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

M

MDD US Operations

Status and phase

Completed
Phase 4

Conditions

Hypomobility
Parkinson's Disease
Akinesia
Motor Symptoms
Delayed Levodopa Onset

Treatments

Drug: APOKYN
Drug: L-dopa
Drug: Trimethobenzamide

Study type

Interventional

Funder types

Industry

Identifiers

NCT01770145
USWM-AP1-4001

Details and patient eligibility

About

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.

Full 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.

Enrollment

127 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

127 participants in 1 patient group

APOKYN
Experimental group
Description:
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.
Treatment:
Drug: Trimethobenzamide
Drug: L-dopa
Drug: APOKYN

Trial contacts and locations

12

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Data sourced from clinicaltrials.gov

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