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

Tracking Information

• First Submitted Date: March 30, 2020
• First Posted Date: April 6, 2020
• Last Update Posted Date: November 20, 2020
• Actual Study Start Date: October 21, 2020
• Estimated Primary Completion Date: March 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 13, 2020)

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.

Original Primary Outcome Measures (submitted: April 2, 2020)

• 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.
• Number of Participants with At least one Adverse Event (AE) [ Time Frame: Up to Week 6 (for each study period) ]
  An AE is defined as any untoward medical occurrence in a clinical investigation where a participant is administered a drug; it does not necessarily have to have a causal relationship with this treatment.
• Number of Participants with Clinically Significant Laboratory Values Reported as an Adverse Event [ Time Frame: Up to Week 6 (for each study period) ]
  Clinical laboratory parameters including tests for serum chemistry, hematology and urinalysis.
• Number of Participants with Clinically Significant Electrocardiogram (ECG) Findings Reported as an Adverse Event [ Time Frame: Up to Week 6 (for each study period) ]
  A standard 12-lead ECG will be recorded.
• Number of Participants with Clinically Significant Physical Examination Findings Reported as an Adverse Event [ Time Frame: Up to Week 6 (for each study period) ]
  Summary by system organ class and preferred terms of AEs.
• Number of Participants with Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using the Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Up to Week 6 (for each study period) ]
  The Columbia-Suicide Severity Rating Scale (C-SSRS) will be administered to asses Suicidal Ideation and Suicidal Behavior.
• Change from Baseline in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) for Worsening of Motor or Nonmotor Symptoms [ Time Frame: Baseline and Week 6 (for each study period) ]
  The MDS-UPDRS has four parts: Part 1 (non-motor experiences of daily living), Part 2 (motor experiences of daily living), Part 3 (motor examination) and Part 4 (motor complications). The MDS-UPDRS includes five possible severity ratings for each item in each part, ranging from 0(normal) to 4(severe). Total scores from each part will be analysed separately.

Current Secondary Outcome Measures (submitted: August 13, 2020)

• 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.
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]

Original Secondary Outcome Measures (submitted: April 2, 2020)

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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of TAK-071 on Falls in Participants With Parkinson Disease (PD)
• 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
• 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.

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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Parkinson's Disease

Intervention

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

Study Arms

• 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.
  Interventions:

  • Drug: TAK-071
  • Drug: Placebo
• 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.
  Interventions:

  • Drug: TAK-071
  • Drug: Placebo
• 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.
  Interventions:

  • Drug: TAK-071
  • Drug: Placebo
• 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.
  Interventions:

  • Drug: TAK-071
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 2, 2020): 64
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2022
• Estimated Primary Completion Date: March 31, 2022 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04334317
• Other Study ID Numbers: TAK-071-2002; U1111-1247-0357 ( Other Identifier: WHO )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: 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/

• Responsible Party: Takeda
• Study Sponsor: Takeda
• Collaborators: Michael J. Fox Foundation for Parkinson's Research

Investigators

• Study Director: Medical Director Clinical Science; Takeda

• PRS Account: Takeda
• Verification Date: November 2020