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

• Sponsor: Millennium Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04091438
• Collaborator: (none)
• Enrollment: 28
• Locations: 22
• Arms: 2
• Actual Duration (Months): 10
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Hypersomnia	Drug: TAK-925; Drug: TAK-925 Placebo	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1b Randomized, Double-Blind, Placebo-Controlled, Crossover Study of a Single Intravenous Infusion Dose of TAK-925 in Patients With Idiopathic Hypersomnia
• Actual Study Start Date: Jan 26, 2020
• Actual Primary Completion Date: Nov 25, 2020
• Actual Study Completion Date: Nov 25, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAK-925 Dose A + Placebo TAK-925 Dose A, 9-hour IV infusion once on Day 1, Treatment Period 1 followed by 24 hours wash-out period, followed by TAK-925 placebo-matching 9-hour IV 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 IV infusion once on Day 1, Treatment Period 1 followed by 24 hours wash-out period, followed by, TAK-925 Dose A, 9-hour IV 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.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants who Experience at Least One Treatment Emergent Adverse Event (TEAE) [Baseline up to 7 days after the last dose of study drug (Up to Day 11)]

   An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an AE with an onset that occurs after receiving study drug.

2. Percentage of Participants who Meet the Markedly Abnormal Criteria for Clinical Safety Laboratory Tests at Least Once Post a Regimen [Baseline up to Day 4]

   Clinical laboratory evaluations include hematology, blood chemistry, and urinalysis.

3. Percentage of Participants who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post a Regimen [Baseline up to Day 4]

   Vital signs include body temperature, respiratory rate, systolic and diastolic blood pressure and heart rate.

4. Percentage of Participants who Meet the Markedly Abnormal Criteria for 12-Lead Safety Electrocardiogram (ECG) Parameters at Least Once Post a Regimen [Baseline up to Day 4]

   A standard 12-lead ECG will be performed.

Secondary Outcome Measures

1. Ceoi: Observed Plasma Concentration at the end of Infusion for TAK-925 [Periods 1 and 2: 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]

2. AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-925 [Periods 1 and 2: 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]

3. AUC last: Area Under the Plasma Concentration-Time Curve from Time 0 to Time of the Last Quantifiable Concentration for TAK-925 [Periods 1 and 2: 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Millennium Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Millennium Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT04091438
• Other Study ID Numbers: TAK-925-2002; U1111-1238-3314; JapicCTI-195087
• First Posted: Sep 16, 2019
• Last Update Posted: Mar 8, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Millennium Pharmaceuticals, Inc.: Drug therapy
• Additional relevant MeSH terms: Disorders of Excessive Somnolence; Idiopathic Hypersomnia

Study Results

No Results Posted as of Mar 8, 2021