A Study to Evaluate the Effect of Single Doses of Drug A (Lamotrigine) and Drug B (Vofopitant) Alone and in Combination on Resting Motor Threshold in Healthy Subjects

Double Blind, Double-dummy, Randomised, Placebo Controlled Study to Evaluate the Effect of Single Doses of Drug A (Lamotrigine) and Drug B (Vofopitant) Alone and in Combination on Resting Motor Threshold in Healthy Subjects

The purpose of this study is to investigate the effect of drug A on its own and when it is given in combination with drug B on markers of brain activity. The study will

1. Assess the effects of drug A and drug B on muscle movement after brain stimulation;
2. Examine how the body handles (absorbs, distributes, breaks down and gets rid of) drug A and drug B when given in combination;
3. Examine the safety of drug A and drug B when given together.

Study Overview

• Status: Terminated
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Vofopitant; Drug: Lamotrigine

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Niedersachsen
    • Goettingen, Niedersachsen, Germany, 37075
      • 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 subject
• Male aged 18-65
• Greater than 50kg weight
• BMI 19-29.9 kg/m2

Exclusion Criteria:

• Positive drug/alcohol screen
• Positive HIV antibody
• History of drug dependence
• History of neurological disease
• Pacemaker
• Smoker

Study Plan

How is the study designed?

Design Details

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

Number of Arms

20

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment sequence A; Subjects on sequence A will receive single dose of vofopitant 10 milligrams capsule in part 1, single doses of lamotrigine 175 milligrams tablet + vofopitant 10 milligrams capsule in session A of part 2 and placebo + vofopitant 10 milligrams capsule in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence B; Subjects on sequence B will receive single dose of vofopitant 10 milligrams capsule in part 1, single doses of placebo + vofopitant 10 milligrams capsule in session A of part 2 and lamotrigine 175 milligrams tablet + vofopitant 10 milligrams capsule in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence C; Subjects on sequence C will receive single dose of placebo in part 1, single doses of lamotrigine 175 milligrams tablet + vofopitant 10 milligrams capsule in session A of part 2 and placebo + vofopitant 10 milligrams capsule in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence D; Subjects on sequence D will receive single dose of placebo in part 1, single doses of placebo + vofopitant 10 milligrams capsule in session A of part 2 and lamotrigine 175 milligrams tablet + vofopitant 10 milligrams capsule in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence E; Subjects on sequence E will receive single dose of vofopitant 10 milligrams capsule in part 1, single doses of lamotrigine 175 milligrams tablet + vofopitant 10 milligrams capsule in session A of part 2 and placebo + placebo in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence F; Subjects on sequence F will receive single dose of vofopitant 10 milligrams capsule in part 1, single doses of placebo + placebo in session A of part 2 and lamotrigine 175 milligrams tablet + vofopitant 10 milligrams capsule in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence G; Subjects on sequence G will receive single dose of placebo in part 1, single doses of lamotrigine 175 milligrams tablet + vofopitant 10 milligrams capsule in session A of part 2 and placebo + placebo in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence H; Subjects on sequence H will receive single dose of placebo part 1, single doses of placebo + placebo in session A of part 2 and lamotrigine 175 milligrams tablet + vofopitant 10 milligrams capsule in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence I; Subjects on sequence I will receive single dose of vofopitant 10 milligrams capsule in part 1, single doses of lamotrigine 175 milligrams tablet + placebo in session A of part 2 and placebo + vofopitant 10 milligrams capsule in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence J; Subjects on sequence J will receive single dose of vofopitant 10 milligrams capsule in part 1, single doses of placebo + vofopitant 10 milligrams capsule in session A of part 2 and lamotrigine 175 milligrams tablet + placebo in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence K; Subjects on sequence K will receive single dose of placebo in part 1, single doses of lamotrigine 175 milligrams tablet + placebo in session A of part 2 and placebo + vofopitant 10 milligrams capsule in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence L; Subjects on sequence L will receive single dose of placebo in part 1, single doses of placebo + vofopitant 10 milligrams capsule in session A of part 2 and lamotrigine 175 milligrams tablet + placebo in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence M; Subjects on sequence M will receive single dose of vofopitant 10 milligrams capsule in part 1, single doses of lamotrigine 175 milligrams tablet + placebo in session A of part 2 and placebo + placebo in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence N; Subjects on sequence N will receive single dose of vofopitant 10 milligrams capsule in part 1, placebo + placebo in session A of part 2 and lamotrigine 175 milligrams tablet + placebo in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence O; Subjects on sequence O will receive placebo in part 1, single doses of lamotrigine 175 milligrams tablet + placebo in session A of part 2 and placebo + placebo in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence P; Subjects on sequence P will receive placebo in part 1, single doses of placebo + placebo in session A of part 2 and lamotrigine 175 milligrams tablet + placebo in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence Q; Subjects on sequence Q will receive single dose of vofopitant 10 milligrams capsule in part 1, single doses of lamotrigine 175 milligrams tablet + lamotrigine 150 milligrams tablet in session A of part 2 and placebo + placebo in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence R; Subjects on sequence R will receive single dose of vofopitant 10 milligrams capsule in part 1, single doses of placebo + placebo in session A of part 2 and lamotrigine 175 milligrams tablet + lamotrigine 150 milligrams tablet in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence S; Subjects on sequence S will receive placebo in part 1, single doses of lamotrigine 175 milligrams tablet + lamotrigine 150 milligrams tablet in session A of part 2 and placebo + placebo in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.
Experimental: Treatment sequence T; Subjects on sequence T will receive placebo in part 1, single doses of placebo + placebo in session A of part 2 and lamotrigine 175 milligrams tablet + lamotrigine 150 milligrams tablet in session B of part 2.	Drug: Placebo; Single dose of placebo will be provided.; Drug: Vofopitant; Vofopitant (GR205171) will be provided as 5 milligram single dose capsule administered orally. It will be available as swedish orange, size 0 capsules.; Drug: Lamotrigine; Lamotrigine will be provided as 25 milligrams or 100 milligrams single dose dispersible tablet administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Effect of the study treatments on Resting Motor Thresholds (rMT)	Within 24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
The safety and tolerability of the combination of study treatments.	Within 24 hours

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2009
• Primary Completion (Actual): June 10, 2010
• Study Completion (Actual): June 10, 2010

Study Registration Dates

• First Submitted: May 7, 2009
• First Submitted That Met QC Criteria: May 21, 2009
• First Posted (Estimate): May 25, 2009

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Healthy Volunteer; Transcranial magnetic stimulation (TMS); Resting motor threshold (rMT)
• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Neurokinin-1 Receptor Antagonists; Lamotrigine; Vofopitant
• Other Study ID Numbers: 112676

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: 112676
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 112676
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 112676
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 112676
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 112676
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 112676
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: 112676
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register