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

This study has been completed.
Sponsor:
Collaborator:
INC Research Limited
Information provided by (Responsible Party):
Ipsen
ClinicalTrials.gov Identifier:
NCT00489255
First received: June 20, 2007
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

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®


Condition Intervention Phase
Parkinson's Disease
Drug: Tigan®
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: 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

Resource links provided by NLM:


Further study details as provided by Ipsen:

Primary Outcome Measures:
  • Incidence of Nausea and/or Vomiting During the Initial Titration of Apokyn® at the Visit on Day 1 [ Time Frame: Day 1 (Period 1, Visit 2) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of Nausea and/or Vomiting for Period 1 [ Time Frame: Days 1-28 ] [ Designated as safety issue: Yes ]
  • Incidence of Nausea and/or Vomiting for Period 2 [ Time Frame: Days 29-56 ] [ Designated as safety issue: Yes ]
  • Incidence of Nausea and/or Vomiting for Period 3 [ Time Frame: Days 57-84 ] [ Designated as safety issue: Yes ]
  • Modified Index of Nausea, Vomiting and Retching (INVR) Scores - Total Experience Score for Period 1 [ Time Frame: Days 1-28 ] [ Designated as safety issue: Yes ]
    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 2 [ Time Frame: Days 29-56 ] [ Designated as safety issue: Yes ]
    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 3 [ Time Frame: Days 57-84 ] [ Designated as safety issue: Yes ]
    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 1 [ Time Frame: Day 28 (Visit 3) ] [ Designated as safety issue: No ]
    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.

  • Subject Global Evaluation of Randomized Study Medication for Period 2 [ Time Frame: Day 56 (Visit 4) ] [ Designated as safety issue: No ]
    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.

  • Subject Global Evaluation of Randomized Study Medication for Period 3 [ Time Frame: Day 84 (Visit 5) ] [ Designated as safety issue: No ]
    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 2/Period 1 Injection 1 [ Time Frame: Day 1 (Visit 2) ] [ Designated as safety issue: No ]
    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.

  • Median Time to 'on' for Visit 2/Period 1 Injection 2 [ Time Frame: Day 1 (Visit 2) ] [ Designated as safety issue: No ]
    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.

  • Median Time to 'on' for Visit 3/End of Period 1 Injection [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    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.

  • Median Time to 'on' for Visit 4/End of Period 2 Injection [ Time Frame: Day 56 (Visit 4) ] [ Designated as safety issue: No ]
    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.

  • Median Time to 'on' for Visit 5/End of Period 3 Injection [ Time Frame: Day 84 (Visit 5) ] [ Designated as safety issue: No ]
    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 1 [ Time Frame: Day 1 (Visit 2) ] [ Designated as safety issue: No ]
    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 3, Pre Apokyn Dose, Period 1 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    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 3, Post Apokyn Dose, Period 1 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    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 4, Pre Apokyn Dose, Period 2 [ Time Frame: Day 56 (Visit 4) ] [ Designated as safety issue: No ]
    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 4, Post Apokyn Dose, Period 2 [ Time Frame: Day 56 (Visit 4) ] [ Designated as safety issue: No ]
    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 3 [ Time Frame: Day 84 (Visit 5) ] [ Designated as safety issue: No ]
    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 3 [ Time Frame: Day 56 (Visit 4) ] [ Designated as safety issue: No ]
    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.


Enrollment: 117
Study Start Date: May 2007
Study Completion Date: March 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trimethobenzamide (Tigan®) Drug: Tigan®
Oral capsule, 300mg three times daily
Placebo Comparator: Inactive substance Drug: Placebo
Oral capsule, three times daily

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00489255

  Show 27 Study Locations
Sponsors and Collaborators
Ipsen
INC Research Limited
Investigators
Study Director: Stephen Revell, MD Ipsen
  More Information

No publications provided

Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT00489255     History of Changes
Other Study ID Numbers: Y-47-52844-003, APO-4PD-01
Study First Received: June 20, 2007
Results First Received: December 24, 2012
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Ipsen:
Parkinson's disease
Anti-emetic
Nausea
Vomiting

Additional relevant MeSH terms:
Nausea
Parkinson Disease
Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Trimethobenzamide
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents

ClinicalTrials.gov processed this record on August 19, 2014