A Study of TAK-071 in People With Parkinson Disease

NCT04334317 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: TAK-071-2002U1111-1247-0357
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 21

Brief 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.

Conditions

Parkinson Disease; Healthy Participants

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (6)

• 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, 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, 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

• 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)

Secondary Outcomes (8)

• Main Cohort: Change From Baseline in Global Cognition Z-score

  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

Study Arms (4)

Placebo + TAK-071 (PD Participants)

EXPERIMENTAL

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; Drug: Placebo

TAK-071 + Placebo (PD Participants)

EXPERIMENTAL

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; Drug: Placebo

Sentinel Cohort: Placebo (Healthy Participants)

EXPERIMENTAL

A single dose of TAK-071 placebo-matching mg, tablet, orally, on Day 1.

Drug: Placebo

Sentinel Cohort: TAK-071 7.5 mg (Healthy Participants)

EXPERIMENTAL

A single dose of TAK-071 ≤ 7.5 milligrams (mg), tablet, orally, on Day 1.

Drug: TAK-071

Interventions

TAK-071 DRUG

TAK-071 tablet.

Placebo + TAK-071 (PD Participants); Sentinel Cohort: TAK-071 7.5 mg (Healthy Participants); TAK-071 + Placebo (PD Participants)

Placebo DRUG

TAK-071 placebo-matching tablet.

Placebo + TAK-071 (PD Participants); Sentinel Cohort: Placebo (Healthy Participants); TAK-071 + Placebo (PD Participants)

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is an outpatient of any sex aged between 40 and ≤ 85 years, inclusive, at the time of consent.
• 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.
• Has Hoehn and Yahr stage ≥2 and \<4 at the screening visit.
• 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.
• 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).
• 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.
• \. 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.

You may not qualify if:

• 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.
• 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.
• 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).
• 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.
• 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.
• Participants has body mass index (BMI) less than 18 or greater than 40.
• 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).
• 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.
• The participant is taking warfarin.

Sponsors & Collaborators

• Takeda: lead
• Michael J. Fox Foundation for Parkinson's Research: collaborator

Study Sites (21)

Collaborative Neuroscience Network, LLC

Garden Grove, California, 92845, United States

Location

University of California Irvine Medical Center

Irvine, California, 92697, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Rocky Mountain Movement Disorders Center

Englewood, Colorado, 80113, United States

Location

PPD Phase 1 Clinic

Orlando, Florida, 32806, United States

Location

Infinity Clinical Research, LLC

Sunrise, Florida, 33351, United States

Location

USF Medical Clinic

Tampa, Florida, 33612, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Feinberg School of Medicine Northwestern University

Chicago, Illinois, 60611, United States

Location

Indiana University Health Neuroscience Center

Indianapolis, Indiana, 46202, United States

Location

Quest Research Institute - Hunt - PPDS

Farmington Hills, Michigan, 48334, United States

Location

Park Nicollet Health Services

Golden Valley, Minnesota, 55427, United States

Location

University of Rochester Medicine - Movement Disorders Unit

Rochester, New York, 14618, United States

Location

Neurology Diagnostics, Inc. - ERG - PPDS

Dayton, Ohio, 45459, United States

Location

University of Philadelphia

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina - PPDS

Charleston, South Carolina, 29425, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Central Texas Neurology

Round Rock, Texas, 78681, United States

Location

Meridian Clinical Research

Norfolk, Virginia, 23502, United States

Location

Evergreen Hospital Medical Center

Kirkland, Washington, 98034, United States

Location

Inland Northwest Research

Spokane, Washington, 99202-6290, United States

Location

Related Publications (1)

• Shanbhag NM, Padmanabhan JL, Zhang Z, Harel BT, Jia H, Kangarloo T, Yin W, Dowling AV, Laurenza A, Khudyakov P, Galinsky K, Latzman RD, Simuni T, Weintraub D, Horak FB, Lustig C, Maruff P, Simen AA. An Acetylcholine M1 Receptor-Positive Allosteric Modulator (TAK-071) in Parkinson Disease With Cognitive Impairment: A Phase 2 Randomized Clinical Trial. JAMA Neurol. 2025 Feb 1;82(2):152-159. doi: 10.1001/jamaneurol.2024.4519.

  PMID: 39761063 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Parkinson Disease

Interventions

TAK-071

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: April 6, 2020
• Study Start: October 21, 2020
• Primary Completion: February 27, 2023
• Study Completion: February 27, 2023
• Last Updated: May 14, 2024
• Results First Posted: May 14, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (21)