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

NCT ID: NCT04091438

Last Updated: 2023-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-26
• Study Completion Date: 2020-11-23

Brief Summary

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).

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.

Conditions

Idiopathic Hypersomnia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

TAK-925

Intervention Type: DRUG

TAK-925 IV infusion.

TAK-925 Placebo

Intervention Type: DRUG

TAK-925 placebo-matching IV infusion.

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.

Group Type: PLACEBO_COMPARATOR

TAK-925

Intervention Type: DRUG

TAK-925 IV infusion.

TAK-925 Placebo

Intervention Type: DRUG

TAK-925 placebo-matching IV infusion.

Interventions

TAK-925

TAK-925 IV infusion.

Intervention Type: DRUG

TAK-925 Placebo

TAK-925 placebo-matching IV infusion.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Wright Clinical Research

Alabaster, Alabama, United States

Pulmonary Associates Clinical Trials

Glendale, Arizona, United States

Preferred Research Partners, Inc.

Little Rock, Arkansas, United States

Stanford School of Medicine

Redwood City, California, United States

Pacific Research Network, Inc

San Diego, California, United States

Alpine Clinical Research Center

Boulder, Colorado, United States

Delta Waves Sleep Disorders and Research Center

Colorado Springs, Colorado, United States

St Francis Medical Institute

Clearwater, Florida, United States

MD Clinical

Hallandale, Florida, United States

Research Centers of America

Hollywood, Florida, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Pulmonary Disease Specialists, PA, d/b/a PDS Research

Kissimmee, Florida, United States

Florida Pulmonary Research Institute, LLC

Winter Park, Florida, United States

NeuroTrials Research, Inc.

Atlanta, Georgia, United States

Global Research Associates

Stockbridge, Georgia, United States

Helene A. Emsellem, MD PC trading as "The Center for Sleep & Wake Disorders"

Chevy Chase, Maryland, United States

CTI Clinical Trial and Consulting Services

Cincinnati, Ohio, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Bogan Sleep Consultants, LLC

Columbia, South Carolina, United States

Sleep Therapy & Research Center

San Antonio, Texas, United States

SOUSEIKAI PS Clinic

Hakata-ku, Fukuoka, Japan

Sumida Hospital

Sumida-ku, Tokyo-To, Japan

Countries

United States; Japan

References

Mignot E, Bogan RK, Emsellem H, Foldvary-Schaefer N, Naylor M, Neuwirth R, Faessel H, Swick T, Olsson T. Safety and pharmacodynamics of a single infusion of danavorexton in adults with idiopathic hypersomnia. Sleep. 2023 Sep 8;46(9):zsad049. doi: 10.1093/sleep/zsad049.

Reference Type: DERIVED

PMID: 36883238 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1238-3314

Identifier Type: REGISTRY

Identifier Source: secondary_id

JapicCTI-195087

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-925-2002

Identifier Type: -

Identifier Source: org_study_id