Clinical trial NCT04551079: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2020-09-16
Enrollment: 19
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Number of Participants who Experience at Least 1 Treatment Emergent Adverse Event (TEAE) During the Study
timeFrame: 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)
measure: Number of Participants who Meet the Markedly Abnormal Value for Safety Laboratory Tests at Least Once Postdose During the Study
timeFrame: 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)
measure: Number of Participants who Meet the Markedly Abnormal Value for Vital Sign Measurements at Least Once Postdose During the Study
timeFrame: 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)
measure: Number of Participants who Meet the Markedly Abnormal Value for Safety Electrocardiogram (ECG) Parameters at Least Once Postdose During the Study
timeFrame: 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)
measure: Mean Sleep Latency Over Four Maintenance of Wakefulness Test (MWT) Sessions After Initial Dosing
timeFrame: Up to 8 hours after initial dosing in each treatment period
Secondary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for TAK-994
timeFrame: Days 1 and 2: Pre-dose and at multiple time points (up to 10 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-994
timeFrame: Days 1 and 2: Pre-dose and at multiple time points (up to 10 hours) post-dose
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-994
timeFrame: Days 1 and 2: Pre-dose and at multiple time points (up to 10 hours) post-dose
measure: Change From Baseline in Mean Karolinska Sleepiness Scale (KSS) Score
timeFrame: Baseline up to 8.75 hours after initial dosing in each treatment period
Other outcomes:
Locations:
city: New York
country: United States
facility: Clinilabs Drug Development Corporation
state: New York
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: