Study of TAK-925 in Participants With Obstructive Sleep Apnea (OSA) Who Are Experiencing Excessive Daytime Sleepiness (EDS) Despite Adequate Use of Continuous Positive Airway Pressure (CPAP)

Sponsor

Millennium Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT04091425

Collaborator

(none)

Enrollment

Locations

Arms

4.4

Actual Duration (Months)

1.4

Patients Per Site

0.3

Patients Per Site Per Month

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 adults with obstructive sleep apnea (OSA) who are experiencing excessive daytime sleepiness (EDS) despite adequate use of CPAP as the primary OSA therapy.

Condition or Disease	Intervention/Treatment	Phase
Obstructive Sleep Apnea	Drug: TAK-925 Drug: Placebo	Phase 1

Detailed Description

The drug being tested in this study is called TAK-925. TAK-925 is being tested to treat participants who have EDS due to OSA despite using CPAP. The study will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of a single IV dose of TAK-925 in participants with OSA.

The study will enroll approximately 42 patients. The study will utilize a three-way cross over design with a 24 hour wash-out between each treatment.

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

The multi-center study will be conducted in United States. The patient's participation in the study will last for up to 43 days and include an 8-day stay in the study clinic and a safety follow-up phone call 7 days after the end of treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

25 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 2 Single Intravenous Infusion Doses of TAK-925 in Subjects With Obstructive Sleep Apnea Who Are Experiencing Excessive Daytime Sleepiness Despite Adequate Use of CPAP

Actual Study Start Date :

Nov 21, 2019

Actual Primary Completion Date :

Apr 2, 2020

Actual Study Completion Date :

Apr 2, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAK-925 Dose A TAK-925 dose A intravenous (IV) infusion in each treatment sequence (crossover design).	Drug: TAK-925 TAK-925 IV infusion
Experimental: TAK-925 Dose B TAK-925 dose B IV infusion in each treatment sequence (cross over design).	Drug: TAK-925 TAK-925 IV infusion
Placebo Comparator: Placebo TAK-925 placebo-matching IV infusion in each treatment sequence (crossover design).	Drug: Placebo TAK-925 placebo-matching IV infusion

Arm

Intervention/Treatment

Experimental: TAK-925 Dose A

TAK-925 dose A intravenous (IV) infusion in each treatment sequence (crossover design).

Drug: TAK-925

TAK-925 IV infusion

Experimental: TAK-925 Dose B

TAK-925 dose B IV infusion in each treatment sequence (cross over design).

Drug: TAK-925

TAK-925 IV infusion

Placebo Comparator: Placebo

TAK-925 placebo-matching IV infusion in each treatment sequence (crossover design).

Drug: Placebo

TAK-925 placebo-matching IV infusion

Outcome Measures

Primary Outcome Measures

Percentage of Participants who Experience at Least One Treatment Emergent Adverse Event (TEAE) [Up to approximately 43 days]
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.
Percentage of Participants who Meet the Markedly Abnormal Criteria for Clinical Safety Laboratory Tests at Least Once Post a Regimen [Up to approximately 43 days]
Clinical laboratory evaluations include hematology, blood chemistry, and urinalysis.
Percentage of Participants who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post a Regimen [Up to approximately 43 days]
Vital signs include heart rate, respiratory rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Percentage of Participants who Meet the Markedly Abnormal Criteria for 12-Lead Safety Electrocardiogram (ECG) Parameters at Least Once Post a Regimen [Up to approximately 43 days]
A standard 12-lead ECG will be performed.

Secondary Outcome Measures

Ceoi: Observed Plasma Concentration at the end of Infusion for TAK-925 [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 on Day 1 each Treatment Period]
AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-925 [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 on Day 1 each Treatment Period]
AUClast: Area Under the Plasma Concentration-Time Curve from Time 0 to Time of the Last Quantifiable Concentration for TAK-925 [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 on Day 1 of each Treatment Period]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 67 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Has OSA diagnosed according to the international classification of sleep disorders-3 (ICSD-3) criteria and with current use of CPAP.
Has a complaint of EDS despite "consistent use" of CPAP as defined by machine tracking time as having at least 4 hours of CPAP use/night on at least 70% during the approximately 1 month before randomization.
If taking a stimulant medication for the treatment of excessive daytime sleepiness must be willing to discontinue medication before randomization into the study.
Has a regular bedtime between 21:00 and 24:00 as verified by history and regular time in bed averaging between 7.5 and 9.0 hours/night and gets at least 6.5 hours/night on average of sleep, as defined by approximately 7 days of actigraphy supported by a sleep diary, which are completed at least 1 week before Study Day-2.
Has a Epworth sleepiness scale (ESS) score of ≥10 at screening and Study Day -2, with or without stimulants.
Nocturnal polysomnography (NPSG) demonstrates that the participant does not have other comorbid sleep disorders or clinically significant nocturnal hypoxemia (O2 saturation ≤80% for ≥5% of total sleep time) and that their apnea-hypopnea index (AHI) is ≤10.
Has an average (of 4 sessions) baseline MWT sleep latency less than or equal to 20 minutes and no single session has a sleep latency of greater than 30 minutes as determined by the site investigator.

Exclusion Criteria:

Has supine or standing average systolic blood pressure (SBP) ≥140 millimeters of mercury (mm Hg) or average diastolic blood pressure (DBP) ≥90 mm Hg at screening or Study Day-2; blood pressures will be averaged over 3 readings done 10 minutes (min) apart.
A screening electrocardiogram (ECG) reveals a QT interval with Fridericia correction method >450 milliseconds (ms) (men) or >470 ms (women).
Has a usual bedtime later than 01:00 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.
Short sleepers with chronic sleep deprivation who get on average less than 7.5 hours/night time in bed and/or less than 6.5 hours of sleep per night as defined by approximately 1 week of nocturnal actigraphy testing and supported by a sleep diary, both of which are completed at least 1 week before Study Day -2 admission to the clinical unit.
Has a history of a sleep disorder other than OSA that is associated with EDS on the basis of interviews at the screening visit, such as, for example, restless legs syndrome, confirmed by prior pretreatment polysomnography (PSG) data demonstrating periodic limb movement during sleep (PLMS) >15.
Has used any over-the-counter (OTC) or prescription medications with stimulating properties within 7 days before dosing or 5 half-lives (whichever is longer) that could affect the evaluation of EDS or any use of sodium oxybate within 3 months of screening.
Has nicotine dependence that is likely to have an effect on sleep (e.g., a participant who routinely awakens at night to smoke) or challenge the conduct of this study (smokes ≥10 cigarettes/day) and/or the participant is unwilling to discontinue all smoking and nicotine use during the study.
Has a 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).
History or presence of any acutely unstable medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or surgical history that could affect the safety of the subject or interfere with study efficacy, safety, PK assessments, or the ability of the subject to complete the study per the judgment of the investigator.

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	Delta Waves Sleep Disorders and Research Center	Colorado Springs	Colorado	United States	80918
7	MD Clinical	Hallandale Beach	Florida	United States	33009
8	Research Centers of America	Hollywood	Florida	United States	33024
9	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
10	Pulmonary Disease Specialists, PA, d/b/a PDS Research	Kissimmee	Florida	United States	34741
11	Florida Pulmonary Research Institute, LLC	Winter Park	Florida	United States	32789
12	NeuroTrials Research, Inc.	Atlanta	Georgia	United States	30342
13	SleepCare Research Institute, Inc. d/b/a Clinical Research Institute	Stockbridge	Georgia	United States	30281
14	Helene A. Emsellem, MD PC trading as "The Center for Sleep & Wake Disorders"	Chevy Chase	Maryland	United States	20815
15	CTI Clinical Trial and Consulting Services	Cincinnati	Ohio	United States	45212
16	The Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
17	Bogan Sleep Consultants, LLC	Columbia	South Carolina	United States	29201
18	Sleep Therapy & Research Center	San Antonio	Texas	United States	78229