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

Takeda

Status and phase

Completed

Phase 1

Conditions

Healthy Participants and Patients With Narcolepsy

Treatments

Drug: TAK-925

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT03332784

U1111-1201-6634 (Other Identifier)

JapicCTI-173756 (Registry Identifier)

TAK-925-1001

Details and patient eligibility

About

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.

Full 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.

Enrollment

58 patients

Sex

All

Ages

18 to 80 years old

Volunteers

Accepts Healthy Volunteers

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.

Trial design

Primary purpose

Other

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

Double Blind

58 participants in 14 patient groups, including a placebo group

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

Experimental group

Description:

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

Treatment:

Drug: TAK-925

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

Experimental group

Description:

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.

Treatment:

Drug: TAK-925

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

Experimental group

Description:

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.

Treatment:

Drug: TAK-925

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

Experimental group

Description:

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.

Treatment:

Drug: TAK-925

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

Experimental group

Description:

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.

Treatment:

Drug: TAK-925

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

Experimental group

Description:

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.

Treatment:

Drug: TAK-925

Part 1: Placebo (Cohort 1-2)

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

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

Experimental group

Description:

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.

Treatment:

Drug: TAK-925

Part 1: Placebo (Cohort 3)

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

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

Experimental group

Description:

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.

Treatment:

Drug: TAK-925

Part 2: TAK-925 TBD (Cohort 5)

Experimental group

Description:

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).

Treatment:

Drug: TAK-925

Part 2: TAK-925 TBD (Cohort 6)

Experimental group

Description:

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).

Treatment:

Drug: TAK-925

Part 2: TAK-925 TBD (Cohort 7)

Experimental group

Description:

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).

Treatment:

Drug: TAK-925

Part 2: Placebo (Cohort 5-7)

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Trial documents