A Study of a Single Intravenous Infusion Dose of TAK-925 in Participants With Idiopathic Hypersomnia

A Phase 1b Randomized, Double-Blind, Placebo-Controlled, Crossover Study of a Single Intravenous Infusion Dose of TAK-925 in Patients With Idiopathic Hypersomnia

The purpose of this study is to evaluate the safety and tolerability of administering a single intravenous (IV) infusion dose of TAK-925 to adult participants with idiopathic hypersomnia (IH).

Study Overview

• Status: Completed
• Conditions: Idiopathic Hypersomnia
• Intervention / Treatment: Drug: TAK-925; Drug: TAK-925 Placebo

Detailed Description

The drug being tested in this study in participants with IH is called TAK-925. The study will have 2-treatment crossover groups. The study will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of a single intravenous (IV) dose of Dose A in participants with IH.

The study will enroll 40 patients. Participants will be randomly assigned to one of the two treatment sequence groups as indicated below:

• TAK-925 + Placebo
• Placebo + TAK-925

On Day 1 of each treatment period, TAK-925 or placebo will be administered as a single 9-hour IV infusion.

The multicenter study will be conducted in the United States and Japan. The overall duration of treatment in this study is approximately 41 days including screening up to 28 days, confinement for 6 days and end of study follow up telephone call on Study Day 11.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka-Ken
    • Hakata-ku, Fukuoka-Ken, Japan, 812-0025
      • SOUSEIKAI PS Clinic
  • Tokyo-To
    • Sumida-ku, Tokyo-To, Japan, 130-0004
      • Sumida Hospital
• United States
  • Alabama
    • Alabaster, Alabama, United States, 35007
      • Wright Clinical Research
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Pulmonary Associates Clinical Trials
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners, Inc.
  • California
    • Redwood City, California, United States, 94063
      • Stanford School of Medicine
    • San Diego, California, United States, 92103
      • Pacific Research Network, Inc
  • Colorado
    • Boulder, Colorado, United States, 80301
      • Alpine Clinical Research Center
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves Sleep Disorders and Research Center
  • Florida
    • Clearwater, Florida, United States, 33765
      • St Francis Medical Institute
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Hollywood, Florida, United States, 33024
      • Research Centers of America
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Kissimmee, Florida, United States, 34741
      • Pulmonary Disease Specialists, PA, d/b/a PDS Research
    • Winter Park, Florida, United States, 32789
      • Florida Pulmonary Research Institute, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • NeuroTrials Research, Inc.
    • Stockbridge, Georgia, United States, 30281
      • Global Research Associates
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Helene A. Emsellem, MD PC trading as "The Center for Sleep & Wake Disorders"
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Trial and Consulting Services
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Bogan Sleep Consultants, LLC
  • Texas
    • San Antonio, Texas, United States, 78229
      • Sleep Therapy & Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. A diagnosis of IH, as defined by the International Classification of Sleep Disorders-3 (ICSD-3) as verified by a previous nocturnal polysomnography (nPSG) and multiple sleep latency test (MSLT) study performed within the last 10 years.
2. Onset of hypersomnia between 10 and 30 years of age.
3. Seven consecutive days of actigraphy supported by a sleep diary obtained prior to the nPSG (Study Day -2) shows an average nightly sleep duration of greater than or equal to (>=) 420 minutes during the participant's normal nocturnal sleep period.
4. nPSG (Study Day -2) demonstrates that participant does not have other comorbid sleep disorders or clinically significant nocturnal hypoxemia (oxygen saturation ≤80% for ≥5% of total sleep time) and that their Apnea-Hypopnea Index (AHI) is less than or equal to (<=) 10 per hour, their periodic limb movement arousal index (PLMAI) <=15/hour, and that their total sleep time is >=6.5 hours.
5. Participants taking medication for treatment of excessive daytime sleepiness (EDS) must be willing to discontinue medication prior to randomization into the study.
6. Body mass index (BMI) of 18 through 33 kilogram per square meter (kg/m^2) inclusive.
7. Epworth Sleepiness Scale (ESS) score >=11 at screening and on Day -2.
8. Blood pressure (BP) must be <140 mmHg (systolic) and <90 mmHg (diastolic) at screening and Study Day -2.

Exclusion Criteria:

1. Average nightly sleep duration is <=8 hours (480 minutes) and has insufficient sleep syndrome as evidenced by sleeping >2 hours/night more on "off-days" relative to "work days" as determined by actigraphy and sleep diary obtained prior to the nPSG (Study Day -2).
2. Positive urine screen for drugs of abuse and/or positive alcohol test at screening and Study Day -2.
3. Resting heart rate (HR) outside of the range of 40 to 90 beats pper minute (bpm) off stimulants.
4. Screening electrocardiogram (ECG) reveals a QT interval with Fridericia correction method >450 ms (men) or >470 ms (women).
5. Usual bedtime later than 24:00 (midnight) or an occupation requiring nighttime shift work or variable shift work within the past 6 months, or travel with significant jet lag within 14 days before Study Day -2.
6. History of a sleep disorder other than IH, based on interviews at the screening visit, such as obstructive sleep apnea (OSA), restless legs syndrome, or periodic limb movements of sleep (PLMS) associated with arousals.
7. Use of any over-the-counter (OTC) or prescription medications with stimulating properties within 7 days prior to dosing or 5 half-lives (whichever is longer) that could affect the evaluation of EDS or use of sodium oxybate within 3 months of screening.
8. Nicotine dependence that is likely to have an effect on sleep (e.g., a participant who routinely awakens at night to smoke) and/or an unwillingness to discontinue all smoking and nicotine use during the confinement portion of the study (Day -2 to Day 4).
9. Caffeine consumption of more than 600 mg/day for 7 days before Study Day 1 (1 serving of coffee is approximately equivalent to 120 mg of caffeine) and/or unwilling to discontinue all caffeine during the confinement portion of the study (Day -2 to Day 4).
10. Alcohol use that is likely to have an effect on sleep and/or an unwillingness to discontinue all alcohol use from 72 hours before check-in through discharge on Study Day 4.
11. History of epilepsy or seizures, including having had a single seizure or a history of childhood febrile seizures or has a clinically significant history of head trauma.
12. Answered "YES" on Questions 4 or 5 on the Suicidal Ideation subscale of the Columbia Suicide Severity Rating Scale (C-SSRS) at screening (defined period as 3 months prior to screening) or evidence of suicidal behavior within 6 months of screening as measured by the Suicidal Behavior subscale of the C-SSRS.
13. Diagnosis of major depressive disorder (DSM-5), within the past 6 months or Beck Depression Inventory II (BDI-II) total score of >16 at the screening visit.
14. History of cerebral ischemia, transient ischemic attack, intracranial aneurysm, or arteriovenous malformation.
15. Known coronary artery disease, a history of myocardial infarction, angina, cardiac rhythm abnormality, or heart failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAK-925 Dose A + Placebo; TAK-925 112 milligram (mg), 9-hour intravenous infusion once on Day 1, Treatment Period 1 followed by 24 hours wash-out period, followed by TAK-925 placebo-matching 9-hour intravenous infusion once on Day 3, Treatment Period 2.	Drug: TAK-925; TAK-925 IV infusion.; Drug: TAK-925 Placebo; TAK-925 placebo-matching IV infusion.
Placebo Comparator: Placebo + TAK-925 Dose A; TAK-925 placebo-matching 9-hour intravenous infusion once on Day 1, Treatment Period 1 followed by 24 hours wash-out period, followed by, TAK-925 112 mg, 9-hour intravenous infusion once on Day 3, Treatment Period 2.	Drug: TAK-925; TAK-925 IV infusion.; Drug: TAK-925 Placebo; TAK-925 placebo-matching IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)	Study Day 1 up to Study Day 11
Percentage of Participants With Markedly Abnormal Criteria for Clinical Safety Laboratory Tests	Study Day 1 up to Study Day 11
Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements	From Predose up to Study Day 4
Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters	Study Day 1 up to Study Day 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925	Treatment Periods 1 and 2: Study Day 1 pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925	Treatment Periods 1 and 2: Study Day 1 pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion
AUC Last: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-925	Treatment Periods 1 and 2: Study Day 1 pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.
• Investigators: Study Director: Study Director, Takeda

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2020
• Primary Completion (Actual): November 19, 2020
• Study Completion (Actual): November 23, 2020

Study Registration Dates

• First Submitted: September 13, 2019
• First Submitted That Met QC Criteria: September 13, 2019
• First Posted (Actual): September 16, 2019

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disorders of Excessive Somnolence; Idiopathic Hypersomnia
• Other Study ID Numbers: TAK-925-2002; U1111-1238-3314 (Registry Identifier: WHO); JapicCTI-195087 (Registry Identifier: JapicCTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No