Phase 1 N=24 Randomized Double-blind Other

A Study to Evaluate Central Nervous System (CNS) Pharmacodynamic Activity of TAK-653 in Healthy Participants Using Transcranial Magnetic Stimulation (TMS)

Healthy Volunteers

Bottom Line

View on ClinicalTrials.gov: NCT03792672 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jul 2020

Primary outcome: Primary: Change From Baseline in Peak-to-Peak Amplitude of Motor-evoked Potential (MEP) Obtained With Single-pulse Transcranial Magnetic Stimulation (TMS) for TAK-653 at 2.5 Hours Post TAK-653 Dose — 898.828; 841.068; 1004.127; -139.117 microvolt (mcV) — p=0.4278

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: TAK-653 (Drug); Placebo (Drug); Ketamine (Drug)
Age: Adult · 18+ yrs
Sex: All
Sponsor: Neurocrine Biosciences
Primary completion: May 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Peak-to-Peak Amplitude of Motor-evoked Potential (MEP) Obtained With Single-pulse Transcranial Magnetic Stimulation (TMS) for TAK-653 at 2.5 Hours Post TAK-653 Dose	898.828; 841.068; 1004.127; -139.117; 17.265; 139.932	0.4278
PRIMARY Change From Baseline in Resting Motor Threshold (rMT) Obtained With Single-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose	55.3; 55.9; 55.3; -0.1; -0.5; -0.3	0.5089
SECONDARY Change From Baseline in Magnitude of Long Intracortical Inhibition (LICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose	75.113; 96.515; 96.568; 0.675; 18.319; 19.395	0.4174
SECONDARY Change From Baseline in Magnitude of Short Intracortical Inhibition (SICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose	43.095; 39.159; 47.951; 5.052; 1.772; -14.580	0.5590
SECONDARY Change From Baseline in rMT Obtained With Single-pulse TMS to Assess the Effect of Ketamine at 2.5 Hours and 24 Hours Post-dose of Ketamine	54.4; 0.7; 0.8	—
SECONDARY Change From Baseline in in Peak-to-Peak Amplitude of MEP Obtained With Single-pulse TMS to Assess the Effect of Ketamine at 2.5 Hours and 24 Hours Post Dose of Ketamine	1150.618; -193.897; -295.041	—

Summary

The primary purpose of this study is to determine whether TAK-653, in comparison to placebo, increases CNS excitability, assessed with TMS-evoked motor-evoked potential (MEP) in healthy participants.

Eligibility Criteria

Inclusion Criteria

Must be judged to be in good health by the investigator, based on clinical evaluations including laboratory safety tests, medical history, physical examination, 12-lead electrocardiogram (ECG), and vital sign measurements performed at the screening visit and before the first dose of study drug.
Must be male or female (of nonchildbearing potential) aged 18 to 55 years, inclusive, at the screening visit.
Must have a body mass index (BMI) greater than or equal to (>=) 18.5 and less than or equal to (<=) 30.0 kilogram per square meter (kg/m^2) at the screening visit.

Exclusion Criteria

Has a positive alcohol or drug screen.
Had major surgery or donated or lost 1 unit of blood (approximately 500 milliliter [mL]) within 4 weeks before the screening visit.
Has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to the following: beer [354 mL/12 ounce (oz)], wine [118 mL/4 oz], or distilled spirits [29.5 mL/1 oz] per day).
Who regularly smoke more than 5 cigarettes daily or equivalent and unable or unwilling not to smoke during the in-house period.
Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.
Has a previous or current clinically significant psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5) including substance use disorder.
Has a history of intracranial mass lesion, hydrocephalus and/or head injury or trauma.
Has metal objects in brain or skull.
Has a cochlear implant or deep brain stimulation device.
Has a history of epilepsy, seizures, or convulsions.
Has a family history of epilepsy, seizures, or convulsions.
Has abnormal sleeping patterns (example, working night shifts)
Has an rMT of more than 75% of the maximum stimulator output, measured using TMS-electromyogram (EMG) during screening.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03792672). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.