A Study of TAK-071 in People With Parkinson Disease

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04334317
• Other study ID #: TAK-071-2002
• Secondary ID: U1111-1247-0357
• Status: Completed
• Phase: Phase 2
• Start date: October 21, 2020
• Est. completion date: February 27, 2023

Study information

• Verified date: April 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: February 27, 2023
• Est. primary completion date: February 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Participants
• Parkinson Disease

Intervention

Drug:
• TAK-071
TAK-071 tablet.
• Placebo
TAK-071 placebo-matching tablet.

Locations

Country	Name	City	State
United States	Augusta University	Augusta	Georgia
United States	Medical University of South Carolina - PPDS	Charleston	South Carolina
United States	Feinberg School of Medicine Northwestern University	Chicago	Illinois
United States	Neurology Diagnostics, Inc. - ERG - PPDS	Dayton	Ohio
United States	Rocky Mountain Movement Disorders Center	Englewood	Colorado
United States	Quest Research Institute - Hunt - PPDS	Farmington Hills	Michigan
United States	Collaborative Neuroscience Network, LLC	Garden Grove	California
United States	Park Nicollet Health Services	Golden Valley	Minnesota
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University Health Neuroscience Center	Indianapolis	Indiana
United States	University of California Irvine Medical Center	Irvine	California
United States	Evergreen Hospital Medical Center	Kirkland	Washington
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Meridian Clinical Research	Norfolk	Virginia
United States	PPD Phase 1 Clinic	Orlando	Florida
United States	University of Philadelphia	Philadelphia	Pennsylvania
United States	University of Rochester Medicine - Movement Disorders Unit	Rochester	New York
United States	Central Texas Neurology	Round Rock	Texas
United States	Inland Northwest Research	Spokane	Washington
United States	Infinity Clinical Research, LLC	Sunrise	Florida
United States	USF Medical Clinic	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Takeda	Michael J. Fox Foundation for Parkinson's Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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
Primary	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)
Primary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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