Apokyn for Motor IMProvement of Morning AKinesia Trial (AM IMPAKT)

NCT01770145 | Completed Phase 4 Results

• 1 other identifier: USWM-AP1-4001
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 12

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.

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Average Daily "Time to on" ("TTO") by Subject Diary.

  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".

  L-Dopa Baseline Days 1-7 and APOKYN Treatment Days 1-7

Secondary Outcomes (1)

• Change From Baseline in Gastric Emptying Time

  L-Dopa Baseline Days 1-7 and APOKYN Treatment Days 1-8

Study Arms (1)

APOKYN

EXPERIMENTAL

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 Pretreatment 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.

Drug: APOKYN; Drug: L-dopa; Drug: Trimethobenzamide

Interventions

APOKYN DRUG

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).

Also known as: apomorphine hydrochloride injection

APOKYN

L-dopa DRUG

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.

Also known as: Levodopa, Levodopa/Carbidopa, Sinemet, Sinemet CR, Parcopa

APOKYN

Trimethobenzamide DRUG

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 duration of the APOKYN Initiation Period and APOKYN Treatment Period.

Also known as: Tigan

APOKYN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥18 years of age.
• Idiopathic PD.
• Not currently taking APOKYN and, if previously prescribed APOKYN, did not discontinue therapy due to intolerable side effects/safety reasons.
• 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.
• 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).
• Able to adequately differentiate between and describe variations in "on" and "off" states in the opinion of the Investigator.
• I to III Modified Hoehn and Yahr stage in the "on" state (Appendix B).
• Be seeking treatment for early morning akinesia.
• 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;

You may not qualify if:

• Changes in L-dopa dosing regimen 4 weeks before the screening visit.
• Female who is pregnant or lactating.
• Contraindications to APOKYN or hypersensitive to apomorphine hydrochloride or any of the ingredients of APOKYN (notably sodium metabisulfite).
• Participation in any other clinical trial within 14 days of the screening visit.
• Receipt of any investigational (i.e., unapproved) medication within 30 days of the screening visit.
• 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).
• Currently taking medications for treatment of gastroparesis (e.g., erythromycin, cisapride, metoclopramide).
• Malignant melanoma or a history of previously treated malignant melanoma within 5 years.
• Serious medical illness including, but not limited to:
• Liver disease;
• Kidney problems; and
• Heart problems.
• 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.
• Lack of compliance and follow-up.
• 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.

Sponsors & Collaborators

• MDD US Operations, LLC a subsidiary of Supernus Pharmaceuticals: lead

Study Sites (12)

Keck School of Medicine

Los Angeles, California, 90033, United States

Location

Neurosearch, Inc.

Reseda, California, 91335, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Henry Ford West Bloomfield Hospital

Bloomfield Hills, Michigan, 48322, United States

Location

Parkinson's Disease and Movement Disorders Center of New York

Commack, New York, 11725, United States

Location

University of Cincinnati Academic Health Center

Cincinnati, Ohio, 45267, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, 74136, United States

Location

University of Texas Health Science Center, Houston, Department of Neurology

Houston, Texas, 77030, United States

Location

Center for Neurological Care and Research

San Antonio, Texas, 78240, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Apomorphine; Levodopa; Carbidopa; carbidopa, levodopa drug combination; trimethobenzamide

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Aporphines; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings; Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine; Methyldopa; Hydrazines

Limitations and Caveats

Full analysis set (n=88) included patients who completed 5/7 days of diary entries in APOKYN treatment period. The gastroparesis sub-study to assess prevalence and severity of gastroparesis was not analyzed because too few subjects were enrolled.

Results Point of Contact

• Title: Regulatory Associate, Clinical Operations
• Organization: US WorldMeds

rgerlach@usworldmeds.com

5028158130

Study Officials

• Gianpiera H. Ceresoli-Borroni, PhD

  Supernus Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2013
• First Posted: January 17, 2013
• Study Start: December 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: August 14, 2023
• Results First Posted: September 7, 2015

Record last verified: 2017-10

Locations

US (12)