Study of TAK-925 in Participants With Obstructive Sleep Apnea (OSA) Who Are Experiencing Excessive Daytime Sleepiness (EDS) Despite Current or Prior Use of a Primary OSA Therapy

• ClinicalTrials.gov Identifier: NCT04091425
• Recruitment Status: Not yet recruiting
• First Posted: September 16, 2019
• Last Update Posted: September 16, 2019
• 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 current use of continuous positive airway pressure (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 overall duration of this study is approximately 43 days. Participants will make multiple visits to the clinic and will be followed up for 7 days after the end of treatment for safety follow-up.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 42 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 Current or Prior Use of a Primary Obstructive Sleep Apnea Therapy
• Estimated Study Start Date: October 26, 2019
• Estimated Primary Completion Date: March 24, 2020
• Estimated Study Completion Date: March 24, 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 3 weeks 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 systolic blood pressure (SBP) ≥160 mm Hg or diastolic blood pressure (DBP) ≥100 mm Hg at screening or Study Day 1.
• 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

Contacts

Contact: Takeda Study Registration Call Center; 877-825-3327 ext +1; medicalinformation@tpna.com

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Director; Takeda

More Information

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

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; Sleepiness; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases