Apokyn for Motor IMProvement of Morning AKinesia Trial (AM IMPAKT) (AM IMPAKT)
Delayed Levadopa Onset
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 4, Open-Label, Efficacy and Safety Study of Apokyn® for Rapid and Reliable Improvement of Motor Symptoms in Parkinson Disease Subjects With Delayed Onset of L-Dopa Action|
- Change From Baseline in Average Daily "Time to on" ("TTO") by Subject Diary. [ Time Frame: L-Dopa Baseline Days 1-7 and APOKYN Treatment Days 1-7 ] [ Designated as safety issue: No ]Patients will record daily "time to on" or "TTO" following their regularly scheduled first L-Dopa dose in the baseline period for 7 consecutive days. Following initiation on Apokyn therapy, patients will inject Apokyn at their regularly scheduled L-Dopa time (L-Dopa dosing will be delayed by 40 minutes following Apokyn injection) and record "time to on" or "TTO" from the injection. "Time to on" for both periods will be recorded in a standardized subject diary. Daily "TTO" for the baseline period will be averaged for each subject and compared to the daily "TTO" for the same subject during the treatment period to assess APOKYN's effect on "TTO".
- Change From Baseline in Gastric Emptying Time [ Time Frame: L-Dopa Baseline Days 1-7 and APOKYN Treatment Days 1-8 ] [ Designated as safety issue: No ]A sub-group of subjects from 1 study site that have symptoms of gastroparesis were admitted to the clinic on 2 occasions to undergo gastroparesis procedures and assessments (once at the conclusion of the baseline L-dopa period and once at the conclusion of the APOKYN treatment period). Note, to do the second gastroparesis assessment, this sub-group of subjects had an extension for one extra day beyond the designated 7 day APOKYN treatment period (i.e., it will be 8 days) in order to keep the 7 day diary recording outpatient scope of work the same as the rest of the subjects in the study. The second inpatient period was also considered the end-of-study visit for this sub group.
|Study Start Date:||December 2012|
|Study Completion Date:||April 2014|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
APOKYN (apomorphine hydrochloride injection) is used as needed to treat off-episode motor symptoms, such as muscle stiffness, slow movements, and difficulty starting movements, in people with advanced Parkinson's disease (PD).
In the study, subjects will complete an L-Dopa Baseline Period in which they record daily "time to on" following their regularly scheduled L-Dopa morning dose for 7 days. At the end of the baseline period, patients will start trimethobenzamide therapy during a minimum 3-Day Anti-Emetic Pretreatment Period. Patients determined to remain eligible at the end of the required Anti-Emetic Pretreatmetn Period will be initiated on APOKYN therapy by an investigator. Once the appropriate dose is identified by a study investigator, patients will inject APOKYN at their regularly scheduled levodopa morning dose time (levodopa will be delayed by 40 minutes) daily during a 7-day APOKYN Treatment Period and record "time to on" following the APOKYN injection.
Apokyn will be titrated to an optimum dose which reproduces 90% of the subjects' "best on" UPDRS score during the Initiation Period. During the APOKYN Treatment Period, subjects will inject the dose identified in the initiation period once daily at the time of their normal scheduled L-Dopa dose (L-Dopa will be delayed by 40 minutes).
Other Name: apomorphine hydrochloride injectionDrug: L-dopa
Subjects on a stable L-Dopa regimen will be entered into the study. For the L-Dopa Baseline Period through the Initiation Period, subjects will continue their normal L-Dopa dosing regimen. During the APOKYN Treatment Period, subjects will replace their normally scheduled first morning L-Dopa dose with an APOKYN injection, and then administer their normal first morning L-Dopa dose 40 minutes later.
Other Name: Levodopa, Levodopa/Carbidopa, Sinemet, Sinemet CR, ParcopaDrug: Trimethobenzamide
Following the L-Dopa Baseline Period, subjects will initiate trimethobenzamide treatment TID for a minimum of 3 days during a Anti-Emetic Pretreatment Period. Subjects will continue trimethobenzamide therapy TID through the duratoin of the APOKYN Initiation Period and APOKYN Treatment Period.
Other Name: Tigan
This Phase IV, Open-Label, Efficacy and Safety Study of APOKYN® is intended to assess the effect of APOKYN treatment in rapid and reliable improvement of motor symptoms in PD subjects suffering from delayed or unreliable onset of L-dopa action. The study will also include a sub-group of 8 subjects to evaluate their gastroparesis and assess their gastric empty with other measures to explore if APOKYN has any influence on gastric empty rather than just bypassing the stomach with a subcutaneous route of administration.
The primary objective of this study is to assess the effect of APOKYN treatment in rapid and reliable improvement of motor symptoms in PD subjects suffering from delayed or unreliable onset of L-dopa action (defined below). APOKYN treatment will also be assessed in a sub-group of PD subjects suffering from gastroparesis and delayed onset of L-dopa action.
Delayed or unreliable onset to L-dopa for the study population is defined as impaired motor function (tremor, bradykinesia, rigidity, and/or postural instability) persisting for a minimum of 45 minutes after taking a dose of L-dopa because of its delay in onset of action. The impaired motor function resulting from delay in L-dopa onset is referred to as "delayed ON" and when it occurs upon awakening is referred to as "morning akinesia."
This is a multicenter, multiple-treatment, open-label, outpatient study to evaluate the efficacy and safety of APOKYN in PD subjects with delayed onset of L dopa action. The study will have:
- Screening - 1-5 days (Visit 1);
- Baseline L-Dopa Period - 7 days, continuation of L dopa treatment;
- Antiemetic Treatment Period - 3-days; initiation of trimethobenzamide 300 mg tid orally;
- APOKYN Initiation/optimum dose identification Period (Visit 2)- variable, not more than 11 days;
- APOKYN Treatment Period - 7 days, immediately upon identification of optimum dose;
- Study Discharge (Visit 3)- within 2 days of completion of the APOKYN treatment period.
A sub-group of subjects (n=8) from 1 study site that have symptoms of gastroparesis will be admitted to the clinic on 2 occasions to undergo gastroparesis procedures and assessments (once at the conclusion of the baseline L-dopa period and once at the conclusion of the APOKYN treatment period). Note, to do the second gastroparesis assessment, this sub-group of subjects will have an extension for one extra day beyond the designated 7 day APOKYN treatment period (i.e., it will be 8 days) in order to keep the 7 day diary recording outpatient scope of work the same as the rest of the subjects in the study. The second inpatient period will be also considered the end-of-study visit for this sub group.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01770145
|United States, California|
|Keck School of Medicine|
|Los Angeles, California, United States, 90033|
|Reseda, California, United States, 91335|
|United States, District of Columbia|
|Washington DC, District of Columbia, United States, 20007|
|United States, Florida|
|Parkinson's Disease and Movement Disorders Center of Boca Raton|
|Boca Raton, Florida, United States, 33486|
|United States, Illinois|
|Rush University Medical Center|
|Chicago, Illinois, United States, 60612|
|United States, Michigan|
|Henry Ford West Bloomfield Hospital|
|Bloomfield Hills, Michigan, United States, 48322|
|United States, New York|
|Parkinson's Disease and Movement Disorders Center of New York|
|Commack, New York, United States, 11725|
|United States, Ohio|
|University of Cincinnati Academic Health Center|
|Cincinnati, Ohio, United States, 45267|
|University Hospitals Case Medical Center|
|Cleveland, Ohio, United States, 44106|
|United States, Oklahoma|
|The Movement Disorder Clinic of Oklahoma|
|Tulsa, Oklahoma, United States, 74136|
|United States, Texas|
|University of Texas Health Science Center, Houston, Department of Neurology|
|Houston, Texas, United States, 77030|
|Center for Neurological Care and Research|
|San Antonio, Texas, United States, 78240|
|Principal Investigator:||Stuart H. Isaacson, MD||Parkinson's Disease and Movement Disorders Center of Boca Raton|