A Study of TAK-071 in People With Parkinson Disease

A Randomized, Double-blind, Placebo-Controlled, 2-Period Crossover, Phase 2 Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral TAK-071 in Parkinson Disease Patients With Cognitive Impairment and an Elevated Risk of Falls

It is hoped that TAK-071 will help people with Parkinson's disease to walk with better balance. The main aim of the study is to check if there is a difference in how participants walk after treatment with TAK-071. Another aim is to see if it improves how participants think and remember.

At the first visit, the study doctor will check who can take part. Participants who can take part will be picked for 1 of 2 groups by chance.

Both groups will have 2 treatments but in a different order. The treatments are TAK-071 tablets or placebo. In this study, a placebo will look like the TAK-071 but will not have any medicine in it.

One group will take TAK-071 for 6 weeks, have at least a 3-week break, then take a placebo for 6 weeks. The other group will take a placebo for 6 weeks, have at least a 3-week break, then take TAK-071 for 6 weeks. The participants will not know the order of their 2 treatments, nor will their study doctors. This is to help make sure the results are more reliable.

The participants will visit the clinic at the beginning and end of each treatment for a check-up. 14 days after the 2nd treatment, clinic staff will telephone the participants for a final check-up.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease; Healthy Participants
• Intervention / Treatment: Drug: TAK-071; Drug: Placebo

Detailed Description

The drug being tested in this study is TAK-071. TAK-071 is being tested to treat people with PD who have cognitive impairment and are at risk for falls and who are not concurrently taking acetylcholinesterase inhibitors. The study will look at the efficacy and safety of TAK-071 in participants with PD who take TAK-071 versus placebo.

The study will also evaluate the PK of TAK-071 in healthy participants (sentinel cohort) older than 55 years.

The study will enroll approximately 74 participants. An initial sentinel cohort of 10 healthy participants will be included to estimate age effects. Participants aged 56 to 75 years will be randomly assigned in 3:1 ratio to one of the two treatments:

• Sentinel Cohort: TAK-071 7.5 mg
• Sentinel Cohort: Placebo

Enrolment for participants aged 40 to ≤ 85 years in the main study will start simultaneously with sentinel cohort. Based on PK, safety, and physiologically based PK modelling data from sentinel cohort, dosing will be decided for the remaining participants. Participants with maximum age of 66 to 85 years, inclusive, will be enrolled at a dose of 5 mg, and the dose for subjects aged 40 to 65 years, inclusive, will be 7.5 mg. All participants will be asked to take one tablet at the same time each day throughout the study.

The remaining participants aged 40 years to <=85 years will be randomly assigned in 1:1 ratio to one of two treatment sequences in crossover design:

• TAK-071 + Placebo
• Placebo + TAK-071

The study will be conducted in the United States. The minimum time to participate in this study is approximately 15 weeks. Participants will make multiple visits to the clinic and will have home assessments during the third Week of each 6-week treatment period, and will be contacted by telephone at 14 days after completion of the last period for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, LLC
    • Irvine, California, United States, 92697
      • University of California Irvine Medical Center
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Movement Disorders Center
  • Florida
    • Orlando, Florida, United States, 32806
      • PPD Phase 1 Clinic
    • Sunrise, Florida, United States, 33351
      • Infinity Clinical Research, LLC
    • Tampa, Florida, United States, 33612
      • USF Medical Clinic
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Feinberg School of Medicine Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Neuroscience Center
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute - Hunt - PPDS
  • Minnesota
    • Golden Valley, Minnesota, United States, 55427
      • Park Nicollet Health Services
  • New York
    • Rochester, New York, United States, 14618
      • University of Rochester Medicine - Movement Disorders Unit
  • Ohio
    • Dayton, Ohio, United States, 45459
      • Neurology Diagnostics, Inc. - ERG - PPDS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • University of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina - PPDS
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Round Rock, Texas, United States, 78681
      • Central Texas Neurology
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Meridian Clinical Research
  • Washington
    • Kirkland, Washington, United States, 98034
      • Evergreen Hospital Medical Center
    • Spokane, Washington, United States, 99202-6290
      • Inland Northwest Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Is an outpatient of any sex aged between 40 and ≤ 85 years, inclusive, at the time of consent.
2. Has a diagnosis of PD according to Movement Disorders Society (MDS) clinical diagnostic criteria for PD. Participants with DLB (i.e., dementia diagnosed before onset of motor symptoms or up to 1 year after onset of motor symptoms) are also eligible, consistent with MDS clinical diagnostic criteria for PD.
3. Has Hoehn and Yahr stage ≥2 and <4 at the screening visit.
4. Has elevated risk for falls as indicated by at least 1 fall in the last 12 months before the screening visit based on the Fall History Assessment where in the opinion of the investigator the falls were a consequence of PD and are at continued elevated risk of falls per investigator judgment. Investigator judgment on fall risk may be informed by information such as, but not limited to, history, physical examination and/or a score ≥2 on item 3.10 on Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III.
5. Has evidence of cognitive impairment as indicated by a Montreal Cognitive Assessment (MoCA) score between 11 and 26, inclusive and additionally can complete the cognitive assessments at screening (as specified in the study manual).
6. Can walk without aid for 2 minutes while doing serial 3 subtraction (with site staff ensuring participant safety in case of falls). Participants who require aids for walking can be included as long as they can complete the walk test without aid.

Inclusion For Healthy Participants:

1. The participant is a healthy individual of either sex aged between 56 and 75 years, inclusive (for initial set of participant in the sentinel cohort) at the time of consent. Older participants may be enrolled after analysis of data from participants aged 56 to 75 years, inclusive.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Key Exclusion Criteria:

1. Has orthostatic hypotension at screening, as defined as a decline in systolic blood pressure greater than 20 mm Hg or a decrease of 10 mm Hg in diastolic blood pressure on standing measured within 1 minute after being supine for at least 5 minutes.
2. Has dyskinesia of sufficient severity to interfere with digital gait assessments during visits (as defined by Movement Disorders Society - Unified Parkinson's Disease Rating Scale [MDS-UPDRS] section 4.1 "Time spent with dyskinesias" and/or section 4.2 "Functional Impact of Dyskinesias" scores greater than [>] 2), or in the opinion of the investigator the participant's dyskinesia is likely to interfere with the digital gait assessments.
3. Has significant risk factors for seizures (a history of seizures as an adult, a history of brain injury, or other risk factors deemed relevant by the investigator).
4. Is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property, or the participant has attempted suicide within the past year before screening. Participants who have positive answers on item number 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) (based on the past year) before randomization are excluded.
5. Is unwilling or unable to discontinue taking cholinesterase inhibitors and/or moderate or strong cytochrome P-450 3A4 inhibitors or inducers at least 30 days before randomization.

Exclusion For Healthy Participants:

1. Participants has body mass index (BMI) less than 18 or greater than 40.
2. Has significant risk factors for seizures (a history of seizures as an adult, a history of brain injury, or other risk factors deemed relevant by the investigator).
3. The participant is unwilling or unable to discontinue taking cholinesterase inhibitors and/or moderate or strong CYP 3A4 inhibitors or inducers at least 30 days before randomization.
4. The participant is taking warfarin.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sentinel Cohort: TAK-071 7.5 mg (Healthy Participants); A single dose of TAK-071 ≤ 7.5 milligrams (mg), tablet, orally, on Day 1.	Drug: TAK-071; TAK-071 tablet.
Experimental: Sentinel Cohort: Placebo (Healthy Participants); A single dose of TAK-071 placebo-matching mg, tablet, orally, on Day 1.	Drug: Placebo; TAK-071 placebo-matching tablet.
Experimental: TAK-071 + Placebo (PD Participants); TAK-071 tablets, orally, once daily for up to first 6 weeks in Period 1, followed by ≥3 weeks washout period, followed by TAK-071 placebo-matching tablets, orally, once daily for up to next 6 weeks in Period 2.	Drug: TAK-071; TAK-071 tablet.; Drug: Placebo; TAK-071 placebo-matching tablet.
Experimental: Placebo + TAK-071 (PD Participants); TAK-071 placebo-matching tablets, orally, once daily for up to first 6 weeks in Period 1, followed by ≥3 weeks washout period, followed by TAK-071 tablets, orally, once daily for up to next 6 weeks in Period 2.	Drug: TAK-071; TAK-071 tablet.; Drug: Placebo; TAK-071 placebo-matching tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sentinel Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-071 in Healthy Participants		Day 1: pre-dose and Day 2 to 8: post-dose and at multiple time-points (up to approximately 168 hours)
Sentinel Cohort, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-071 in Healthy Participants		Day 1: pre-dose and Day 2 to 8: post-dose and at multiple time-points (up to approximately 168 hours)
Sentinel Cohort, AUClast: Area Under The Concentration-Time Curve From Time 0 To The Last Quantifiable Concentration in Healthy Participants		Day 1: pre-dose and Day 2 to 8: post-dose and at multiple time-points (up to approximately 168 hours)
Sentinel Cohort, AUCinf: Area Under The Concentration-Time Curve From Time 0 To Infinity in Healthy Participants		Day 1: pre-dose and Day 2 to 8: post-dose and at multiple time-points (up to approximately 168 hours)
Main Cohort: Change From Baseline in Stride Time (Gait) Variability During a 2-minute Dual-Task Walking Test After 6-week Treatment With TAK-071 Compared With Placebo	Stride time (or gait) is defined as the time elapsed between the first contact of two consecutive footsteps of the same foot and is expressed in seconds. The standard deviation (SD) of the stride time, recorded for each foot during the 2-minutes, is averaged to obtain stride time (gait) variability. The 2-minute walk was performed with and without simultaneous performance of serial 3 subtraction, which adds a cognitive load to the task. Data are reported with and without cognitive load.	Baseline and Week 6 (for each study period)
Sentinel Cohort, AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours for TAK-071 in Healthy Participants		Day 1: Predose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Main Cohort: Change From Baseline in Global Cognition Z-score	The global cognition score was calculated as the average of the available z-scores derived from the following individual cognitive tests administered in the cognitive test battery: 'Executive Function' assessed by One Back Test, Modified Groton Maze Learning Test, 'Memory' assessed by One Card Learning Test, International Shopping List Test - Immediate and Delayed Recall Tests, and 'Attention' assessed by Sustained Attention Test and Symbol Digit Modalities Test. Each raw score on the individual tests was converted to a z-score. A global z-score was calculated as an average of the individual z-scores. As the analysis is based on z-scores, there is no minimum or maximum value. An individual z-score of 0 means the observed score is the same as the group mean score at baseline. A positive z-score means the observed score is better (improvement in cognition) than the group mean score at baseline.	Baseline and Week 6 (for each study period)
Main Cohort: Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-071 in Parkinson Disease (PD) Participants		Day 42 of Period 1 and Period 2: pre-dose and at multiple time-points post-dose
Main Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-071 in PD Participants		Day 1 of Period 1 and Period 2: pre-dose and at multiple time-points post-dose
Main Cohort: Cmax,ss: Maximum Observed Plasma Concentration at Steady State for TAK-071 in PD Participants		Day 42 of Period 1 and Period 2: pre-dose and at multiple time-points post-dose
Main Cohort: AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours for TAK-071 in PD Participants		Day 1 of Period 1 and Period 2: pre-dose and at multiple time-points post-dose
Main Cohort, AUCtau: Area Under the Plasma Concentration-time Curve During a Dosing Interval for TAK-071 in PD Participants		Day 42 of Period 1 and Period 2: pre-dose and at multiple time-points post-dose
Main Cohort, Tmax,ss: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State for TAK-071 in PD Participants		Day 1 of Period 1 and Period 2: pre-dose and at multiple time-points post-dose
Main Cohort: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-071 in PD Participants		Day 42 of Period 1 and Period 2: pre-dose and at multiple time-points post-dose

Collaborators and Investigators

• Sponsor: Takeda
• Collaborators: Michael J. Fox Foundation for Parkinson's Research
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2020
• Primary Completion (Actual): February 27, 2023
• Study Completion (Actual): February 27, 2023

Study Registration Dates

• First Submitted: March 30, 2020
• First Submitted That Met QC Criteria: April 2, 2020
• First Posted (Actual): April 6, 2020

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Drug Therapy
• 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
• Other Study ID Numbers: TAK-071-2002; U1111-1247-0357 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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