A Study That Compares the Extent to Which Apomorphine Becomes Available in the Body After Taking Either an Investigational Drug Containing Apomorphine or Apomorphine That is Injected Under the Skin in People With PD Complicated by "OFF" Episodes

NCT ID: NCT03292016

Last Updated: 2020-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-22
• Study Completion Date: 2019-03-05

Brief Summary

A study that compares the extent to which apomorphine becomes available in the body after taking either an investigational drug containing apomorphine or apomorphine that is injected under the skin in people with PD complicated by "OFF" episodes.

Detailed Description

This multi-center study will aim to evaluate the pharmacokinetics (PK) and comparative bioavailability of a single dose of APL-130277 sublingual thin film with subcutaneous (s.c.) APO-go® and s.c. APOKYN® in subjects with Parkinson's disease (PD). The dose of APOKYN® (≤ 5 mg) will be based on the subjects' current prescribed dose. The study is designed as an open-label, randomized, three-way crossover. Subjects will receive all three treatment arms with a minimum 1-day wash-out between each visit (excluding the screening visit) and will be randomly assigned to one of the six sequences

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

APL-130277, sublingual thin film

APL-130277, sublingual thin film, once daily

Group Type: EXPERIMENTAL

APL-130277

Intervention Type: DRUG

APL-130277 sublingual thin film

Subcutaneous APO-go

Subcutaneous APO-go, once daily

Group Type: ACTIVE_COMPARATOR

APO-go

Intervention Type: DRUG

Subcutaneous APO-go

Subcutaneous APOKYN

Subcutaneous APOKYN, once daily

Group Type: ACTIVE_COMPARATOR

Apokyn

Intervention Type: DRUG

Subcutaneous APOKYN

Interventions

APL-130277

APL-130277 sublingual thin film

Intervention Type: DRUG

APO-go

Subcutaneous APO-go

Intervention Type: DRUG

Apokyn

Subcutaneous APOKYN

Intervention Type: DRUG

Other Intervention Names

amomorphine; amomorphine; amomorphine

Eligibility Criteria

Inclusion Criteria

1. Male or female ≥ 18 years of age.

2. Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria (excluding the "more than one affected relative" criterion).

3. Clinically meaningful response to Levodopa (L-Dopa) with well-defined "OFF" episodes, as determined by the Investigator.

4. Receiving APOKYN® of ≤ 5 mg per dose for at least 4 weeks before the Screening Visit.

5. Receiving stable doses of L-Dopa/carbidopa (immediate or sustained release) administered at least 4 times per day OR Rytary™ administered 3 times per day, for at least 4 weeks before the Screening Visit. Adjunctive PD medication regimens must be maintained at a stable dose for at least 4 weeks prior to the Screening Visit with the exception that MAOB inhibitors must be maintained at a stable level for at least 8 weeks prior to the Screening Visit.

6. No planned medication change(s) or surgical intervention anticipated during the course of study.

7. Patients must experience a well-defined "OFF" episode in the morning if they do not take their morning PD medications on schedule, and must be willing to delay morning doses on the 3 study dosing days

8. Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.

9. Mini-Mental State Examination (MMSE) score > 23.

10. If female and of childbearing potential, must agree to use one of the following methods of birth control:

• Oral contraceptive;
• 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).

11. Male patients must be either surgically sterile, agree to be sexually abstinent or use a barrier method of birth control (e.g., condom) or maintain a monogamous relationship with a person who is not of child-bearing potential from first study drug administration until 30days after final drug administration.

12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study.

13. Able to understand the consent form, and to provide written informed consent

Exclusion Criteria

1. Atypical or secondary parkinsonism.

2. Previous treatment with any of the following: continuous subcutaneous (s.c.) apomorphine infusion; or Duodopa/Duopa.

3. Contraindications to APO-go® or APOKYN® or hypersensitivity to apomorphine hydrochloride or any marcrolide antibiotic or any of the ingredients APO-go® or APOKYN® (notably sodium metabisulfite).

4. Female who is pregnant or lactating.

5. Participation in a clinical trial within 30 days prior to the Screening Visit.

6. Receipt of any investigational (ie, unapproved) medication within 30 days prior to the Screening Visit.

7. Any selective 5HT3 antagonists (ie, ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine and clozapine) or dopamine depleting agents within 30 days prior to the Screening Visit.

8. Drug or alcohol dependency in the past 12 months.

9. History of malignant melanoma.

10. Clinically significant medical, surgical, or laboratory abnormality in the opinion of the Investigator.

11. Major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis, or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.

12. History of clinically significant hallucinations during the past 6 months.

13. History of clinically significant impulse control disorder(s).

14. Dementia that precludes providing informed consent or would interfere with participation in the study.

15. Current suicidal ideation within one year prior to the Screening Visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) or attempted suicide within the last 5 years.

16. Donation of blood plasma in the 30 days prior to first dosing.

17. Cankers or mouth sores within 30 days prior to the Screening Visit, or other clinically significant oral pathology in the opinion of the Investigator. The Investigator should follow-up with an appropriate specialist on any finding, if indicated, before enrolling a patient into the study.

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

Sponsors

Sumitomo Pharma America, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

CNS Mecdical Director

Role: STUDY_CHAIR

Sunovion Pharmacetuicals Inc.

Locations

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, United States

Parkinson's Disese Treatment Center of SW Florida

Port Charlotte, Florida, United States

QUEST Research Institute

Farmington Hills, Michigan, United States

Countries

United States

References

Agbo F, Isaacson SH, Gil R, Chiu YY, Brantley SJ, Bhargava P, Navia B. Pharmacokinetics and Comparative Bioavailability of Apomorphine Sublingual Film and Subcutaneous Apomorphine Formulations in Patients with Parkinson's Disease and "OFF" Episodes: Results of a Randomized, Three-Way Crossover, Open-Label Study. Neurol Ther. 2021 Dec;10(2):693-709. doi: 10.1007/s40120-021-00251-6. Epub 2021 May 15.

Reference Type: DERIVED

PMID: 33991326 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CTH-203

Identifier Type: -

Identifier Source: org_study_id