Clinical trial NCT03332784: Phase 1 TAK-925 Study in Healthy Adult and Elderly Volunteers and Participants With Narcolepsy
Official title: A Phase 1 Study of TAK-925 to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Dose of TAK-925 in Healthy Adult and Elderly Volunteers and Patients With Narcolepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants and Patients With Narcolepsy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-11-06
Enrollment: 58
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: OTHER

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.

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.

Primary outcomes:
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Day 7
measure: Number of Participants Who Experience at Least One TEAE Related to Vital Signs
timeFrame: Baseline up to Day 7
measure: Number of Participants Who Experience at Least One TEAE Related to Body Weight
timeFrame: Baseline up to Day 7
measure: Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)
timeFrame: Baseline up to Day 7
measure: Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests
timeFrame: Baseline up to Day 7
measure: Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2
timeFrame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
measure: Part 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2
timeFrame: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
measure: Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2
timeFrame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
measure: Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2
timeFrame: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
measure: Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2
timeFrame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
measure: Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2
timeFrame: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
measure: Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2
timeFrame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
measure: Part 2, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2
timeFrame: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
measure: Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2
timeFrame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
measure: Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2
timeFrame: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
measure: Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2
timeFrame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
measure: Part 2, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2
timeFrame: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
measure: Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925
timeFrame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
measure: Part 2, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925
timeFrame: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
measure: Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925
timeFrame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
measure: Part 2, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925
timeFrame: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
measure: Part 1, CL: Total Clearance After Intravenous Administration for TAK-925
timeFrame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
measure: Part 2, CL: Total Clearance After Intravenous Administration for TAK-925
timeFrame: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
measure: Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24
timeFrame: Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion
measure: Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2
timeFrame: Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion
measure: Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2
timeFrame: Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6 and 6-15 hours post-infusion
measure: Part 1, R(CSF/Plasma,ss): Cerebrospinal Fluid/Plasma Drug Concentration at Steady State for TAK-925 and Its Metabolites M1 and M2 in Cohort 4
timeFrame: Day 1 at 6 hours after start of infusion
Secondary outcomes:
measure: Part 2: Average Sleep Latency in Maintenance of Wakefulness Test (MWT)
timeFrame: Days 1 and 3 up to 8 hours following the start of infusion
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: Study Director
role: STUDY_DIRECTOR
References: