Phase 1 TAK-925 Study in Healthy Adult and Elderly Volunteers and Participants With Narcolepsy

NCT ID: NCT03332784

Last Updated: 2021-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-04
• Study Completion Date: 2018-09-04

Brief Summary

The purpose of this study is to investigate safety, tolerability, and pharmacokinetics of TAK-925 when a single dose of TAK-925 is administered to healthy adult participants, healthy elderly participants and patients with type 1 narcolepsy.

Detailed Description

Orexins are neuropeptides that play a role in the regulation of sleep and wakefulness. In type 1 narcolepsy, there is a loss of orexin producing neurons in the brain. The investigational drug, TAK-925, is an orexin 2 receptor agonist that is being tested in healthy adult participants, healthy elderly participants and patients with narcolepsy in order to evaluate the safety, tolerability, and pharmacokinetics (PK) of a single intravenous administration.

The study will enroll approximately 20 healthy participants and 16 healthy elderly participants in Part 1 of the study and approximately 20 patients with narcolepsy in Part 2.

In Part 1, the study consists of 4 cohorts of 8 or 4 participants each. Participants will be randomly assigned (by chance, like flipping a coin) to one of the following treatment groups to receive TAK-925 or placebo:

• Part 1, Cohort 1; TAK-925 (Dose Level 1, 3, 5), Cohort 2; TAK-925 (Dose Level 2, 4, 6), Cohort 3 and 4; TAK-925 (Dose Level 5)

For Cohort 1-4, healthy adult and elderly participants will be administered TAK-925 or placebo once in each cohort or dose level. The dose at the start (Cohort 1 dose level 1) is 7 mg of TAK-925 and following doses in Cohorts 1-4 will be determined based on available data from previous Cohorts/dose levels.

In Part 2 of the study, the study consists of 3 cohorts of 4 to 12 patients with narcolepsy. Patients will be randomly assigned to one of the treatment groups of Cohort 5-7 and will be administered TAK-925 or placebo once in each cohort. The dose of TAK-925 in Cohort 5-7 is TBD and will be decided based on available data from Part 1 and previous Cohorts.

• Part 2, Cohort 5-7

This multi-center trial will be conducted in Japan. Participants will make multiple visits to the clinic. Visits in Part 1 will include a screening period (Day -28 to -2), Check-in on Day -1, Treatment period (Day 1 and 2), and follow-up visit on Day 7. In Part 2 of the study, the visits include a screening period (Day -42 to -2), Check-in on Day -1, Cross-over period (Day 1 to 4), and follow-up visit on Day 7.

Conditions

Healthy Participants and Patients With Narcolepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Part 1: TAK-925 (Cohort 1; Dose Level 1)

TAK-925, Intravenous single administration. Healthy adults will be enrolled in double blind manner.

Group Type: EXPERIMENTAL

TAK-925

Intervention Type: DRUG

TAK-925 Intravenous Infusion

Part 1: TAK-925 (Cohort 2; Dose Level 2)

TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 2). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.

Group Type: EXPERIMENTAL

TAK-925

Intervention Type: DRUG

TAK-925 Intravenous Infusion

Part 1: TAK-925 (Cohort 1; Dose Level 3)

TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 3). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.

Group Type: EXPERIMENTAL

TAK-925

Intervention Type: DRUG

TAK-925 Intravenous Infusion

Part 1: TAK-925 (Cohort 2; Dose Level 4)

TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 4). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.

Group Type: EXPERIMENTAL

TAK-925

Intervention Type: DRUG

TAK-925 Intravenous Infusion

Part 1: TAK-925 (Cohort 1; Dose Level 5)

TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.

Group Type: EXPERIMENTAL

TAK-925

Intervention Type: DRUG

TAK-925 Intravenous Infusion

Part 1: TAK-925 (Cohort 2; Dose Level 6)

TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 6). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.

Group Type: EXPERIMENTAL

TAK-925

Intervention Type: DRUG

TAK-925 Intravenous Infusion

Part 1: Placebo (Cohort 1-2)

TAK-925 Placebo, Intravenous single administration. Healthy adults will be enrolled in double blind manner.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

TAK-925 Placebo Intravenous Infusion

Part 1: TAK-925 (Cohort 3; Dose Level 5)

TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Healthy elderly participants will be enrolled in double blind manner.

Group Type: EXPERIMENTAL

TAK-925

Intervention Type: DRUG

TAK-925 Intravenous Infusion

Part 1: Placebo (Cohort 3)

TAK-925 Placebo, Intravenous single administration. Healthy elderly participants will be enrolled in double blind manner.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

TAK-925 Placebo Intravenous Infusion

Part 1: TAK-925 (Cohort 4; Dose Level 5)

TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Healthy adults will be enrolled in non-blinded manner.

Group Type: EXPERIMENTAL

TAK-925

Intervention Type: DRUG

TAK-925 Intravenous Infusion

Part 2: TAK-925 TBD (Cohort 5)

TAK-925, Intravenous single administration. Dose in Cohort 5 will be based on safety and tolerability in the Part 1. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).

Group Type: EXPERIMENTAL

TAK-925

Intervention Type: DRUG

TAK-925 Intravenous Infusion

Part 2: TAK-925 TBD (Cohort 6)

TAK-925, Intravenous single administration. Dose in Cohort 6 TBD based on safety, tolerability, PK data, and results of the Maintenance Wakefulness Test (MWT) from previous Cohorts. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).

Group Type: EXPERIMENTAL

TAK-925

Intervention Type: DRUG

TAK-925 Intravenous Infusion

Part 2: TAK-925 TBD (Cohort 7)

TAK-925, Intravenous single administration. Dose in Cohort 7 TBD based on safety, tolerability, PK data, and results of the Maintenance of Wakefulness Test (MWT) from previous Cohorts. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).

Group Type: EXPERIMENTAL

TAK-925

Intervention Type: DRUG

TAK-925 Intravenous Infusion

Part 2: Placebo (Cohort 5-7)

TAK-925 Placebo, Intravenous single administration. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

TAK-925 Placebo Intravenous Infusion

Interventions

TAK-925

TAK-925 Intravenous Infusion

Intervention Type: DRUG

Placebo

TAK-925 Placebo Intravenous Infusion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Healthy adult participants and Healthy elderly participants:

• Participant weighs at least 50 kilogram (kg) (Healthy adults participants) / 40 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 patients:

• Patient weighs at least 40 kg inclusive at Screening.
• A diagnosis of narcolepsy Type 1, as defined by the International Classification of Sleep Disorders, Third Edition (ICSD-3).
• HLA narcolepsy test positivity.
• At Day -1, Epworth sleepiness scale (ESS) score greater than or equal to (>=) 10
• Blood pressure less than (<) 140 systolic and < 90 diastolic. The patient may have a history of hypertension and be on antihypertensive medication treatment as long as the BP meets these criteria.

Exclusion Criteria

All Participants:

• Participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 2 years prior to the Screening visit.
• Past or current epilepsy, convulsion, tremor or the disorders of related symptoms.
• Has a lifetime history of major psychiatric disorder, such as major depressive disorder, bipolar disorder, or schizophrenia.

HV (only Cohort 4):

• Participant has had CSF collection performed within 14 days prior to check-in (Day -1).

Narcolepsy patients

• Medical disorder associated with excessive sleepiness other than narcolepsy (including sleep apnea syndrome).
• Excessive caffeine (greater than [>] 400 milligram per day [mg/day]) use one week prior to study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Sumida Hospital

Sumida-ku, Tokyo, Japan

Hakata Clinic

Fukuoka, , Japan

PS Clinic

Fukuoka, , Japan

Countries

Japan

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1201-6634

Identifier Type: OTHER

Identifier Source: secondary_id

JapicCTI-173756

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-925-1001

Identifier Type: -

Identifier Source: org_study_id