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)

• ClinicalTrials.gov Identifier: NCT04091425
• Recruitment Status: Completed
• First Posted: September 16, 2019
• Last Update Posted: April 20, 2020
• Sponsor: Millennium Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Takeda ( Millennium Pharmaceuticals, Inc. )

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 (Clinical Trial)
• 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: November 21, 2019
• Actual Primary Completion Date: April 2, 2020
• Actual Study Completion Date: April 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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Ceoi: Observed Plasma Concentration at the end of Infusion for TAK-925 [ Time Frame: 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 ]
2. AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-925 [ Time Frame: 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 ]
3. AUClast: Area Under the Plasma Concentration-Time Curve from Time 0 to Time of the Last Quantifiable Concentration for TAK-925 [ Time Frame: 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

• Ages Eligible for Study: 18 Years to 67 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Alabama

Wright Clinical Research

Alabaster, Alabama, United States, 35007

United States, Arizona

Pulmonary Associates Clinical Trials

Glendale, Arizona, United States, 85306

United States, Arkansas

Preferred Research Partners, Inc.

Little Rock, Arkansas, United States, 72211

United States, California

Stanford School of Medicine

Redwood City, California, United States, 94063

Pacific Research Network, Inc

San Diego, California, United States, 92103

United States, Colorado

Delta Waves Sleep Disorders and Research Center

Colorado Springs, Colorado, United States, 80918

United States, Florida

MD Clinical

Hallandale Beach, Florida, United States, 33009

Research Centers of America

Hollywood, Florida, United States, 33024

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States, 32216

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

Kissimmee, Florida, United States, 34741

Florida Pulmonary Research Institute, LLC

Winter Park, Florida, United States, 32789

United States, Georgia

NeuroTrials Research, Inc.

Atlanta, Georgia, United States, 30342

SleepCare Research Institute, Inc. d/b/a Clinical Research Institute

Stockbridge, Georgia, United States, 30281

United States, Maryland

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

Chevy Chase, Maryland, United States, 20815

United States, Ohio

CTI Clinical Trial and Consulting Services

Cincinnati, Ohio, United States, 45212

The Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

United States, South Carolina

Bogan Sleep Consultants, LLC

Columbia, South Carolina, United States, 29201

United States, Texas

Sleep Therapy & Research Center

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Director; Takeda

More Information

• Responsible Party: Millennium Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT04091425
• Other Study ID Numbers: TAK-925-2001
• First Posted: September 16, 2019
• Last Update Posted: April 20, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):

Drug therapy

Additional relevant MeSH terms:

Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Disorders of Excessive Somnolence; Sleepiness; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders