A Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics (PK) of Oral TAK-994 in an Acute Sleep Phase Delay Paradigm in Healthy Male Participants

A Randomized, Double-Blind, Placebo-Controlled, 3-Period Crossover Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Oral TAK-994 in an Acute Sleep Phase Delay Paradigm in Healthy Male Subjects

The purpose of this study is to assess the safety and tolerability of TAK-994 and to determine the effect of TAK-994 (compared to placebo) on sleepiness, as measured by mean sleep latency on the maintenance of wakefulness Test (MWT), in an acute sleep phase delay paradigm in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TAK-994; Drug: Placebo

Detailed Description

The drug being tested in this study is called TAK-994. The study will evaluate the safety/tolerability, PD, and PK of TAK-994 in an acute sleep phase delay paradigm in healthy participants.

The study will enroll up to approximately 18 healthy participants. Participants will be randomly assigned to 1 of the 3 treatment sequences which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• TAK-994 Dose A + Placebo + TAK-994 Dose B
• TAK-994 Dose B + TAK-994 Dose A + Placebo
• Placebo + TAK-994 Dose B + TAK-994 Dose A

This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 10 weeks. Participants will be followed up remotely on Day 7 after the last dose of study drug for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10019
      • Clinilabs Drug Development Corporation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Be a current nonsmoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months prior to the first dose of study drug.
2. Have regular sleep-wake habits (example, routinely spending 6.5 to 8 hour sleeping nightly, not oversleeping by more than 3 hour on weekends [that is, total sleep not more than 11 hour]) as determined by investigator interviews and confirmed in 5-day actigraphy records and regularly fall asleep between 9:30 PM and 12:00 AM.

Exclusion Criteria:

1. Have a positive alcohol or drug screen or a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce] per day).
2. Have excessive sleepiness, defined by a self-reported Epworth Sleepiness Scale (ESS) score at screening greater than (>) 10; irregular work hours; or routine night-shift work within 1 month before randomization.
3. Have a prior history of or currently is experiencing any known/suspected sleep disorder (including obstructive sleep apnea and restless leg syndrome), any disorder associated with excessive daytime sleepiness (EDS), or any diagnosis interfering with assessment of sleepiness.
4. At the time of screening, be receiving treatment with nasal/oronasal positive airway pressure for any reason.
5. Have abnormal findings on the initial polysomnography conducted on Day -1 (check-in) of the first treatment period.
6. Have traveled across 2 or more time zones within the 2 weeks before screening.
7. Have caffeine consumption of more than 400 milligram (mg)/day for 2 weeks before screening (1 serving of coffee is approximately equivalent to 120 mg of caffeine).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAK-994 Dose A+ Placebo + TAK-994 Dose B; TAK-994 Dose A tablets, orally, on Days 1 and 2 of Treatment Period 1, followed by TAK-994 placebo-matching tablets, orally, on Days 1 and 2 of Treatment Period 2, further followed by TAK-994 Dose B tablets, orally, on Days 1 and 2 of Treatment Period 3. A Washout Period of at least 7 days will be maintained between each treatment period.	Drug: TAK-994; TAK-994 tablets.; Drug: Placebo; TAK-994 placebo-matching tablets.
Experimental: TAK-994 Dose B + TAK-994 Dose A + Placebo; TAK-994 Dose B tablets, orally, on Days 1 and 2 of Treatment Period 1, followed by TAK-994 Dose A tablets, orally, on Days 1 and 2 of Treatment Period 2, further followed by TAK-994 placebo-matching tablets, orally, on Days 1 and 2 of Treatment Period 3. A Washout Period of at least 7 days will be maintained between each treatment period.	Drug: TAK-994; TAK-994 tablets.; Drug: Placebo; TAK-994 placebo-matching tablets.
Experimental: Placebo + TAK-994 Dose B+ TAK-994 Dose A; TAK-994 placebo-matching tablets, orally, on Days 1 and 2 of Treatment Period 1, followed by TAK-994 Dose B tablets orally, on Days 1 and 2 of Treatment Period 2, further followed by TAK-994 Dose A tablets, orally, on Days 1 and 2 of Treatment Period 3. A Washout Period of at least 7 days will be maintained between each treatment period.	Drug: TAK-994; TAK-994 tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants who Experience at Least 1 Treatment Emergent Adverse Event (TEAE) During the Study		From first dose of the study drug up to Day 7 after the last dose of study drug on Day 2 in Treatment Period 3 (up to Day 27)
Number of Participants who Meet the Markedly Abnormal Value for Safety Laboratory Tests at Least Once Postdose During the Study		From first dose of the study drug up to Day 7 after the last dose of study drug on Day 2 in Treatment Period 3 (up to Day 27)
Number of Participants who Meet the Markedly Abnormal Value for Vital Sign Measurements at Least Once Postdose During the Study		From first dose of the study drug up to Day 7 after the last dose of study drug on Day 2 in Treatment Period 3 (up to Day 27)
Number of Participants who Meet the Markedly Abnormal Value for Safety Electrocardiogram (ECG) Parameters at Least Once Postdose During the Study		From first dose of the study drug up to Day 7 after the last dose of study drug on Day 2 in Treatment Period 3 (up to Day 27)
Mean Sleep Latency Over Four Maintenance of Wakefulness Test (MWT) Sessions After Initial Dosing	MWT is a validated objective measure that evaluates a person's ability to remain awake under soporific conditions for a defined period of time. Tendency to fall asleep is measured via electroencephalography-derived sleep latency. Mean sleep latency: mean time to sleep onset, over 4 MWT sessions (at approximately 2, 4, 6, and 8 hours after initial dosing).	Up to 8 hours after initial dosing in each treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax: Maximum Observed Plasma Concentration for TAK-994		Days 1 and 2: Pre-dose and at multiple time points (up to 10 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-994		Days 1 and 2: Pre-dose and at multiple time points (up to 10 hours) post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-994		Days 1 and 2: Pre-dose and at multiple time points (up to 10 hours) post-dose
Change From Baseline in Mean Karolinska Sleepiness Scale (KSS) Score	The KSS is a 10-item, Likert-type rating scale for assessing subjective sleepiness. This participant self-rating scale measures the subjective level of sleepiness at the time of administration.	Baseline up to 8.75 hours after initial dosing in each treatment period

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2020
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: September 11, 2020
• First Submitted That Met QC Criteria: September 15, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 14, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy
• Other Study ID Numbers: TAK-994-1503; U1111-1256-7132 (Registry Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No