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

NCT03292016 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CTH-203
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

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.

Conditions

Parkinson Disease

Keywords

Off Episodes; Parkinson Disease

Outcome Measures

Primary Outcomes (11)

• Maximum Observed Plasma Concentration (Cmax)

  Dose normalized maximum observed plasma concentration (Cmax)

  Day 1

• Observed Time of the Maximum Concentration (Tmax)

  Time from dosing to Cmax, observed by inspection of individual subject plots of plasma concentration versus time.

  Day 1

• Area Under the Concentration- Time Curve (AUC Last)

  area under the concentration-time curve from time zero to the last measurable plasma concentration-time curve using the linear up log down trapezoidal rule.

  Day 1

• Area Under the Concentration- Time Curve (AUC Inf)

  area under the concentration-time curve from time zero extrapolated to infinity using the linear up log down trapezoidal rule.

  Day 1

• Mean Residence Time (MRT)

  Mean residence time during one dosing interval calculated using the following equation: MRT = AUMCinf/AUC inf. AUMCinf is the area under the first moment (time.plasma concentration vs. time) curve.

  Day 1

• Metabolite/Parent (M/P) Drug Concentration Ratio -Cmax

  Metabolite (apomorphine sulfate) to Parent exposure ratio, Cmax, corrected for molecular weight differences.

  Day 1

• Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F)

  Apparent total clearance of the drug from plasma extravascular administration, calculated as Dose/AUCinf.

  Day 1

• Apparent Volume of Distribution After Non-intravenous Administration (V/F)

  Apparent volume of distribution after extravascular administration, calculated as Dose/(AUCinf \* λz).

  Day 1

• Terminal-phase Half-life (t½)

  Terminal phase half-life, as calculated by the following equation: t½ = ln(2)/λz.

  Day 1

• Terminal-phase Rate Constant ( λz)

  Apparent terminal elimination rate constant, determined by log linear regression of the plasma concentration versus time data that was judged to be in the log-linear elimination phase. At least 3 data points in the terminal phase will be used in the determination of the rate constant.

  Day 1

• Metabolite/Parent (M/P) Drug Concentration Ratio -AUC Last

  Metabolite (apomorphine sulfate) to Parent exposure ratio, AUClast, corrected for molecular weight differences.

  Day 1

Study Arms (3)

APL-130277, sublingual thin film

EXPERIMENTAL

APL-130277, sublingual thin film, once daily

Drug: APL-130277

Subcutaneous APO-go

ACTIVE COMPARATOR

Subcutaneous APO-go, once daily

Drug: APO-go

Subcutaneous APOKYN

ACTIVE COMPARATOR

Subcutaneous APOKYN, once daily

Drug: Apokyn

Interventions

APL-130277 DRUG

APL-130277 sublingual thin film

Also known as: amomorphine

APL-130277, sublingual thin film

APO-go DRUG

Subcutaneous APO-go

Also known as: amomorphine

Subcutaneous APO-go

Apokyn DRUG

Subcutaneous APOKYN

Also known as: amomorphine

Subcutaneous 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.
• Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria (excluding the "more than one affected relative" criterion).
• Clinically meaningful response to Levodopa (L-Dopa) with well-defined "OFF" episodes, as determined by the Investigator.
• Receiving APOKYN® of ≤ 5 mg per dose for at least 4 weeks before the Screening Visit.
• 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.
• No planned medication change(s) or surgical intervention anticipated during the course of study.
• 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
• Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
• Mini-Mental State Examination (MMSE) score \> 23.
• 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;

You may not qualify if:

• Atypical or secondary parkinsonism.
• Previous treatment with any of the following: continuous subcutaneous (s.c.) apomorphine infusion; or Duodopa/Duopa.
• 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).
• Female who is pregnant or lactating.
• Participation in a clinical trial within 30 days prior to the Screening Visit.
• Receipt of any investigational (ie, unapproved) medication within 30 days prior to the Screening Visit.
• 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.
• Drug or alcohol dependency in the past 12 months.
• History of malignant melanoma.
• Clinically significant medical, surgical, or laboratory abnormality in the opinion of the Investigator.
• 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.
• History of clinically significant hallucinations during the past 6 months.
• History of clinically significant impulse control disorder(s).
• Dementia that precludes providing informed consent or would interfere with participation in the study.
• 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.

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (3)

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

Parkinson's Disese Treatment Center of SW Florida

Port Charlotte, Florida, 33980, United States

Location

QUEST Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Related Publications (1)

• 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.

  PMID: 33991326 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

Apomorphine

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

Results Point of Contact

• Title: CNS Medical Director
• Organization: Sunovion Pharmaceuticals Inc.

clinicaltrialsdisclosure@sunovion.com

1-866-503-6351

Study Officials

• CNS Mecdical Director

  Sunovion Pharmacetuicals Inc.

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: September 25, 2017
• Study Start: August 22, 2017
• Primary Completion: March 5, 2019
• Study Completion: March 5, 2019
• Last Updated: August 13, 2020
• Results First Posted: August 13, 2020

Record last verified: 2020-08

Locations

US (3)