Clinical trial NCT03522506: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of TAK-925 Study in Sleep-Deprived Healthy Adults
Official title: A Phase 1b, 4-Period Crossover, Placebo-Controlled, Randomized, Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-925 in Sleep-Deprived Healthy Adults Utilizing Modafinil as an Active Comparator
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-05-11
Enrollment: 20
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 determine the effect of TAK-925 after a single intravenous dose (compared to placebo) on promoting wakefulness as measured by sleep latency on the maintenance of wakefulness (MWT) in sleep-deprived healthy participants.

Detailed description: The drug being tested in this study is called TAK-925. This study will assess the safety, tolerability, PK and PD of TAK-925 and will assess the effects of TAK-925 in sleep-deprived healthy adult participants.

The study will enroll approximately 20 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the 4 treatment sequences-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

* TAK-925 Low Dose + Placebo + TAK-925 High Dose + Modafinil
* TAK-925 High Dose + TAK-925 Low Dose + Modafinil + Placebo
* Modafinil+ TAK-925 High Dose + Placebo + TAK-925 Low Dose
* Placebo + Modafinil + TAK-925 Low Dose + TAK-925 High Dose

TAK-925 will be administered as an intravenous infusion based on the availability of safety, tolerability and PK data from health Japanese participants in ongoing study TAK-925-1001.

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 make a final visit 7 days after receiving their last dose of drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Has a positive alcohol or drug screen.
2. Has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to: beer \[354 milliliter per (mL/)12 ounces\], wine (118 mL/4 ounces), or distilled spirits (29.5 mL/1 ounce)\] per day).
3. Has excessive sleepiness defined by a self-reported Epworth Sleepiness Scale score at screening greater than 10; irregular work hours; or routine night-shift work within 1 month before randomization.
4. Currently experiencing or having a history of any known/suspected sleep disorder, any disorder associated with excessive daytime somnolence (EDS), or any diagnosis interfering with assessment of sleepiness.
5. Abnormal findings on the initial polysomnography (PSG) conducted on Day -1 (check-in), as specified in the study manual.
6. Traveled across 2 or more time zones 2 weeks or less before screening.
7. Caffeine consumption of more than 400 milligram per day (mg/day) for 2 weeks before screening (1 serving of coffee is approximately equivalent to 120 mg of caffeine).

Primary outcomes:
measure: Latency to Sleep Onset on Maintenance of Wakefulness Test (MWT) at 2 Hours Post-infusion Start
timeFrame: Day 1: 2 hours post-infusion start
measure: Latency to Sleep Onset on MWT at 4 Hours Post-infusion Start
timeFrame: Day 1: 4 hours post-infusion start
measure: Latency to Sleep Onset on MWT at 6 Hours Post-infusion Start
timeFrame: Day 1: 6 hours post-infusion start
measure: Latency to Sleep Onset on MWT at 8 Hours Post-infusion Start
timeFrame: Day 1: 8 hours post-infusion start
measure: Latency to Sleep Onset on MWT at 1 Hour Post-end of Infusion
timeFrame: Day 1: 1 hour post-end of infusion
Secondary outcomes:
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M-I and M-II
timeFrame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M-I and M-II
timeFrame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
measure: Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M-I and M-II
timeFrame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
measure: Ceoi: Plasma Concentration Observed at the End of Infusion for TAK-925 and Its Metabolites M-I and M-II
timeFrame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M-I and M-II
timeFrame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
measure: T1/2z: Terminal Disposition Phase Half-life for TAK-925 and Its Metabolites M-I and M-II
timeFrame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
measure: CL: Total Clearance After Intravenous Administration for TAK-925
timeFrame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
measure: Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-925
timeFrame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
measure: Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925
timeFrame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
measure: Sleepiness on KSS
timeFrame: Day 1: 14, 10, 6, 2 hours pre-infusion; 2.75, 4.75, 6.75. 8.75 hours post-infusion start; 1.75 hours post-infusion end
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: PRA Health Sciences
state: Utah
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: