Clinical trial NCT04091425: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Obstructive Sleep Apnea
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-09-16
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 67
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants who Experience at Least One Treatment Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 43 days
measure: Percentage of Participants who Meet the Markedly Abnormal Criteria for Clinical Safety Laboratory Tests at Least Once Post a Regimen
timeFrame: Up to approximately 43 days
measure: Percentage of Participants who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post a Regimen
timeFrame: Up to approximately 43 days
measure: Percentage of Participants who Meet the Markedly Abnormal Criteria for 12-Lead Safety Electrocardiogram (ECG) Parameters at Least Once Post a Regimen
timeFrame: Up to approximately 43 days
Secondary outcomes:
measure: Ceoi: Observed Plasma Concentration at the end of Infusion for TAK-925
timeFrame: 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
measure: AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-925
timeFrame: 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
measure: AUClast: Area Under the Plasma Concentration-Time Curve from Time 0 to Time of the Last Quantifiable Concentration for TAK-925
timeFrame: 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
Other outcomes:
Locations:
city: Alabaster
country: United States
facility: Wright Clinical Research
state: Alabama
city: Glendale
country: United States
facility: Pulmonary Associates Clinical Trials
state: Arizona
city: Little Rock
country: United States
facility: Preferred Research Partners, Inc.
state: Arkansas
city: Redwood City
country: United States
facility: Stanford School of Medicine
state: California
city: San Diego
country: United States
facility: Pacific Research Network, Inc
state: California
city: Colorado Springs
country: United States
facility: Delta Waves Sleep Disorders and Research Center
state: Colorado
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Kissimmee
country: United States
facility: Pulmonary Disease Specialists, PA, d/b/a PDS Research
state: Florida
city: Winter Park
country: United States
facility: Florida Pulmonary Research Institute, LLC
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research, Inc.
state: Georgia
city: Stockbridge
country: United States
facility: SleepCare Research Institute, Inc. d/b/a Clinical Research Institute
state: Georgia
city: Chevy Chase
country: United States
facility: Helene A. Emsellem, MD PC trading as "The Center for Sleep & Wake Disorders"
state: Maryland
city: Cincinnati
country: United States
facility: CTI Clinical Trial and Consulting Services
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbia
country: United States
facility: Bogan Sleep Consultants, LLC
state: South Carolina
city: San Antonio
country: United States
facility: Sleep Therapy & Research Center
state: Texas
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: