Clinical trial NCT01770145: Apokyn for Motor IMProvement of Morning AKinesia Trial (AM IMPAKT)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson's Disease
Motor Symptoms
Akinesia
Hypomobility
Delayed Levodopa Onset
Keywords: Motor symptoms
Parkinson's Disease
Delayed Onset
Akinesia
Hypomobility
Unified Parkinson Disease Rating Scale (UPDRS) motor scores
Dopamine agonist
Apomorphine
Apokyn
Levodopa
Lead sponsor: Supernus Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2013-01-17
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is designed to assess the effect of APOKYN treatment in rapid and reliable improvement of motor symptoms in Parkinson's disease (PD) subjects suffering from delayed or unreliable onset of levodopa (L-dopa) action.

Detailed description: 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."

Main Study:

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.

Gastroparesis Sub-Study:

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female ≥18 years of age.
2. Idiopathic PD.
3. Not currently taking APOKYN and, if previously prescribed APOKYN, did not discontinue therapy due to intolerable side effects/safety reasons.
4. Prescribed L-dopa therapy at a steady maintenance dose, representing an optimal treatment regimen in the opinion of the Investigator, for at least 4 weeks before study participation.
5. Minimum subject-reported time to turn "on" (TTO) in the early morning (time to end akinetic/ bradykinetic state resulting from delay in L-dopa onset of action) of 45 minutes after the first morning L-dopa dose for a minimum of 3 days/week (as determined with the subject diary at Visit 2).
6. Able to adequately differentiate between and describe variations in "on" and "off" states in the opinion of the Investigator.
7. I to III Modified Hoehn and Yahr stage in the "on" state (Appendix B).
8. Be seeking treatment for early morning akinesia.
9. If female and of childbearing potential, must agree to use one of the following methods of birth control:

   * Oral contraceptive;
   * Patch;
   * Barrier (diaphragm, sponge or condom) plus spermicidal preparations;
   * Intrauterine contraceptive system;
   * Levonorgestrel implant;
   * Medroxyprogesterone acetate contraceptive injection;
   * Complete abstinence from sexual intercourse;
   * Hormonal vaginal contraceptive ring; or
   * Surgical sterilization or partner sterile (must have documented proof).
10. Access to a live-in caregiver, if needed.
11. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study.
12. Able to verbalize understanding of the consent form, able to provide written informed consent.

    The following must be present for inclusion in the single site gastroparesis sub-study:
13. Have symptoms of gastroparesis.
14. Have improvement of at least one Modified Hoehn and Yahr stage from "off" to "on."
15. Currently seeking treatment for delayed L-dopa onset.
16. Have no allergy to eggs.

Exclusion Criteria:

1. Changes in L-dopa dosing regimen 4 weeks before the screening visit.
2. Female who is pregnant or lactating.
3. Contraindications to APOKYN or hypersensitive to apomorphine hydrochloride or any of the ingredients of APOKYN (notably sodium metabisulfite).
4. Participation in any other clinical trial within 14 days of the screening visit.
5. Receipt of any investigational (i.e., unapproved) medication within 30 days of the screening visit.
6. Currently taking, or likely to need to take at any time during the course of the study, any 5HT3 antagonist (i.e., ondansetron, granisetron, dolasetron, palonosetron, alosetron).
7. Currently taking medications for treatment of gastroparesis (e.g., erythromycin, cisapride, metoclopramide).
8. Malignant melanoma or a history of previously treated malignant melanoma within 5 years.
9. Serious medical illness including, but not limited to:

   * Liver disease;
   * Kidney problems; and
   * Heart problems.
10. Psychiatric disorder, including but not limited to dementia or any disorder that, in the opinion of the Investigator requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
11. Lack of compliance and follow-up.
12. Any other condition, current therapy, or prior therapy (within 30 days of the screening visit), which, in the opinion of the Investigator, would make the subject unsuitable for the study.

Primary outcomes:
measure: Change From Baseline in Average Daily "Time to on" ("TTO") by Subject Diary.
timeFrame: L-Dopa Baseline Days 1-7 and APOKYN Treatment Days 1-7
Secondary outcomes:
measure: Change From Baseline in Gastric Emptying Time
timeFrame: L-Dopa Baseline Days 1-7 and APOKYN Treatment Days 1-8
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Keck School of Medicine
state: California
city: Reseda
country: United States
facility: Neurosearch, Inc.
state: California
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Bloomfield Hills
country: United States
facility: Henry Ford West Bloomfield Hospital
state: Michigan
city: Commack
country: United States
facility: Parkinson's Disease and Movement Disorders Center of New York
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Academic Health Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Tulsa
country: United States
facility: The Movement Disorder Clinic of Oklahoma
state: Oklahoma
city: Houston
country: United States
facility: University of Texas Health Science Center, Houston, Department of Neurology
state: Texas
city: San Antonio
country: United States
facility: Center for Neurological Care and Research
state: Texas
Study officials:
affiliation: Supernus Pharmaceuticals
name: Gianpiera H. Ceresoli-Borroni, PhD
role: STUDY_DIRECTOR
References: