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

Primary Purpose

Healthy Participants, Narcolepsy

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

TAK-925

Placebo

About this trial

This is an interventional treatment trial for Healthy Participants

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Sumida Hospital
Hakata Clinic
PS Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

Cohort A1; TAK-925 (Dose Level A1)

Cohort A2; TAK-925 (Dose Level A2)

Cohort A3; TAK-925 (Dose Level A3)

Cohort A4; TAK-925 (Dose Level A4)

Cohort A5; TAK-925 (Dose Level A5)

Cohort A6; TAK-925 (Dose Level A6)

Part A (Cohorts A1-A6); TAK-925 Placebo

Cohort B1; TAK-925 (Dose Level B1)

Cohort B2; TAK-925 (Dose Level B2)

Cohort B3; TAK-925 (Dose Level B3)

Cohort B4; TAK-925 (Dose Level B4)

Part B (Cohorts B1-B4); TAK-925 Placebo

Cohort C1; TAK-925 (Dose Level C1)

Cohort C2; TAK-925 (Dose Level C2)

Part C (Cohorts C1-C2); TAK-925 Placebo

Cohort A'1; TAK-925 (Dose Level A'1)

Cohort A'2; TAK-925 (Dose Level A'2)

Arm Description

TAK-925, Dose Level A, once daily for up to 7 days in healthy participants.

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.

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.

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.

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.

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.

TAK-925 Placebo, once daily for up to 7 days in healthy participants.

TAK-925, Dose Level B1, once daily for up to 7 days in participants with narcolepsy.

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.

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.

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.

TAK-925 Placebo, once daily for up to 7 days in participants with narcolepsy.

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.

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.

TAK-925 Placebo, once daily for up to 7 days in participants with narcolepsy.

TAK-925, Dose Level A'1, single dose in healthy participants.

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.

Outcomes

Primary Outcome Measures

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

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

Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925

This assessment was pre-specified to be conducted for participants in "Part A', Cohort A'1: TAK-925 112 mg" as exploratory measures.

Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925

This assessment was pre-specified to be conducted for participants in "Part A', Cohort A'1: TAK-925 112 mg" as exploratory measures.

Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925

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.

Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 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.

Full Information

NCT ID

NCT03748979

First Posted

November 15, 2018

Last Updated

December 3, 2020

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT03748979

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

November 21, 2018 (Actual)

Primary Completion Date

October 24, 2019 (Actual)

Study Completion Date

October 24, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Healthy Participants, Narcolepsy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

57 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort A1; TAK-925 (Dose Level A1)

Arm Type

Experimental

Arm Description

TAK-925, Dose Level A, once daily for up to 7 days in healthy participants.

Arm Title

Cohort A2; TAK-925 (Dose Level A2)

Arm Type

Experimental

Arm Description

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.

Arm Title

Cohort A3; TAK-925 (Dose Level A3)

Arm Type

Experimental

Arm Description

Arm Title

Cohort A4; TAK-925 (Dose Level A4)

Arm Type

Experimental

Arm Description

Arm Title

Cohort A5; TAK-925 (Dose Level A5)

Arm Type

Experimental

Arm Description

Arm Title

Cohort A6; TAK-925 (Dose Level A6)

Arm Type

Experimental

Arm Description

Arm Title

Part A (Cohorts A1-A6); TAK-925 Placebo

Arm Type

Placebo Comparator

Arm Description

TAK-925 Placebo, once daily for up to 7 days in healthy participants.

Arm Title

Cohort B1; TAK-925 (Dose Level B1)

Arm Type

Experimental

Arm Description

TAK-925, Dose Level B1, once daily for up to 7 days in participants with narcolepsy.

Arm Title

Cohort B2; TAK-925 (Dose Level B2)

Arm Type

Experimental

Arm Description

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.

Arm Title

Cohort B3; TAK-925 (Dose Level B3)

Arm Type

Experimental

Arm Description

Arm Title

Cohort B4; TAK-925 (Dose Level B4)

Arm Type

Experimental

Arm Description

Arm Title

Part B (Cohorts B1-B4); TAK-925 Placebo

Arm Type

Placebo Comparator

Arm Description

TAK-925 Placebo, once daily for up to 7 days in participants with narcolepsy.

Arm Title

Cohort C1; TAK-925 (Dose Level C1)

Arm Type

Experimental

Arm Description

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.

Arm Title

Cohort C2; TAK-925 (Dose Level C2)

Arm Type

Experimental

Arm Description

Arm Title

Part C (Cohorts C1-C2); TAK-925 Placebo

Arm Type

Placebo Comparator

Arm Description

TAK-925 Placebo, once daily for up to 7 days in participants with narcolepsy.

Arm Title

Cohort A'1; TAK-925 (Dose Level A'1)

Arm Type

Experimental

Arm Description

TAK-925, Dose Level A'1, single dose in healthy participants.

Arm Title

Cohort A'2; TAK-925 (Dose Level A'2)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

TAK-925

Intervention Description

TAK-925

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

TAK-925 Placebo

Primary Outcome Measure Information:

Title

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

Description

Time Frame

From the first dose of study drug up to 7 days after the last dose of study drug (up to Day 15)

Secondary Outcome Measure Information:

Title

Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925

Description

This assessment was pre-specified to be conducted for participants in "Part A', Cohort A'1: TAK-925 112 mg" as exploratory measures.

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

Title

Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925

Description

This assessment was pre-specified to be conducted for participants in "Part A', Cohort A'1: TAK-925 112 mg" as exploratory measures.

Time Frame

Title

Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925

Description

Time Frame

Title

Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7

Description

Time Frame

Baseline, Day 1 and Day 7

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

Facility Name

Sumida Hospital

City

Sumida-ku

State/Province

Tokyo

Country

Japan

Facility Name

Hakata Clinic

City

Fukuoka

Country

Japan

Facility Name

PS Clinic

City

Fukuoka

Country

Japan

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing URL

https://vivli.org/ourmember/takeda/

Learn more about this trial

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

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