A Study of the Pharmacokinetics, Pharmacodynamics, and Safety of Opicapone in Subjects With Parkinson's Disease Taking Levodopa.

A Phase 1, Open-Label Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Repeated Doses of Opicapone, and Effect on Levodopa Pharmacokinetics in Subjects With Parkinson's Disease

This is a phase 1, open-label study to assess the pharmacokinetics, pharmacodynamics, safety, and tolerability of opicapone when administered orally once daily for 14 days as adjunctive therapy to carbidopa/levodopa in subjects with Parkinson's disease.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Opicapone; Drug: Carbidopa Levodopa

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Neurocrine Clinical Site
    • Long Beach, California, United States, 90806
      • Neurocrine Clinical Site
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Neurocrine Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Have a clinical diagnosis of idiopathic Parkinson's Disease (PD) for at least 3 years with clear improvement with levodopa treatment
2. Be at a stable dose of maintenance medication(s) for PD, including stable doses of CD/LD
3. Subjects of childbearing potential who do not practice total abstinence must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently during the screening, treatment and follow-up periods of the study
4. Have a body mass index (BMI) of 18 to 40 kg/m2
5. Have a modified Hoehn and Yahr stage of ≤4 in the OFF state
6. Be able to tolerate an overnight period of 12 hours without CD/LD
7. Be in good general health and expected to complete the clinical study as designed

Exclusion Criteria:

1. Are currently pregnant or breastfeeding
2. More than 2 alcoholic beverages daily or more than 14 alcoholic beverages weekly within 7 days of Day -1 or consume any alcohol within 48 hours of Day -1.
3. Have motor fluctuations during the day (ie, effect of levodopa "wearing off" or having unpredictable "off" periods), or severe or intolerable levodopa-induced dyskinesia
4. Have had previous exposure to opicapone, or have an allergy, hypersensitivity, or intolerance to opicapone or other COMT inhibitor.
5. Have a history of a medical condition or surgical procedure that might interfere with absorption or metabolism.
6. Have a known history of neuroleptic malignant syndrome
7. Have an unstable medical condition or chronic disease
8. Have taken certain prohibited medications within 28 days of Day -1.
9. Have a known or suspected diagnosis of AIDS, or have tested seropositive for HIV
10. Have hepatitis A or B
11. Have a significant risk of suicidal or violent behavior

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Opicapone once daily with Carbidopa/Levodopa; Opicapone administered once daily for 14 days; carbidopa/levodopa administered at set frequency on Study Days 1, 2 & 15	Drug: Opicapone; catechol-O-methyltransferase (COMT) inhibitor; Other Names: BIA 9-1067; Drug: Carbidopa Levodopa; Levodopa: dopamine precursor Carbidopa: DOPA decarboxylase inhibitor; Other Names: Sinemet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic evaluation of opicapone and its metabolites: area under the curve (AUC 0-24)	Area under the plasma concentration versus time curve from 0 to 24 hours for analytes with quantifiable concentrations at 24 hours postdose	up to 19 days
Pharmacokinetic evaluation of opicapone and its metabolites: area under the curve (AUC 0-tlast)	Area under the plasma concentration versus time curve from 0 hour to the time of the last measurable concentration for analytes below the limit of quantification at 24 hours postdose	up to 19 days
Pharmacokinetic evaluation of opicapone and its metabolites: Maximum plasma concentration (Cmax)	Maximum plasma concentration	up to 19 days
Pharmacokinetic evaluation of opicapone and its metabolites: Time to maximum plasma concentration (tmax)	Time to maximum plasma concentration	up to 19 days
Pharmacokinetic evaluation of levodopa following administration of opicapone: area under the curve (AUC 0-tlast)	Area under the plasma concentration versus time curve from 0 hours to time before next levodopa dose	up to 15 days
Pharmacokinetic evaluation of levodopa following administration of opicapone: maximum plasma concentration (cmax)	Maximum plasma concentration	up to 15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (safety and tolerability)	Number of participants with reported adverse events after study treatment.	up to 19 days
Pharmacodynamic evaluation of opicapone on S-COMT activity	Maximum inhibition of S-COMT activity.	up to 19 days

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences
• Investigators: Study Director: Chief Medical Officer, Chief Medical Officer

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2018
• Primary Completion (Actual): July 2, 2018
• Study Completion (Actual): July 2, 2018

Study Registration Dates

• First Submitted: March 1, 2018
• First Submitted That Met QC Criteria: April 5, 2018
• First Posted (Actual): April 12, 2018

Study Record Updates

• Last Update Posted (Actual): March 22, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunologic Factors; Dopamine Agonists; Dopamine Agents; Adjuvants, Immunologic; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa; Carbidopa, levodopa drug combination; Opicapone
• Other Study ID Numbers: NBI-OPC-1706

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No