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

NCT ID: NCT03792672

Last Updated: 2021-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-11
• Study Completion Date: 2019-06-18

Brief 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.

Detailed Description

The drug being tested in this study is called TAK-653. This study is designed to evaluate the central pharmacodynamic activity of TAK-653 using TMS. The study will enroll approximately 24 participants to yield 22 participants that complete treatment periods 1, 2, and 3. Participants will be randomly assigned to 1 of the 6 sequences to receive TAK-653 0.5 mg low dose or TAK-653 6 mg high dose or Placebo in double-blind treatment periods 1, 2, and 3, followed by Ketamine 0.5 mg/kg in open-label Treatment period 4.

All participants will receive one dose of TAK-653 (0.5 or 6 mg), or Placebo or Ketamine on Day 1 of each treatment period.

This single center trial will be conducted in the Netherlands. The overall time to participate in this study is 15 weeks. Participants will make 5 visits to the clinic. A washout period of minimum 10 days will be maintained between the doses in treatment periods 1 to 3. Follow-up phone call will be made on Day 14.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

TAK-653 6 mg + TAK-653 0.5 mg + Placebo + Ketamine 0.5 mg/kg

TAK-653 6 milligram (mg) high dose tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 milligram per kilogram (mg/kg), intravenous infusion, once on Day 1 of Treatment Period 4. A washout of 10 to 15 days will be maintained between each treatment period.

Group Type: EXPERIMENTAL

TAK-653

Intervention Type: DRUG

TAK-653 tablets.

Placebo

Intervention Type: DRUG

TAK-653 placebo-matching tablets.

Ketamine

Intervention Type: DRUG

Ketamine intravenous infusion.

TAK-653 6 mg + Placebo + TAK-653 0.5 mg + Ketamine 0.5 mg/kg

TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, intravenous infusion, once on Day 1 of Treatment Period 4. A washout of 10 to 15 days will be maintained between each treatment period.

Group Type: EXPERIMENTAL

TAK-653

Intervention Type: DRUG

TAK-653 tablets.

Placebo

Intervention Type: DRUG

TAK-653 placebo-matching tablets.

Ketamine

Intervention Type: DRUG

Ketamine intravenous infusion.

TAK-653 0.5 mg + TAK-653 6 mg + Placebo + Ketamine 0.5 mg/kg

TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, intravenous infusion, once on Day 1 of Treatment Period 4. A washout of 10 to 15 days will be maintained between each treatment period.

Group Type: EXPERIMENTAL

TAK-653

Intervention Type: DRUG

TAK-653 tablets.

Placebo

Intervention Type: DRUG

TAK-653 placebo-matching tablets.

Ketamine

Intervention Type: DRUG

Ketamine intravenous infusion.

TAK-653 0.5 mg + Placebo + TAK-653 6 mg + Ketamine 0.5 mg/kg

TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, intravenous infusion, once on Day 1 of Treatment Period 4. A washout of 10 to 15 days will be maintained between each treatment period.

Group Type: EXPERIMENTAL

TAK-653

Intervention Type: DRUG

TAK-653 tablets.

Placebo

Intervention Type: DRUG

TAK-653 placebo-matching tablets.

Ketamine

Intervention Type: DRUG

Ketamine intravenous infusion.

Placebo + TAK-653 0.5 mg + TAK-653 6 mg + Ketamine 0.5 mg/kg

TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, intravenous infusion, once on Day 1 of Treatment Period 4. A washout of 10 to 15 days will be maintained between each treatment period.

Group Type: EXPERIMENTAL

TAK-653

Intervention Type: DRUG

TAK-653 tablets.

Placebo

Intervention Type: DRUG

TAK-653 placebo-matching tablets.

Ketamine

Intervention Type: DRUG

Ketamine intravenous infusion.

Placebo + TAK-653 6 mg + TAK-653 0.5 mg + Ketamine 0.5 mg/kg

TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, intravenous infusion, once on Day 1 of Treatment Period 4. A washout of 10 to 15 days will be maintained between each treatment period.

Group Type: EXPERIMENTAL

TAK-653

Intervention Type: DRUG

TAK-653 tablets.

Placebo

Intervention Type: DRUG

TAK-653 placebo-matching tablets.

Ketamine

Intervention Type: DRUG

Ketamine intravenous infusion.

Interventions

TAK-653

TAK-653 tablets.

Intervention Type: DRUG

Placebo

TAK-653 placebo-matching tablets.

Intervention Type: DRUG

Ketamine

Ketamine intravenous infusion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Must be male or female (of nonchildbearing potential) aged 18 to 55 years, inclusive, at the screening visit.

3. 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

1. Has a positive alcohol or drug screen.

2. Had major surgery or donated or lost 1 unit of blood (approximately 500 milliliter [mL]) within 4 weeks before the screening visit.

3. 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).

4. Who regularly smoke more than 5 cigarettes daily or equivalent and unable or unwilling not to smoke during the in-house period.

5. 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.

6. 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.

7. Has a history of intracranial mass lesion, hydrocephalus and/or head injury or trauma.

8. Has metal objects in brain or skull.

9. Has a cochlear implant or deep brain stimulation device.

10. Has a history of epilepsy, seizures, or convulsions.

11. Has a family history of epilepsy, seizures, or convulsions.

12. Has abnormal sleeping patterns (example, working night shifts)

13. Has an rMT of more than 75% of the maximum stimulator output, measured using TMS-electromyogram (EMG) during screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Takeda

INDUSTRY

Sponsor Role: collaborator

Neurocrine Biosciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

CHDR

Leiden, , Netherlands

Countries

Netherlands

References

Dijkstra F, O'Donnell P, Klaassen E, Buhl D, Asgharnejad M, Rosen L, Zuiker R, van Gerven J, Jacobs G. Central nervous system effects of TAK-653, an investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole receptor (AMPAR) positive allosteric modulator in healthy volunteers. Transl Psychiatry. 2022 Sep 24;12(1):408. doi: 10.1038/s41398-022-02148-w.

Reference Type: DERIVED

PMID: 36153330 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1224-5430

Identifier Type: OTHER

Identifier Source: secondary_id

2018-004206-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL68394.056.18

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-653-1003

Identifier Type: -

Identifier Source: org_study_id