Parkinson's Disease With Mild Cognitive Impairment Treated With Nicotinic Agonist Drug

NCT04810104 | Withdrawn Phase 2 DMC

• 2 other identifiers: PD-MIND2019-002423-15
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To test for the first time the potential of a nicotinic agonist on cognitive symptoms in people with mild cognitive impairment (MCI) in Parkinson's disease (PD), referred to as PD-MCI.

Conditions

Parkinson Disease; Mild Cognitive Impairment

Keywords

Parkinson's Disease; Mild Cognitive Impairment; Cognition

Outcome Measures

Primary Outcomes (1)

• Change in Attentional Intensity Index composite factor score from baseline to week 12

  The Attentional Intensity Index composite factor score combines the speed scores from the three attention tasks (simple reaction time, choice reaction time and digit vigilance), and has been validated using factor analysis. The measure reflects the ability to focus attention and process information.

  From baseline to week 12 (end of treatment period).

Secondary Outcomes (21)

• Change in Attentional Intensity Index composite factor score from baseline to week 6

  From baseline to week 6 (mid-point of treatment period)

• Change in Sustained Attention Index composite factor score from baseline to week 6 and week 12

  From baseline to week 6 (mid-point of treatment period) and week 12 (end of treatment period)

• Change in Working Memory Index composite factor score from baseline to week 6 and week 12

  From baseline to week 6 (mid-point of treatment period) and week 12 (end of treatment period)

• Change in Episodic Memory Index composite factor score from baseline to week 6 and week 12

  From baseline to week 6 (mid-point of treatment period) and week 12 (end of treatment period)

• Change in Memory Speed Retrieval Index composite factor score from baseline to week 6 and week 12

  Fom baseline to week 6 (mid-point of treatment period) and week 12 (end of treatment period)

Other Outcomes (5)

• Screening/Baseline whole-brain and regionally specific brain volumes as predictors of treatment response

  At screening/baseline (pre-medication dosing)

• Screening/Baseline whole-brain perfusion as well as perfusion in ROIs as predictors of treatment response

  At screening/baseline (pre-medication dosing)

• Screening/Baseline functional resting-state connectivity of the large-scale cognitive brain networks as predictors of treatment response

  At screening/baseline (pre-medication dosing)

Study Arms (2)

Active drug: AZD0328

EXPERIMENTAL

Participants will receive AZD0328 capsules for oral administration.AZD0328 is a selective α7 nicotinic receptor agonist, The total daily dosage of AZD0328 is 1mg per day; administered as 0.5mg twice daily / BID. The study treatment period is 12-weeks.

Drug: AZD0328

Placebo

PLACEBO COMPARATOR

Participants will receive identical-appearing placebo capsules for oral administration.Participants will be instructed to take 2 capsules in the morning and 2 capsules in the evening for a 12-week period.

Drug: Placebo

Interventions

AZD0328 DRUG

Active study drug

Active drug: AZD0328

Placebo DRUG

Non-active study drug

Placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 50 to 80 years (inclusive) at time of consent
• Duration of motor symptoms of at least 1 year
• Hoehn and Yahr stage between 1 and 3 (inclusive) in ON state
• Diagnosis of PD according to United Kingdom (UK) Brain Bank criteria
• Score on Clinical Dementia Rating (CDR) scale = 0.5
• Diagnosis of PD-MCI according to MDS PD-MCI, Level I criteria
• Duration of cognitive impairment of at least 3 months (to distinguish from mild delirium)

You may not qualify if:

• Insufficient fluency in English or local language to complete assessments
• Severe visual or auditory impairment that may interfere with participant's ability to complete assessments
• Unable to provide informed consent at screening visit
• Participation in a clinical study involving an investigational drug within 4 months prior to screening
• Smoking (cigarettes, pipes, cigars, e-cigarettes etc.) or use of smokeless tobacco products (chewing / dipping tobacco, snuff etc.) or anti-smoking nicotine containing products (patches/gum/sprays etc.), within the last 12 weeks
• HADS depression subscale score ≥ 11
• History of deep brain stimulation or other neurosurgical procedure
• Diagnosis of dementia, including Parkinson's disease dementia (PDD) or Dementia with Lewy Bodies (DLB).
• Diagnosis of schizophrenia, bipolar disorder or other psychotic disorder
• Malignant neoplasms within 3 years of screening (except for basal or squamous cell carcinoma of the skin); or had curative surgery/treatment and has been free of malignancy for at least 12 months)
• Any medical condition that in the opinion of the investigator may be contributing to cognitive impairment, above and beyond that caused by the participant's PD,
• Current evidence of any other medical condition not stably or adequately controlled, and which in the opinion of the investigator may affect participant safety or study participation
• Using any prohibited medications or permitted medications that do not meet stable dosing regimen requirements, as specified in section 5.7
• Clinically significant vital sign or ECG measure at screening or baseline visit, that in the opinion of the investigator would prevent participant from safely participating in this study
• Clinically significant clinical laboratory result from screening visit, that in the opinion of the investigator would prevent participant from safely participating in this study

Sponsors & Collaborators

• King's College London: lead
• Helse Stavanger HF: collaborator
• Michael J. Fox Foundation for Parkinson's Research: collaborator
• Parkinson's UK: collaborator
• AstraZeneca: collaborator
• Masaryk University: collaborator
• Norges Parkinsonforbund, Norway: collaborator
• University of Exeter: collaborator
• Stichting Lygature: collaborator
• Innovative Medicines Initiative: collaborator

MeSH Terms

Conditions

Parkinson Disease; Cognitive Dysfunction

Interventions

spiro(1-azabicyclo(2.2.2)octane-3,2'(3H)-furo(2,3-b)pyridine)

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Dag Aarsland, PhD

  King's College London; Stavager Univeristy Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomised, double-blind, placebo-controlled, parallel-group, phase 2a study of AZD0328, a selective α7 nicotinic receptor agonist, in PD-MCI.

Study Record Dates

• First Submitted: March 15, 2021
• First Posted: March 22, 2021
• Study Start: October 1, 2022
• Primary Completion: January 1, 2024
• Study Completion: April 1, 2024
• Last Updated: October 14, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share