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

Phase 4
Completed
Conditions
Parkinson's Disease
Interventions
Drug: Placebo
Registration Number
NCT00489255
Lead Sponsor
Ipsen
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
117
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Inactive substancePlacebo-
Trimethobenzamide (Tigan®)Tigan®-
Primary Outcome Measures
NameTimeMethod
Incidence of Nausea and/or Vomiting During the Initial Titration of Apokyn® at the Visit on Day 1Day 1 (Period 1, Visit 2)
Secondary Outcome Measures
NameTimeMethod
Incidence of Nausea and/or Vomiting for Period 2Days 29-56
Modified Index of Nausea, Vomiting and Retching (INVR) Scores - Total Experience Score for Period 3Days 57-84

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.

Median Time to 'on' for Visit 2/Period 1 Injection 1Day 1 (Visit 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.

Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 2, Pre Apokyn Dose, Period 1Day 1 (Visit 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.

Incidence of Nausea and/or Vomiting for Period 1Days 1-28
Incidence of Nausea and/or Vomiting for Period 3Days 57-84
Median Time to 'on' for Visit 2/Period 1 Injection 2Day 1 (Visit 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.

Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 4, Post Apokyn Dose, Period 2Day 56 (Visit 4)

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.

Subject Global Evaluation of Randomized Study Medication for Period 1Day 28 (Visit 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.

Median Time to 'on' for Visit 5/End of Period 3 InjectionDay 84 (Visit 5)

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.

Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 4, Pre Apokyn Dose, Period 2Day 56 (Visit 4)

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.

Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 5, Post Apokyn Dose, Period 3Day 56 (Visit 4)

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.

Subject Global Evaluation of Randomized Study Medication for Period 3Day 84 (Visit 5)

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.

Median Time to 'on' for Visit 4/End of Period 2 InjectionDay 56 (Visit 4)

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.

Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 3, Pre Apokyn Dose, Period 1Day 28

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.

Modified Index of Nausea, Vomiting and Retching (INVR) Scores - Total Experience Score for Period 1Days 1-28

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.

Modified Index of Nausea, Vomiting and Retching (INVR) Scores - Total Experience Score for Period 2Days 29-56

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.

Subject Global Evaluation of Randomized Study Medication for Period 2Day 56 (Visit 4)

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.

Median Time to 'on' for Visit 3/End of Period 1 InjectionDay 28

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.

Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 3, Post Apokyn Dose, Period 1Day 28

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.

Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor Section) for Visit 5, Pre Apokyn Dose, Period 3Day 84 (Visit 5)

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.

Trial Locations

Locations (27)

Neurological Institute, Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Parkinson's Disease and Movement Disorders Center of Long Island

🇺🇸

Commack, New York, United States

Kingston Neurological Associates

🇺🇸

Kingston, New York, United States

Neurosearch II, Inc.

🇺🇸

Ventura, California, United States

University of Florida at Jacksonville

🇺🇸

Jacksonville, Florida, United States

Emory University

🇺🇸

Atlanta, Georgia, United States

Neurosearch, Inc.

🇺🇸

Reseda, California, United States

Coastal Neurological Medical Group Inc.

🇺🇸

La Jolla, California, United States

Neurology Associates of Ormond Beach

🇺🇸

Ormond Beach, Florida, United States

Henry Ford Health System - Franklin Point

🇺🇸

Southfield, Michigan, United States

Neurology Specialist of Dallas P.A

🇺🇸

Dallas, Texas, United States

Parkinson's Disease and Movement Disorders Center, Baylor College of Medicine

🇺🇸

Houston, Texas, United States

Parkinson's Disease and Movement Disorders Center of Boca Raton

🇺🇸

Boca Raton, Florida, United States

Neurology at Shands Medical Center

🇺🇸

Gainesville, Florida, United States

Charlotte Neurological Services

🇺🇸

Port Charlotte, Florida, United States

Suncoast Neuroscience Associates, Inc.

🇺🇸

Saint Petersburg, Florida, United States

USF Parkinson's Disease and Movement Disorders Center of Excellence

🇺🇸

Tampa, Florida, United States

Quest Research Institute

🇺🇸

Bingham Farms, Michigan, United States

Parkinson's & Movements Disorders Center of Maryland

🇺🇸

Elkridge, Maryland, United States

NorthShore University Health System

🇺🇸

Glenview, Illinois, United States

Iowa Health Physicians

🇺🇸

Des Moines, Iowa, United States

Sentara Neurological Associates

🇺🇸

Virginia Beach, Virginia, United States

Barrow Neurological Movement Disorder Clinic

🇺🇸

Phoenix, Arizona, United States

Mayo Clinic

🇺🇸

Scottsdale, Arizona, United States

Raleigh Neurology Associates

🇺🇸

Raleigh, North Carolina, United States

Neurology Associates, P.A.

🇺🇸

San Antonio, Texas, United States

East Texas Medical Center

🇺🇸

Tyler, Texas, United States

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