A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TAK-925 in Healthy Volunteers and Participants With Narcolepsy

• ClinicalTrials.gov Identifier: NCT03748979
• Recruitment Status: Completed
• First Posted: November 21, 2018
• Results First Posted: December 8, 2020
• Last Update Posted: December 8, 2020
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Study Description

Brief Summary:

The purpose of this study is to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-925 when administered to healthy participants and narcolepsy participants.

Condition or disease	Intervention/treatment	Phase
Healthy Participants; Narcolepsy	Drug: TAK-925; Drug: Placebo	Phase 1

Detailed Description:

The drug being tested in this study is called TAK-925. TAK-925 is being tested in healthy participants and participants with narcolepsy. This study will look at the safety, tolerability, pharmacokinetics, and efficacy of TAK-925.

This study will consist of three parts. Part A will be a randomized, double-blind, placebo-controlled, multiple rising dose (MRD) study in healthy participants. Part B is a randomized, double-blind, placebo-controlled MRD study in participants with narcolepsy. Part C is a randomized, double-blind, placebo-controlled, parallel group, multiple repeat dose study in participants with narcolepsy. Part A' is a single dose study in healthy participants.

The study will enroll approximately 96 participants planned as total. All participants except Part A' will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participants and study doctor during the study (unless there is an urgent medical need):

Part A:

• TAK-925 (Dose Levels A1-A6)
• Placebo

Part B:

• TAK-925 (Dose Levels B1-B4)
• Placebo

Part C:

• TAK-925 (Dose Levels C1-C2)
• Placebo

Part A':

• TAK-925 (Dose Levels A'1-A'2)

All participants will be asked to take TAK-925 or Placebo at the same time each day from Day 1 to Day 7 in Parts A, B and C, and take TAK-925 on Day 1 in Part A'.

This multi-center trial will be conducted in Japan. The overall study period is approximately 15 days in Parts A, B and C, and approximately 7 days for Part A'. Participants will be partly admitted to a hospital during the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 3-Part, Randomized, Double-Blind, Placebo-Controlled, Multiple Rising Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TAK-925 in Healthy Volunteers and Patients With Narcolepsy
• Actual Study Start Date: November 21, 2018
• Actual Primary Completion Date: October 24, 2019
• Actual Study Completion Date: October 24, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort A1; TAK-925 (Dose Level A1); TAK-925, Dose Level A, once daily for up to 7 days in healthy participants.	Drug: TAK-925; TAK-925
Experimental: Cohort A2; TAK-925 (Dose Level A2); TAK-925, Dose Level A2, once daily for up to 7 days in healthy participants. Dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort A3; TAK-925 (Dose Level A3); TAK-925, Dose Level A3, once daily for up to 7 days in healthy participants. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort A4; TAK-925 (Dose Level A4); TAK-925, Dose Level A4, once daily for up to 7 days in healthy participants. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort A5; TAK-925 (Dose Level A5); TAK-925, Dose Level A5, once daily for up to 7 days in healthy participants. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort A6; TAK-925 (Dose Level A6); TAK-925, Dose Level A6, once daily for up to 7 days in healthy elderly participants. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Placebo Comparator: Part A (Cohorts A1-A6); TAK-925 Placebo; TAK-925 Placebo, once daily for up to 7 days in healthy participants.	Drug: Placebo; TAK-925 Placebo
Experimental: Cohort B1; TAK-925 (Dose Level B1); TAK-925, Dose Level B1, once daily for up to 7 days in participants with narcolepsy.	Drug: TAK-925; TAK-925
Experimental: Cohort B2; TAK-925 (Dose Level B2); TAK-925, Dose Level B2, once daily for up to 7 days in participants with narcolepsy. Dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort B3; TAK-925 (Dose Level B3); TAK-925, Dose Level B3, once daily for up to 7 days in participants with narcolepsy. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort B4; TAK-925 (Dose Level B4); TAK-925, Dose Level B4, once daily for up to 7 days in participants with narcolepsy. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Placebo Comparator: Part B (Cohorts B1-B4); TAK-925 Placebo; TAK-925 Placebo, once daily for up to 7 days in participants with narcolepsy.	Drug: Placebo; TAK-925 Placebo
Experimental: Cohort C1; TAK-925 (Dose Level C1); TAK-925, Dose Level C1, once daily for up to 7 days in participants with narcolepsy. Dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort C2; TAK-925 (Dose Level C2); TAK-925, Dose Level C2, once daily for up to 7 days in participants with narcolepsy. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Placebo Comparator: Part C (Cohorts C1-C2); TAK-925 Placebo; TAK-925 Placebo, once daily for up to 7 days in participants with narcolepsy.	Drug: Placebo; TAK-925 Placebo
Experimental: Cohort A'1; TAK-925 (Dose Level A'1); TAK-925, Dose Level A'1, single dose in healthy participants.	Drug: TAK-925; TAK-925
Experimental: Cohort A'2; TAK-925 (Dose Level A'2); TAK-925, Dose Level A'2, single dose in healthy participants. Dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) [ Time Frame: From the first dose of study drug up to 7 days after the last dose of study drug (up to Day 15) ]
   An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE with an onset that occurs after receiving study drug.

Secondary Outcome Measures :

1. Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 [ Time Frame: Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf ]
   This assessment was pre-specified to be conducted for participants in "Part A', Cohort A'1: TAK-925 112 mg" as exploratory measures.
2. Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 [ Time Frame: Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf ]
   This assessment was pre-specified to be conducted for participants in "Part A', Cohort A'1: TAK-925 112 mg" as exploratory measures.
3. Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925 [ Time Frame: Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf ]
   Accumulation Ratio of AUC was calculated as AUCtau on Day 7 divided by AUCtau on Day 1. This assessment was pre-specified to be conducted for participants in "Part A', Cohort A'1: TAK-925 112 mg" as exploratory measures.
4. Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 [ Time Frame: Baseline, Day 1 and Day 7 ]
   The MWT is a validated objective measure that is used to measure excessive daytime sleepiness in clinical studies. It has been used as a secondary outcome measure for excessive daytime sleepiness. The MWT evaluates a person's ability to remain awake under soporific conditions for a defined period of time. Wakefulness in this study was measured indirectly by time to fall asleep using MWT. In this study, four 40-minute (1 session) MWT assessments per day was administered on Baseline, Day 1 and Day 7. MWT sleep latency ranges from 0 to 40 minutes, with longer sleep latency indicating greater ability to stay awake.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

Healthy adult participants and Healthy elderly participants:

• Participant weighs at least 50 kg (Healthy adults participants) / 40 kilogram (kg) (Healthy elderly participants) and has a body mass index (BMI) from 18.5 to 30 kilogram per square meter (kg/m^2), inclusive at Screening.

Narcolepsy participants:

• Participants weighs at least 40 kg inclusive at Screening (>=50 kg is required for Cohort B4).
• A diagnosis of narcolepsy, as defined by the International Classification of Sleep Disorders, Third Edition (ICSD-3).
• At Day -1, Epworth sleepiness scale (ESS) score >=10

Exclusion Criteria:

All Participants:

• Participants consume excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.
• Participants have a moderate to severe substance use disorder.
• Participants have a risk of suicide according to endorsement of item 4 or 5 with Screening/Baseline visit C-SSRS (Columbia Suicide Severity Rating Scale) or has made a suicide attempt in the previous 6 months.
• Participants have a lifetime history of major psychiatric disorder, such as bipolar disorder or schizophrenia.
• Participants experienced sleep wake cycle disturbance with external factors such as irregular work hours.

Contacts and Locations

Locations

Japan

Sumida Hospital

Sumida-ku, Tokyo, Japan

Hakata Clinic

Fukuoka, Japan

PS Clinic

Fukuoka, Japan

Sponsors and Collaborators

Takeda

Investigators

• Study Director: Medical Director; Takeda

  Study Documents (Full-Text)

Documents provided by Takeda:

Statistical Analysis Plan  [PDF] October 28, 2019

Study Protocol  [PDF] June 12, 2019

More Information

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03748979
• Other Study ID Numbers: TAK-925-1003; U1111-1221-3144 ( Other Identifier: WHO ); JapicCTI-184207 ( Registry Identifier: JapicCTI )
• First Posted: November 21, 2018
• Results First Posted: December 8, 2020
• Last Update Posted: December 8, 2020
• Last Verified: December 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: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Narcolepsy; Disorders of Excessive Somnolence; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders