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

NCT03332784 | Completed Phase 1 Results

• 3 other identifiers: TAK-925-1001U1111-1201-6634JapicCTI-173756
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 3

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.

Conditions

Healthy Participants and Patients With Narcolepsy

Outcome Measures

Primary Outcomes (27)

• Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

  Baseline up to Day 7

• Number of Participants Who Experience at Least One TEAE Related to Vital Signs

  Baseline up to Day 7

• Number of Participants Who Experience at Least One TEAE Related to Body Weight

  Baseline up to Day 7

• Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)

  Baseline up to Day 7

• Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests

  Baseline up to Day 7

• 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

  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

• 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

  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

• Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2

  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

• Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2

  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

• Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2

  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

• Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2

  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

• Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2

  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

• Part 2, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2

  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

• Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2

  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

• Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2

  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

• Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2

  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

• Part 2, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2

  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

• Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925

  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

• Part 2, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925

  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

• Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925

  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

• Part 2, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925

  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

• Part 1, CL: Total Clearance After Intravenous Administration for TAK-925

  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

• Part 2, CL: Total Clearance After Intravenous Administration for TAK-925

  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

• Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24

  Urine assessments were done only in Part 1, as planned.

  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

• 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

  Urine assessments were done only in Part 1, as planned.

  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

• Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2

  Urine assessments were done only in Part 1, as planned.

  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

• 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

  Day 1 at 6 hours after start of infusion

Secondary Outcomes (1)

• Part 2: Average Sleep Latency in Maintenance of Wakefulness Test (MWT)

  Days 1 and 3 up to 8 hours following the start of infusion

Study Arms (14)

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

EXPERIMENTAL

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

Drug: TAK-925

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

EXPERIMENTAL

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.

Drug: TAK-925

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

EXPERIMENTAL

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.

Drug: TAK-925

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

EXPERIMENTAL

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.

Drug: TAK-925

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

EXPERIMENTAL

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.

Drug: TAK-925

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

EXPERIMENTAL

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.

Drug: TAK-925

Part 1: Placebo (Cohort 1-2)

PLACEBO COMPARATOR

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

Drug: Placebo

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

EXPERIMENTAL

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.

Drug: TAK-925

Part 1: Placebo (Cohort 3)

PLACEBO COMPARATOR

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

Drug: Placebo

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

EXPERIMENTAL

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.

Drug: TAK-925

Part 2: TAK-925 TBD (Cohort 5)

EXPERIMENTAL

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).

Drug: TAK-925

Part 2: TAK-925 TBD (Cohort 6)

EXPERIMENTAL

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).

Drug: TAK-925

Part 2: TAK-925 TBD (Cohort 7)

EXPERIMENTAL

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).

Drug: TAK-925

Part 2: Placebo (Cohort 5-7)

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

TAK-925 DRUG

TAK-925 Intravenous Infusion

Part 1: TAK-925 (Cohort 1; Dose Level 1); Part 1: TAK-925 (Cohort 1; Dose Level 3); Part 1: TAK-925 (Cohort 1; Dose Level 5); Part 1: TAK-925 (Cohort 2; Dose Level 2); Part 1: TAK-925 (Cohort 2; Dose Level 4); Part 1: TAK-925 (Cohort 2; Dose Level 6); Part 1: TAK-925 (Cohort 3; Dose Level 5); Part 1: TAK-925 (Cohort 4; Dose Level 5); Part 2: TAK-925 TBD (Cohort 5); Part 2: TAK-925 TBD (Cohort 6); Part 2: TAK-925 TBD (Cohort 7)

Placebo DRUG

TAK-925 Placebo Intravenous Infusion

Part 1: Placebo (Cohort 1-2); Part 1: Placebo (Cohort 3); Part 2: Placebo (Cohort 5-7)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (3)

Sumida Hospital

Sumida-ku, Tokyo, Japan

Location

Hakata Clinic

Fukuoka, Japan

Location

PS Clinic

Fukuoka, Japan

Location

MeSH Terms

Interventions

TAK-925

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2017
• First Posted: November 6, 2017
• Study Start: November 4, 2017
• Primary Completion: September 4, 2018
• Study Completion: September 4, 2018
• Last Updated: March 30, 2021
• Results First Posted: November 18, 2020

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

JP (3)