Effects of TAK-063 on Preventing Ketamine-Induced Brain Activity Changes as Well as Psychotic-Like Symptoms in Healthy Male Adults

NCT ID: NCT01892189

Last Updated: 2017-01-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-08-31

Study Completion Date

2014-08-31

Brief Summary

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The purpose of this study is to determine whether ketamine-induced brain activity changes are modulated by TAK-063 administration using neuroimaging battery tests.

Detailed Description

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The drug being tested in this study is called TAK-063. This study will look at brain activity changes and treatment of psychotic-like symptoms induced by ketamine, in people who take TAK-063.

The study will enroll approximately 27 participants. Participants will be randomly assigned to one of treatment sequences-which will remain undisclosed to the participants during the study (unless there is an urgent medical need). Participants will receive the following study medications by the end of the study:

* Ketamine intravenous infusion (IV) AND
* Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient AND
* Two doses of TAK-063 at one of three dose levels All participants will be asked to take 3 tablets and will receive a ketamine IV on the first day of 3 separate study periods. Participants will then be assessed for brain activity changes and other symptoms. This single-center trial will be conducted in the United States. The overall time to participate in this study is up to 7 weeks. Participants will make 6 visits to the clinic.

Conditions

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Ketamine-Induced Brain Activity Changes Psychotic-like Symptoms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Sequence 1: Placebo + TAK-063 3 mg + TAK-063 30 mg

Period 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 3 milligram (mg), orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight.

Period 1 \& 2 are followed by 7 day washout period.

Group Type EXPERIMENTAL

Ketamine

Intervention Type DRUG

Ketamine intravenous administration.

TAK-063

Intervention Type DRUG

TAK-063 tablets

TAK-063 Placebo

Intervention Type DRUG

TAK-063 placebo-matching tablets

Sequence 2: TAK-063 3 mg + TAK-063 30 mg + Placebo

Period 1, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight.

Period 1 \& 2 are followed by 7 day washout period.

Group Type EXPERIMENTAL

Ketamine

Intervention Type DRUG

Ketamine intravenous administration.

TAK-063

Intervention Type DRUG

TAK-063 tablets

TAK-063 Placebo

Intervention Type DRUG

TAK-063 placebo-matching tablets

Sequence 3: TAK-063 30 mg + Placebo + TAK-063 3 mg

Period 1, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight.

Period 1 \& 2 are followed by 7 day washout period.

Group Type EXPERIMENTAL

Ketamine

Intervention Type DRUG

Ketamine intravenous administration.

TAK-063

Intervention Type DRUG

TAK-063 tablets

TAK-063 Placebo

Intervention Type DRUG

TAK-063 placebo-matching tablets

Sequence 4: Placebo + TAK-063 3 mg + TAK-063 300 mg

Period 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight.

Period 1 \& 2 are followed by 7 day washout period.

Group Type EXPERIMENTAL

Ketamine

Intervention Type DRUG

Ketamine intravenous administration.

TAK-063

Intervention Type DRUG

TAK-063 tablets

TAK-063 Placebo

Intervention Type DRUG

TAK-063 placebo-matching tablets

Sequence 5: TAK-063 3 mg + TAK-063 300 mg+ Placebo

Period 1, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight.

Period 1 \& 2 are followed by 7 day washout period

Group Type EXPERIMENTAL

Ketamine

Intervention Type DRUG

Ketamine intravenous administration.

TAK-063

Intervention Type DRUG

TAK-063 tablets

TAK-063 Placebo

Intervention Type DRUG

TAK-063 placebo-matching tablets

Sequence 6: TAK-063 300 mg + Placebo + TAK-063 3 mg

Period 1, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight.

Period 1 \& 2 are followed by 7 day washout period.

Group Type EXPERIMENTAL

Ketamine

Intervention Type DRUG

Ketamine intravenous administration.

TAK-063

Intervention Type DRUG

TAK-063 tablets

TAK-063 Placebo

Intervention Type DRUG

TAK-063 placebo-matching tablets

Sequence 7: Placebo + TAK-063 30 mg + TAK-063 300 mg

Period 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight:

Period 2, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight.

Period 1 \& 2 are followed by 7 day washout period

Group Type EXPERIMENTAL

Ketamine

Intervention Type DRUG

Ketamine intravenous administration.

TAK-063

Intervention Type DRUG

TAK-063 tablets

TAK-063 Placebo

Intervention Type DRUG

TAK-063 placebo-matching tablets

Sequence 8: TAK-063 30 mg + TAK-063 300 mg + Placebo

Period 1, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight.

Period 1 \& 2 are followed by 7 day washout period.

Group Type EXPERIMENTAL

Ketamine

Intervention Type DRUG

Ketamine intravenous administration.

TAK-063

Intervention Type DRUG

TAK-063 tablets

TAK-063 Placebo

Intervention Type DRUG

TAK-063 placebo-matching tablets

Sequence 9: TAK-063 300 mg + Placebo + TAK-063 30 mg

Period 1, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period

Group Type EXPERIMENTAL

Ketamine

Intervention Type DRUG

Ketamine intravenous administration.

TAK-063

Intervention Type DRUG

TAK-063 tablets

TAK-063 Placebo

Intervention Type DRUG

TAK-063 placebo-matching tablets

Interventions

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Ketamine

Ketamine intravenous administration.

Intervention Type DRUG

TAK-063

TAK-063 tablets

Intervention Type DRUG

TAK-063 Placebo

TAK-063 placebo-matching tablets

Intervention Type DRUG

Other Intervention Names

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Ketalarâ„¢

Eligibility Criteria

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Inclusion Criteria

1. In the opinion of the investigator, participant is capable of understanding and complying with protocol requirements.
2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Is a healthy adult male.
4. Speaks English as their first language.
5. Is aged 18 to 45 years, inclusive, at the time of informed consent and first dose of study drug.
6. Weighs at least 50 kg and has a body mass index (BMI) between 18 and 32 kilogram per metre square (kg/m\^2), inclusive at Screening.
7. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.
8. Has a normal magnetic resonance imaging (MRI) scan and electroencephalogram (EEG) measurement at Screening.

Exclusion Criteria

1. Has received any investigational compound or ketamine within 30 days prior to Day 1 of Period 1.
2. Has received TAK-063 in a previous clinical study or as a therapeutic agent.
3. Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
4. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality (including MRI or EEG), which may impact the ability of the participant to participate or potentially confound the study results.
5. Has a known hypersensitivity to any component of the formulation of TAK-063 or ketamine.
6. Has a contraindication for ketamine.
7. Has a positive result for drugs or alcohol at Screening or Check-in (Day -1 of Period 1).
8. Has a history of drug or alcohol abuse or dependence (as defined by Diagnostic \& Statistical Manual of Mental Disorders, fourth Edition \[DSM-IV\]) within 1 year prior to the screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
9. Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products.
10. Has evidence of current cardiovascular, central nervous system (CNS), hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-063 or ketamine or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
11. Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis frequent \[more than once per week\] occurrence of heartburn, or any surgical intervention \[e.g., cholecystectomy\]).
12. Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1 of Period 1.
13. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), or a known history of human immunodeficiency virus infection at Screening.
14. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in (Day -1 of Period 1) or cotinine test is positive at Screening or Check-in (Day -1 of Period 1).
15. Has poor peripheral arterial/venous access or recent wrist trauma.
16. Has donated or lost 450 mL or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 3 months prior to Day 1 of Period 1.
17. Has a Screening and/or Check-in (Day -1 of Period 1) abnormal (clinically significant) electrocardiogram (ECG). Participant has a supine blood pressure outside the ranges of 90 to 140 mm Hg for systolic and 50 to 90 mm Hg for diastolic, if out of range may be repeated once for eligibility determination at the Screening Visit or Check-in (Day -1 of Period 1).
18. Has a resting heart rate outside the range 50 to 90 beats per minute (bpm), if out of range may be repeated once for eligibility determination at the Screening Visit and/or Check-in (Day -1 of Period 1).
19. Has a QT interval with Fridericia correction method (QTcF) greater than (\>) 430 milliseconds (ms) or PR outside the range 120 to 220 ms, if out of range may be repeated once for eligibility determination within a maximum of 5 minutes, at the Screening Visit and/or Check-in (Day -1 of Period 1).
20. Has abnormal Screening laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>1.5 upper limit of normal (ULN).
21. Has a history of Axis I/II mental disorders according to DSM-IV Axis I/II such as depression, anxiety disorders, bipolar disorder, attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders, anorexia nervosa, bulimia nervosa, and schizophrenia.
22. Has a history of head injury or trauma.
23. Has any condition that would prevent an MRI from accurately or safely being performed (e.g., claustrophobia, cardiac pacemaker, metallic implants or clips), as verified per study site's standard MRI assessment questionnaire.
24. Has a risk of suicide according to the Investigator's clinical judgment (e.g., per Columbia-Suicide Severity Rating Scale \[C-SSRS\]) or has made a suicide attempt in the previous 6 months prior to Screening.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Takeda

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Takeda Development Center Americas, Inc.

Locations

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The Brain Institute, University of Utah

Salt Lake City, Utah, United States

Site Status

Countries

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United States

Other Identifiers

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U1111-1141-2177

Identifier Type: OTHER

Identifier Source: secondary_id

TAK-063_102

Identifier Type: -

Identifier Source: org_study_id

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