Effect of TAK-071 on Falls in Participants With Parkinson Disease (PD)

• ClinicalTrials.gov Identifier: NCT04334317
• Recruitment Status: Recruiting
• First Posted: April 6, 2020
• Last Update Posted: November 20, 2020
• Sponsor: Takeda
• Collaborator: Michael J. Fox Foundation for Parkinson's Research
• Information provided by (Responsible Party): Takeda

Study Description

Brief Summary:

The purpose of this study is to evaluate the effect of TAK-071 when compared to placebo on gait in participants with PD who also have cognitive impairment. Safety and tolerability of TAK-071 will also be established in participants with PD.

Condition or disease	Intervention/treatment	Phase
Parkinson's Disease	Drug: TAK-071; Drug: Placebo	Phase 2

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.

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 enroll approximately 64 participants. An initial sentinel cohort of 12 participants will be included to estimate age effects. Participants aged 40 to less than or equal to (<=) 65 years will be randomly assigned to one of the two treatment sequences in a crossover design:

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

Enrolment for participants aged 40 to <=65 years in the main study will continue after randomization for the sentinel cohort is completed or nearly completed. Based on PK, safety, and physiologically based PK modeling data from sentinel cohort, dosing will be decided for the remaining participants. If older participants are expected to remain below the exposure caps then participants with maximum age of not more than 85 years may be enrolled and and dose may be modified after analysis of data from the sentinel cohort (7.5 or 5 mg once daily, potentially depending on age). 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 <=65 years will be randomly assigned 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 21, 2020
• Estimated Primary Completion Date: March 31, 2022
• Estimated Study Completion Date: March 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sentinel Cohort: TAK-071 7.5 mg + Placebo; TAK-071 7.5 milligrams (mg), tablets, orally, once daily for up to first 6 weeks in Period 1, followed by greater than or equal to (>=) 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: Sentinel Cohort: Placebo + TAK-071 7.5 mg; 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 7.5 mg 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: TAK-071 + Placebo; 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. Dosage for the remaining participants will be determined depending on pharmacokinetic (PK) results, safety and physiologically based PK modelling data from the sentinel cohort.	Drug: TAK-071; TAK-071 tablet.; Drug: Placebo; TAK-071 placebo-matching tablet.
Experimental: Placebo + TAK-071; 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. Dosage for the remaining participants will be determined depending on PK results, safety and physiologically based PK modelling data from the sentinel cohort.	Drug: TAK-071; TAK-071 tablet.; Drug: Placebo; TAK-071 placebo-matching tablet.

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline in Gait Variability during a 2-minute Dual-Task Walking Test After 6-week Treatment with TAK-071 Compared with Placebo [ Time Frame: Baseline and Week 6 (for each study period) ]
   Variability in gait will be measured at baseline and after 6 weeks of taking TAK-071 or placebo. Participants will be asked to walk back and forth along a 10-meter long hallway for 2 minutes while conducting a serial subtraction test.

Secondary Outcome Measures :

1. Change from Baseline in Global Cognition Profile [ Time Frame: Baseline and Week 6 (for each study period) ]
   Global cognition profile will be assessed using battery of tests to assess attention, executive functioning and memory. All tests would be combined to provide a composite score such that a higher score will indicate better performance.
2. Sentinel Cohort; Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-071 After a Single Dose in Period 1 [ Time Frame: Period 1 Day 1: pre-dose and at multiple time-points (up to approximately 24 hours) post-dose ]
3. Sentinel Cohort; Tmax,ss: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-071 at Steady State in Period 1 [ Time Frame: Period 1 Day 42: pre-dose and at multiple time-points (up to approximately 192 hours) post-dose ]
4. Sentinel Cohort; Cmax: Maximum Observed Plasma Concentration for TAK-071 After a Single Dose in Period 1 [ Time Frame: Period 1 Day 1: pre-dose and at multiple time-points (up to approximately 24 hours) post-dose ]
5. Sentinel Cohort; Cmax,ss: Maximum Observed Plasma Concentration for TAK-071 at Steady State in Period 1 [ Time Frame: Period 1 Day 42: pre-dose and at multiple time-points (up to approximately 192 hours) post-dose ]
6. Sentinel Cohort; AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours for TAK-071 After a Single Dose in Period 1 [ Time Frame: Period 1 Day 1: pre-dose and at multiple time-points (up to approximately 24 hours) post-dose ]
7. Sentinel Cohort; AUC(0-24),ss: Area Under the Plasma Concentration-time Curve from Time 0 to 24 Hours for TAK-071 at Steady State in Period 1 [ Time Frame: Period 1 Day 42: pre-dose and at multiple time-points (up to approximately 24 hours) post-dose ]
8. Sentinel Cohort; Ctrough,ss: Observed Concentration at the End of a Dosing Interval for TAK-071 at Steady State in Period 1 [ Time Frame: Period 1 Day 42: pre-dose and at multiple time-points (up to approximately 192 hours) post-dose ]
9. Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-071 on Day 42 [ Time Frame: Day 42: pre-dose and at multiple time-points (up to approximately 192 hours) post-dose ]
10. Cmax: Maximum Observed Plasma Concentration for TAK-071 [ Time Frame: Days 1 and 64: pre-dose and at multiple time points (up to approximately 2 hours) post-dose; Days 42 and 105: pre-dose and at multiple time-points (up to approximately 3 hours) post-dose ]
11. AUC: Area Under the Plasma Concentration-time Curve for TAK-071 [ Time Frame: Days 1 and 64: pre-dose and at multiple time points (up to approximately 2 hours) post-dose; Days 42 and 105: pre-dose and at multiple time-points (up to approximately 3 hours) post-dose ]
12. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-071 [ Time Frame: Days 1 and 64: pre-dose and at multiple time points (up to approximately 2 hours) post-dose; Days 42 and 105: pre-dose and at multiple time-points (up to approximately 3 hours) post-dose ]

Eligibility Criteria

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

Criteria

Key Inclusion Criteria:

1. Is an outpatient of any sex aged between 40 and <=65 years, inclusive, at the time of consent. At a later date, participants up to age 85 years may be enrolled.
2. Has a diagnosis of PD according to Movement Disorders Society (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 2 falls in the last 6 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.
5. Has evidence of cognitive impairment as indicated by a Montreal Cognitive Assessment (MoCA) score between 18 and 24, inclusive.
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.

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. participant 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations

Contacts

Contact: Takeda Study Registration Call Center; +1-877-825-3327; medinfoUS@takeda.com

Locations

United States, California

Collaborative Neuroscience Network, LLC; Recruiting

Torrance, California, United States, 90502

Cedars Sinai Medical Center; Not yet recruiting

West Hollywood, California, United States, 90048-1804

United States, Colorado

Rocky Mountain Movement Disorders Center; Not yet recruiting

Englewood, Colorado, United States, 80113

United States, Florida

Suncoast Neuroscience Associates Inc; Not yet recruiting

Saint Petersburg, Florida, United States, 33713

Infinity Clinical Research, LLC; Recruiting

Sunrise, Florida, United States, 33351

United States, Georgia

Augusta University; Not yet recruiting

Augusta, Georgia, United States, 30912

United States, Illinois

Feinberg School of Medicine Northwestern University; Not yet recruiting

Chicago, Illinois, United States, 60611

United States, Indiana

Indiana University Health Neuroscience Center; Not yet recruiting

Indianapolis, Indiana, United States, 46202

United States, Michigan

Quest Research institute; Recruiting

Farmington Hills, Michigan, United States, 48334

United States, Pennsylvania

University of Pennsylvania; Not yet recruiting

Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina

Medical University of South Carolina - PPDS; Not yet recruiting

Charleston, South Carolina, United States, 29425

United States, Texas

Baylor College of Medicine; Not yet recruiting

Houston, Texas, United States, 77030-3411

Baylor College of Medicine; Not yet recruiting

Houston, Texas, United States, 77030

United States, Washington

Evergreen Hospital Medical Center; Not yet recruiting

Kirkland, Washington, United States, 98034

Sponsors and Collaborators

Takeda

Michael J. Fox Foundation for Parkinson's Research

Investigators

• Study Director: Medical Director Clinical Science; Takeda

More Information

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT04334317
• Other Study ID Numbers: TAK-071-2002; U1111-1247-0357 ( Other Identifier: WHO )
• First Posted: April 6, 2020
• Last Update Posted: November 20, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• 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.
• URL: https://vivli.org/ourmember/takeda/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda:

Drug Therapy

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases