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

Healthy Participants Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03748979
• Other study ID #: TAK-925-1003
• Secondary ID: U1111-1221-3144J
• Status: Completed
• Phase: Phase 1
• Start date: November 21, 2018
• Est. completion date: October 24, 2019

Study information

• Verified date: December 2020
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: October 24, 2019
• Est. primary completion date: October 24, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Participants
• Narcolepsy

Intervention

Drug:
• TAK-925
TAK-925
• Placebo
TAK-925 Placebo

Locations

Country	Name	City	State
Japan	Hakata Clinic	Fukuoka
Japan	PS Clinic	Fukuoka
Japan	Sumida Hospital	Sumida-ku	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the first dose of study drug up to 7 days after the last dose of study drug (up to Day 15)
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	Baseline, Day 1 and Day 7