study is to investigate whether V158866 is safe when given to healthy male subjects in single and multiple doses.

Study Overview

• Status: Completed
• Conditions: First in Man Study
• Intervention / Treatment: Drug: V158866; Drug: V158866

Detailed Description

A first in human study:

To evaluate the safety and tolerability of single and multiple doses of V158866 in healthy male subjects To assess the pharmacokinetics (PK) of V158866 in healthy male subjects To assess the pharmacodynamics (PD) of V158866 by determining whether V158866 inhibits fatty acid amide hydrolase (FAAH ) in healthy male subjects

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW10 7EW
    • Hammersmith Medicines Research Limited

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Subjects must:

• be healthy male subjects aged 18 to 45 years inclusive
• Have a body mass index (BMI) between 19 and 30 kg/m2 inclusive
• be able to provide a semen sample
• be willing to use an effective method of contraception (see Section 6.1) for the duration of the study and for 4 months after the last dose of study medication
• be able to comply with the requirements of the entire study
• give written informed consent

Exclusion Criteria:

Subjects must not:

• intend to father a child with their female partner or through sperm donation within 4 months after the last dose of study medication
• have had a vasectomy
• have a significant medical condition or a history of such a condition that the Investigator considers should exclude the subject from the study
• have multiple drug allergies or be allergic to any of the components of V158866 study medication or its matching placebo (see Section 7)
• have smoked more than 5 cigarettes per day in the 6 calendar months before study drug administration
• consume more than 28 units of alcohol per week, or have a significant history of alcohol abuse
• have a positive test for alcohol or drugs of abuse at screening or admission to any of the dosing sessions
• have donated blood or plasma in excess of 500 mL within 4 months before study drug administration
• have been exposed to any new investigational agent within 3 months before study drug administration
• have clinically relevant abnormal findings on vital signs
• have clinically significant abnormalities on laboratory screening tests
• have clinically relevant abnormal physical findings on examination
• have clinically relevant abnormal findings on 12-lead ECG
• have a mean QTc corrected using Bazett's correction (QTcB) at screening >430 msec (from 3 supine ECGs, performed at least 5 minutes apart)
• be seropositive for hepatitis B, hepatitis C or HIV viruses at screening
• have any medical or social reasons for not participating in the study raised by their General Practitioner/primary care physician
• have any other condition that might increase the risk to the individual or decrease the chance of obtaining satisfactory data, as assessed by the Investigator
• have had treatment with any prescription medicine within one month or any over-the-counter medicines, except for paracetamol, within one week before study drug administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Ascending Dose; Single ascending doses of V158866 compared to Placebo	Drug: V158866; Single ascending oral doses of V158866 and Placebo; Drug: V158866; Multiple ascending oral doses of V158866 and Placebo
Experimental: Multiple ascending doses; Multiple ascending doses of V158866 compared to Placebo	Drug: V158866; Single ascending oral doses of V158866 and Placebo; Drug: V158866; Multiple ascending oral doses of V158866 and Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate the safety of V158866 by assessing adverse events	Throughout the dosing phase with specific enquiries pre-dose and at 1, 2, 8, 24, 48 and 72 hours post-dose and at the post-study visit.
Evaluate the safety of V158866 by assessing vital signs	screen, Day -1, before and after each dose of V158866 or placebo (within 1 hour pre-dose and at 30 minutes (supine/semi-recumbent only), 1, 2, 3, 4, 8, 12, 24, 36, 48, 72 hours post-dose), post-study visit.
Evaluate the safety of V158866 by assessing ECGs	At screen, before and after each dose of V158866 or placebo (within 1 hour pre-dose and at 1, 2, 4, 8, 12, 24 and 72 hours post-dose), post-study visit.
Evaluate the safety of V158866 by assessing safety labs	At screen, Day 1, 24 hours and 72 hours after each dose of V158866 or placebo, and at the post-study visit.

Secondary Outcome Measures

Outcome Measure	Time Frame
Blood concentration profile of V158866	Samples will be collected within 15 minutes pre-dose and at 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, 48 and 72 hours after each dose
Measurement of FAAH activity and endocannabinoids	Up to 7 days post dosing

Collaborators and Investigators

• Sponsor: Vernalis (R&D) Ltd
• Investigators: Principal Investigator: Steve Warrington, MD, Hammersmith Medicines Research Limited

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: July 21, 2011
• First Submitted That Met QC Criteria: July 2, 2012
• First Posted (Estimate): July 6, 2012

Study Record Updates

• Last Update Posted (Estimate): July 11, 2012
• Last Update Submitted That Met QC Criteria: July 10, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Other Study ID Numbers: V158866-1Pa-01