Clinical trial NCT03748979: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Narcolepsy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-11-21
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: From the first dose of study drug up to 7 days after the last dose of study drug (up to Day 15)
Secondary outcomes:
measure: Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925
timeFrame: 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
measure: Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925
timeFrame: 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
measure: Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925
timeFrame: 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
measure: Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7
timeFrame: Baseline, Day 1 and Day 7
Other outcomes:
Locations:
city: Sumida-ku
country: Japan
facility: Sumida Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Hakata Clinic
city: Fukuoka
country: Japan
facility: PS Clinic
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: