Safety/Efficacy of Tigan® to Control Nausea/Vomiting Experienced During Apokyn® Initiation and Treatment

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

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®

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Tigan®; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Movement Disorder Clinic
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • La Jolla, California, United States, 78258
      • Coastal Neurological Medical Group Inc.
    • Reseda, California, United States, 91335
      • Neurosearch, Inc.
    • Ventura, California, United States, 93003
      • Neurosearch II, Inc.
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center of Boca Raton
    • Gainesville, Florida, United States, 32608
      • Neurology at Shands Medical Center
    • Jacksonville, Florida, United States, 32209
      • University of Florida at Jacksonville
    • Ormond Beach, Florida, United States, 32174
      • Neurology Associates of Ormond Beach
    • Port Charlotte, Florida, United States, 33952
      • Charlotte Neurological Services
    • Saint Petersburg, Florida, United States, 33701
      • Suncoast Neuroscience Associates, Inc.
    • Tampa, Florida, United States, 33606
      • USF Parkinson's Disease and Movement Disorders Center of Excellence
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Glenview, Illinois, United States, 60026
      • NorthShore University Health System
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Iowa Health Physicians
  • Maryland
    • Elkridge, Maryland, United States, 21075
      • Parkinson's & Movements Disorders Center of Maryland
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • Quest Research Institute
    • Southfield, Michigan, United States, 48034
      • Henry Ford Health System - Franklin Point
  • New York
    • Commack, New York, United States, 11725
      • Parkinson's Disease and Movement Disorders Center of Long Island
    • Kingston, New York, United States, 12401
      • Kingston Neurological Associates
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Neurological Institute, Cleveland Clinic
  • Texas
    • Dallas, Texas, United States, 75231
      • Neurology Specialist of Dallas P.A
    • Houston, Texas, United States, 77030
      • Parkinson's Disease and Movement Disorders Center, Baylor College of Medicine
    • San Antonio, Texas, United States, 78258
      • Neurology Associates, P.A.
    • Tyler, Texas, United States, 75701
      • East Texas Medical Center
  • Virginia
    • Virginia Beach, Virginia, United States, 23456
      • Sentara Neurological Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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
Placebo Comparator: Inactive substance	Drug: Placebo; Oral capsule, three times daily
Experimental: Trimethobenzamide (Tigan®)	Drug: Tigan®; Oral capsule, 300mg three times daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Nausea and/or Vomiting During the Initial Titration of Apokyn® at the Visit on Day 1	Day 1 (Period 1, Visit 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Nausea and/or Vomiting for Period 1		Days 1-28
Incidence of Nausea and/or Vomiting for Period 2		Days 29-56
Incidence of Nausea and/or Vomiting for Period 3		Days 57-84
Modified Index of Nausea, Vomiting and Retching (INVR) Scores - Total Experience Score for Period 1	The INVR is an 8-item, 5 point Likert-type measurement of the patient's perceived experience of nausea, vomiting and retching. Modified INVR scores collected once daily, rather than twice a day. INVR total score range from 0 to 32, with 32 indicative of the worst and 0 no symptom.	Days 1-28
Modified Index of Nausea, Vomiting and Retching (INVR) Scores - Total Experience Score for Period 2	The INVR is an 8-item, 5 point Likert-type measurement of the patient's perceived experience of nausea, vomiting and retching. Modified INVR scores collected once daily, rather than twice a day. INVR total score range from 0 to 32, with 32 indicative of the worst and 0 no symptom.	Days 29-56
Modified Index of Nausea, Vomiting and Retching (INVR) Scores - Total Experience Score for Period 3	The INVR is an 8-item, 5 point Likert-type measurement of the patient's perceived experience of nausea, vomiting and retching. Modified INVR scores collected once daily, rather than twice a day. INVR total score range from 0 to 32, with 32 indicative of the worst and 0 no symptom.	Days 57-84
Subject Global Evaluation of Randomized Study Medication for Period 1	The subject global evaluation of Tigan/placebo was completed by the subject at the visits in response to the question "Overall, how would you rate the study medication you received for nausea/vomiting?" Response choices were excellent, very good, good, fair, or poor.	Day 28 (Visit 3)
Subject Global Evaluation of Randomized Study Medication for Period 2	The subject global evaluation of Tigan/placebo was completed by the subject at the visits in response to the question "Overall, how would you rate the study medication you received for nausea/vomiting?" Response choices were excellent, very good, good, fair, or poor.	Day 56 (Visit 4)
Subject Global Evaluation of Randomized Study Medication for Period 3	The subject global evaluation of Tigan/placebo was completed by the subject at the visits in response to the question "Overall, how would you rate the study medication you received for nausea/vomiting?" Response choices were excellent, very good, good, fair, or poor.	Day 84 (Visit 5)
Median Time to 'on' for Visit 2/Period 1 Injection 1	Time to "on" (relief of immobility) was measured 20 minutes after administration of Apokyn and before discharge at the clinic; calculated as the difference between the recorded time of "on" and time of injection.	Day 1 (Visit 2)
Median Time to 'on' for Visit 2/Period 1 Injection 2	Time to "on" (relief of immobility) was measured 20 minutes after administration of Apokyn and before discharge at the clinic; calculated as the difference between the recorded time of "on" and time of injection.	Day 1 (Visit 2)
Median Time to 'on' for Visit 3/End of Period 1 Injection	Time to "on" (relief of immobility) was measured 20 minutes after administration of Apokyn and before discharge at the clinic; calculated as the difference between the recorded time of "on" and time of injection.	Day 28
Median Time to 'on' for Visit 4/End of Period 2 Injection	Time to "on" (relief of immobility) was measured 20 minutes after administration of Apokyn and before discharge at the clinic; calculated as the difference between the recorded time of "on" and time of injection.	Day 56 (Visit 4)
Median Time to 'on' for Visit 5/End of Period 3 Injection	Time to "on" (relief of immobility) was measured 20 minutes after administration of Apokyn and before discharge at the clinic; calculated as the difference between the recorded time of "on" and time of injection.	Day 84 (Visit 5)
Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 2, Pre Apokyn Dose, Period 1	Part 3 (Motor Examination) of the UPDRS contains 14 items designed to assess the severity of the cardinal motor findings (e.g., tremor, rigidity, bradykinesia, postural instability, etc.) in patients with Parkinson's disease. UPDRS motor score range from 0 to 56, with 56 indicative of the worst and 0 no disability.	Day 1 (Visit 2)
Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 3, Pre Apokyn Dose, Period 1	Part 3 (Motor Examination) of the UPDRS contains 14 items designed to assess the severity of the cardinal motor findings (e.g., tremor, rigidity, bradykinesia, postural instability, etc.) in patients with Parkinson's disease. UPDRS motor score range from 0 to 56, with 56 indicative of the worst and 0 no disability.	Day 28
Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 3, Post Apokyn Dose, Period 1	Part 3 (Motor Examination) of the UPDRS contains 14 items designed to assess the severity of the cardinal motor findings (e.g., tremor, rigidity, bradykinesia, postural instability, etc.) in patients with Parkinson's disease. UPDRS motor score range from 0 to 56, with 56 indicative of the worst and 0 no disability.	Day 28
Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 4, Pre Apokyn Dose, Period 2	Part 3 (Motor Examination) of the UPDRS contains 14 items designed to assess the severity of the cardinal motor findings (e.g., tremor, rigidity, bradykinesia, postural instability, etc.) in patients with Parkinson's disease. UPDRS motor score range from 0 to 56, with 56 indicative of the worst and 0 no disability.	Day 56 (Visit 4)
Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 4, Post Apokyn Dose, Period 2	Part 3 (Motor Examination) of the UPDRS contains 14 items designed to assess the severity of the cardinal motor findings (e.g., tremor, rigidity, bradykinesia, postural instability, etc.) in patients with Parkinson's disease. UPDRS motor score range from 0 to 56, with 56 indicative of the worst and 0 no disability.	Day 56 (Visit 4)
Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 5, Pre Apokyn Dose, Period 3	Part 3 (Motor Examination) of the UPDRS contains 14 items designed to assess the severity of the cardinal motor findings (e.g., tremor, rigidity, bradykinesia, postural instability, etc.) in patients with Parkinson's disease. UPDRS motor score range from 0 to 56, with 56 indicative of the worst and 0 no disability.	Day 84 (Visit 5)
Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 5, Post Apokyn Dose, Period 3	Part 3 (Motor Examination) of the UPDRS contains 14 items designed to assess the severity of the cardinal motor findings (e.g., tremor, rigidity, bradykinesia, postural instability, etc.) in patients with Parkinson's disease. UPDRS motor score range from 0 to 56, with 56 indicative of the worst and 0 no disability.	Day 56 (Visit 4)

Collaborators and Investigators

• Sponsor: Ipsen
• Collaborators: INC Research Limited

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: June 20, 2007
• First Submitted That Met QC Criteria: June 20, 2007
• First Posted (Estimate): June 21, 2007

Study Record Updates

• Last Update Posted (Actual): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 11, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Nausea; Vomiting; Parkinson's disease; Anti-emetic
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Digestive; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Nausea; Vomiting; Parkinson Disease
• Other Study ID Numbers: Y-47-52844-003; APO-4PD-01