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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Tigan®
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trimethobenzamide (Tigan®)<br> | Drug: Tigan®<br>* Oral capsule, 300mg three times daily<br>|
| Placebo Comparator: Inactive substance<br> | Drug: Placebo<br>* Oral capsule, three times daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Anti-emetic, Nausea, Vomiting