Clinical trial NCT00489255: Safety/Efficacy of Tigan® to Control Nausea/Vomiting Experienced During Apokyn® Initiation and Treatment
Official title: A Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of Trimethobenzamide (Tigan®) in the Control of Nausea and Vomiting During Initiation and Continued Treatment With Subcutaneous Apomorphine (Apokyn®) in Apomorphine-naïve Subjects With Parkinson's Disease Suffering From Acute Intermittent "Off" Episodes, With Phased Withdrawal of Subjects From Tigan® to Placebo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson's Disease
Keywords: Parkinson's disease
Anti-emetic
Nausea
Vomiting
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
Collaborators: name: INC Research Limited
First posted: 2007-06-21
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purposes of the study are to determine:

i. To assess the efficacy of Tigan® (trimethobenzamide) in preventing nausea and vomiting when initiating therapy with Apokyn® (apomorphine)

ii. To determine the optimal duration for continuation of Tigan® following initiation of Apokyn® therapy

iii. To assess the safety of Tigan® in combination with Apokyn®

iv. To characterize the pharmacokinetic (PK) profile of apomorphine in subjects treated concomitantly with and without Tigan®

Detailed description: Initial randomization is Tigan or Placebo (3:1) with phased withdrawal of Tigan to Placebo after 4 and 8 weeks. Subjects completing 4 weeks Tigan re-randomized to Tigan or Placebo (2:1) with patients completing 8 weeks Tigan re-randomized to receive Tigan or Placebo (1:1). Subjects randomized to Placebo over the previous 4 weeks assigned to continue on Placebo for the remainder of the study.

Eligibility criteria: Inclusion Criteria:

* Subjects aged 18 years or over
* Subjects with advanced Parkinson's disease with disabling hypomobility ("off" episodes) who are to be initiated with Apokyn® by intermittent subcutaneous injection
* Able to swallow Tigan®/placebo capsules
* Subjects willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
* Women of child bearing potential must have a negative serum pregnancy test (beta hCG) prior to receiving study drug and must be using an appropriate form of contraception
* Willing and able to provide informed consent

Exclusion Criteria:

* Hypersensitive to apomorphine hydrochloride or any of the ingredients of Apokyn® (notably sodium metabisulfite)
* Hypersensitive to trimethobenzamide or any of the ingredients of Tigan®
* Previous treatment with Apokyn®
* Participation in any other clinical trial within 14 days of the present trial
* Contraindications to Apokyn® or Tigan®
* Currently taking, or likely to need to take at any time during the course of the study, any 5HT3 antagonist (ondansetron, alosetron, granisetron, palonosetron or dolasetron)
* Malignant melanoma or a history of previously treated malignant melanoma
* Pregnancy or breast feeding
* Receipt of any investigational (i.e. unapproved) medication within 30 days of starting the present trial
* Any significant medical disorder, condition, concomitant medication or psychiatric disorder according to DSM-IV criteria which would, in the opinion of the investigator, represent a hazard to the subject or prevent the subject from completing the trial

Primary outcomes:
measure: Incidence of Nausea and/or Vomiting During the Initial Titration of Apokyn® at the Visit on Day 1
timeFrame: Day 1 (Period 1, Visit 2)
Secondary outcomes:
measure: Incidence of Nausea and/or Vomiting for Period 1
timeFrame: Days 1-28
measure: Incidence of Nausea and/or Vomiting for Period 2
timeFrame: Days 29-56
measure: Incidence of Nausea and/or Vomiting for Period 3
timeFrame: Days 57-84
measure: Modified Index of Nausea, Vomiting and Retching (INVR) Scores - Total Experience Score for Period 1
timeFrame: Days 1-28
measure: Modified Index of Nausea, Vomiting and Retching (INVR) Scores - Total Experience Score for Period 2
timeFrame: Days 29-56
measure: Modified Index of Nausea, Vomiting and Retching (INVR) Scores - Total Experience Score for Period 3
timeFrame: Days 57-84
measure: Subject Global Evaluation of Randomized Study Medication for Period 1
timeFrame: Day 28 (Visit 3)
measure: Subject Global Evaluation of Randomized Study Medication for Period 2
timeFrame: Day 56 (Visit 4)
measure: Subject Global Evaluation of Randomized Study Medication for Period 3
timeFrame: Day 84 (Visit 5)
measure: Median Time to 'on' for Visit 2/Period 1 Injection 1
timeFrame: Day 1 (Visit 2)
measure: Median Time to 'on' for Visit 2/Period 1 Injection 2
timeFrame: Day 1 (Visit 2)
measure: Median Time to 'on' for Visit 3/End of Period 1 Injection
timeFrame: Day 28
measure: Median Time to 'on' for Visit 4/End of Period 2 Injection
timeFrame: Day 56 (Visit 4)
measure: Median Time to 'on' for Visit 5/End of Period 3 Injection
timeFrame: Day 84 (Visit 5)
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 2, Pre Apokyn Dose, Period 1
timeFrame: Day 1 (Visit 2)
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 3, Pre Apokyn Dose, Period 1
timeFrame: Day 28
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 3, Post Apokyn Dose, Period 1
timeFrame: Day 28
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 4, Pre Apokyn Dose, Period 2
timeFrame: Day 56 (Visit 4)
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 4, Post Apokyn Dose, Period 2
timeFrame: Day 56 (Visit 4)
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 5, Pre Apokyn Dose, Period 3
timeFrame: Day 84 (Visit 5)
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 5, Post Apokyn Dose, Period 3
timeFrame: Day 56 (Visit 4)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Movement Disorder Clinic
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: La Jolla
country: United States
facility: Coastal Neurological Medical Group Inc.
state: California
city: Reseda
country: United States
facility: Neurosearch, Inc.
state: California
city: Ventura
country: United States
facility: Neurosearch II, Inc.
state: California
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Gainesville
country: United States
facility: Neurology at Shands Medical Center
state: Florida
city: Jacksonville
country: United States
facility: University of Florida at Jacksonville
state: Florida
city: Ormond Beach
country: United States
facility: Neurology Associates of Ormond Beach
state: Florida
city: Port Charlotte
country: United States
facility: Charlotte Neurological Services
state: Florida
city: Saint Petersburg
country: United States
facility: Suncoast Neuroscience Associates, Inc.
state: Florida
city: Tampa
country: United States
facility: USF Parkinson's Disease and Movement Disorders Center of Excellence
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Glenview
country: United States
facility: NorthShore University Health System
state: Illinois
city: Des Moines
country: United States
facility: Iowa Health Physicians
state: Iowa
city: Elkridge
country: United States
facility: Parkinson's & Movements Disorders Center of Maryland
state: Maryland
city: Bingham Farms
country: United States
facility: Quest Research Institute
state: Michigan
city: Southfield
country: United States
facility: Henry Ford Health System - Franklin Point
state: Michigan
city: Commack
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Long Island
state: New York
city: Kingston
country: United States
facility: Kingston Neurological Associates
state: New York
city: Raleigh
country: United States
facility: Raleigh Neurology Associates
state: North Carolina
city: Cleveland
country: United States
facility: Neurological Institute, Cleveland Clinic
state: Ohio
city: Dallas
country: United States
facility: Neurology Specialist of Dallas P.A
state: Texas
city: Houston
country: United States
facility: Parkinson's Disease and Movement Disorders Center, Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Neurology Associates, P.A.
state: Texas
city: Tyler
country: United States
facility: East Texas Medical Center
state: Texas
city: Virginia Beach
country: United States
facility: Sentara Neurological Associates
state: Virginia
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: