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

Parkinson's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00489255
• Other study ID #: Y-47-52844-003
• Secondary ID: APO-4PD-01
• Status: Completed
• Phase: Phase 4
• Start date: May 2007
• Est. completion date: March 2012

Study information

• Verified date: January 2019
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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®

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 117
• Est. completion date: March 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Nausea
• Parkinson Disease
• Parkinson's Disease
• Vomiting

Intervention

Drug:
• Tigan®
Oral capsule, 300mg three times daily
• Placebo
Oral capsule, three times daily

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Quest Research Institute	Bingham Farms	Michigan
United States	Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida
United States	Neurological Institute, Cleveland Clinic	Cleveland	Ohio
United States	Parkinson's Disease and Movement Disorders Center of Long Island	Commack	New York
United States	Neurology Specialist of Dallas P.A	Dallas	Texas
United States	Iowa Health Physicians	Des Moines	Iowa
United States	Parkinson's & Movements Disorders Center of Maryland	Elkridge	Maryland
United States	Neurology at Shands Medical Center	Gainesville	Florida
United States	NorthShore University Health System	Glenview	Illinois
United States	Parkinson's Disease and Movement Disorders Center, Baylor College of Medicine	Houston	Texas
United States	University of Florida at Jacksonville	Jacksonville	Florida
United States	Kingston Neurological Associates	Kingston	New York
United States	Coastal Neurological Medical Group Inc.	La Jolla	California
United States	Neurology Associates of Ormond Beach	Ormond Beach	Florida
United States	Barrow Neurological Movement Disorder Clinic	Phoenix	Arizona
United States	Charlotte Neurological Services	Port Charlotte	Florida
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	Neurosearch, Inc.	Reseda	California
United States	Suncoast Neuroscience Associates, Inc.	Saint Petersburg	Florida
United States	Neurology Associates, P.A.	San Antonio	Texas
United States	Mayo Clinic	Scottsdale	Arizona
United States	Henry Ford Health System - Franklin Point	Southfield	Michigan
United States	USF Parkinson's Disease and Movement Disorders Center of Excellence	Tampa	Florida
United States	East Texas Medical Center	Tyler	Texas
United States	Neurosearch II, Inc.	Ventura	California
United States	Sentara Neurological Associates	Virginia Beach	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Ipsen	INC Research Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence of Nausea and/or Vomiting for Period 1		Days 1-28
Secondary	Incidence of Nausea and/or Vomiting for Period 2		Days 29-56
Secondary	Incidence of Nausea and/or Vomiting for Period 3		Days 57-84
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)