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

Phase 1

Completed

• Conditions: Healthy Participants; Narcolepsy
• Interventions: Drug: TAK-925; Drug: Placebo

• Registration Number: NCT03748979
• Lead Sponsor: Takeda

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.

Study Timeline

• Study First Submitted: 2018-11-15
• Study First Submitted QC: 2018-11-19
• Study Start: 2018-11-21
• Study First Posted: 2018-11-21
• Primary Completion: 2019-10-24
• Study Completion: 2019-10-24
• Results First Submitted: 2020-10-23
• Status Verified: 2020-12
• Results First Submitted QC: 2020-12-03
• Last Update Submitted: 2020-12-03
• Results First Posted: 2020-12-08
• Last Update Posted: 2020-12-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 57

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

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort A5; TAK-925 (Dose Level A5)	TAK-925	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.
Cohort A4; TAK-925 (Dose Level A4)	TAK-925	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.
Cohort A2; TAK-925 (Dose Level A2)	TAK-925	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.
Cohort A1; TAK-925 (Dose Level A1)	TAK-925	TAK-925, Dose Level A, once daily for up to 7 days in healthy participants.
Cohort A3; TAK-925 (Dose Level A3)	TAK-925	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.
Cohort B4; TAK-925 (Dose Level B4)	TAK-925	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.
Cohort C2; TAK-925 (Dose Level C2)	TAK-925	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.
Cohort A'1; TAK-925 (Dose Level A'1)	TAK-925	TAK-925, Dose Level A'1, single dose in healthy participants.
Cohort A6; TAK-925 (Dose Level A6)	TAK-925	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.
Cohort B3; TAK-925 (Dose Level B3)	TAK-925	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.
Part C (Cohorts C1-C2); TAK-925 Placebo	Placebo	TAK-925 Placebo, once daily for up to 7 days in participants with narcolepsy.
Part A (Cohorts A1-A6); TAK-925 Placebo	Placebo	TAK-925 Placebo, once daily for up to 7 days in healthy participants.
Cohort A'2; TAK-925 (Dose Level A'2)	TAK-925	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.
Cohort B1; TAK-925 (Dose Level B1)	TAK-925	TAK-925, Dose Level B1, once daily for up to 7 days in participants with narcolepsy.
Cohort C1; TAK-925 (Dose Level C1)	TAK-925	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.
Cohort B2; TAK-925 (Dose Level B2)	TAK-925	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.
Part B (Cohorts B1-B4); TAK-925 Placebo	Placebo	TAK-925 Placebo, once daily for up to 7 days in participants with narcolepsy.

Primary Outcome Measures

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

Name	Time	Method
Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925	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.
Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925	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.
Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925	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.
Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7	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.

Trial Locations

Locations (3)

PS Clinic; 🇯🇵 Fukuoka, Japan

Sumida Hospital; 🇯🇵 Sumida-ku, Tokyo, Japan

Hakata Clinic; 🇯🇵 Fukuoka, Japan