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

NCT ID: NCT01770145

Last Updated: 2023-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2014-04-30

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.

Conditions

Parkinson's Disease; Motor Symptoms; Akinesia; Hypomobility; Delayed Levodopa Onset

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

APOKYN

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.

Group Type: EXPERIMENTAL

APOKYN

Intervention Type: 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).

L-dopa

Intervention Type: 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.

Trimethobenzamide

Intervention Type: 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.

Interventions

APOKYN

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).

Intervention Type: DRUG

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.

Intervention Type: DRUG

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 duration of the APOKYN Initiation Period and APOKYN Treatment Period.

Intervention Type: DRUG

Other Intervention Names

apomorphine hydrochloride injection; Levodopa, Levodopa/Carbidopa, Sinemet, Sinemet CR, Parcopa; Tigan

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MDD US Operations, LLC a subsidiary of Supernus Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gianpiera H. Ceresoli-Borroni, PhD

Role: STUDY_DIRECTOR

Supernus Pharmaceuticals

Locations

Keck School of Medicine

Los Angeles, California, United States

Neurosearch, Inc.

Reseda, California, United States

Georgetown University

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

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

Henry Ford West Bloomfield Hospital

Bloomfield Hills, Michigan, United States

Parkinson's Disease and Movement Disorders Center of New York

Commack, New York, United States

University of Cincinnati Academic Health Center

Cincinnati, Ohio, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, United States

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

Houston, Texas, United States

Center for Neurological Care and Research

San Antonio, Texas, United States

Countries

United States

Other Identifiers

USWM-AP1-4001

Identifier Type: -

Identifier Source: org_study_id