Evaluation of TAK-058 and Ondansetron on P50 Auditory Gating in Participants With Stable Schizophrenia

Schizophrenia Clinical Trial

Official title:

A Placebo-Controlled Study to Evaluate the Effect of a Single Dose of TAK-058 and Ondansetron on P50 Auditory Gating in Subjects With Stable Schizophrenia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02614586
• Other study ID #: TAK-058-1003
• Secondary ID: U1111-1168-1522
• Status: Terminated
• Phase: Phase 1
• First received: November 23, 2015
• Last updated: October 24, 2016
• Start date: December 2015
• Est. completion date: June 2016

Study information

• Verified date: October 2016
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether improvement in P50 (a pharmacodynamic marker) in auditory sensory gating is demonstrated after administration of TAK-058 and ondansetron compared to placebo in participants with schizophrenia.

Description:

The drug being tested in this study is called TAK-058. TAK-058 is being tested to evaluate its effects on P50 auditory gating in people who have stable schizophrenia. This study will look at the effect of TAK-058 on P50 auditory gaiting of people with schizophrenia.

This study will be performed in a sequential manner progressing from an optimization (screening) phase in healthy volunteers, to screening of subjects with schizophrenia in part 1, to a 3 period crossover treatment phase in part 2. In the screening phase, 15 healthy volunteers will be enrolled to optimize the settings for the measurement of neurophysiological markers prior to any dosing in participants with schizophrenia. If optimization is not reached, the study will be terminated. In part 1 participants with schizophrenia will receive 2 P50 electroencephalography (EEG) sessions. A measurable deficit in auditory P50 gating S2/S1 ratio greater than (>) 0.5 will be established during this phase. The intraclass correlation coefficient (ICC) will be calculated for the P50 auditory gating S2/S1 ratios collected during the 2 sessions. If these P50 auditory gating S2/S1 ratio measurements are found to have at least a fair level of agreement within individuals (that is, ICC > 0.5), part 2 of the study will begin. 12 participants demonstrating P50 impairment in part 1, will be randomly assigned (by chance, like flipping a coin) to one of the six treatment crossover sequences —which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

• Placebo + TAK-058 + Ondansetron

• TAK-058 + Placebo + Ondansetron

• Ondansetron + Placebo + TAK-058

• Placebo + Ondansetron + TAK-058

• TAK-058 + Ondansetron + Placebo

• Ondansetron + TAK-058 + Placebo

All participants will be asked to take one dose of capsule, followed 1 hour later by one dose of solution on Day 1 of each intervention period.

This single-center trial will be conducted in the United States. The overall time to participate in this study is approximately118 days. Participants will make be confined to the clinic for 3 days (Day -1 through Day 2 of each period), a final visit for schizophrenic participants in Part 2 after receiving TAK-058, on Day 2 of Period 3 (no final visit for optimization phase healthy participants), and a telephonic follow up assessment 21 days after last dose of study drug.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 45
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. 18 to 60 years of healthy and schizophrenic participants, inclusive, at the time of informed consent.

2. Has acceptable clinical laboratory evaluations (including clinical chemistry, hematology and complete urinalysis).

3. Meets schizophrenia criteria as defined by the Diagnostic & Statistical Manual of Mental Disorders, 5th Edition (DSM-V).

4. Are on a stable dose of single second-generation antipsychotics (SGA) for at least 2 months prior to Screening as documented by medical history and assessed by site staff.

5. Demonstrates Positive and Negative Syndrome Scale (PANSS) total score of less than equal to (<=) 85.

6. Has a P50 ratio of > 0.5 at both screening assessments.

Exclusion Criteria:

1. Has a history in the last year or currently receiving treatment with clozapine or olanzapine.

2. Has taken any excluded medications, supplements or food products.

3. Has a history of gastrointestinal disease that would influence the absorption of study drug or have a significant medical history of any disease that would contraindicate the administration of TAK-058, ondansetron, or a similar compound.

4. Has substance abuse or dependence within previous 12 months, unstable mood or anxiety disorder.

5. Has a current diagnosis of a significant psychiatric illness other than schizophrenia per DSM-V and is in an acute phase/episode.

6. Has clinically meaningful hearing loss per investigator's judgment.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• TAK-058
TAK-058 oral solution.
• Ondansetron
Ondansetron capsule.
• TAK-058 Placebo
TAK-058 placebo-matching, solution.
• Ondansetron Placebo
Ondansetron placebo-matching, capsule.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in P50 Ratio (Stimulus [S]2/S1) at Central (Cz) Electrode Following Administration of TAK-058	Participants will be checked for P50 gating ratio. Stimulus signal of 90 decibel pulses of 0.1 millisecond (msec) will be generated and recorded the event-related potential waveforms. 32 pairs of auditory clicks will be presented every 10 seconds, with a 500 ms interclick interval. S1 is defined as the conditioning P50 wave with the most positive peak between 30 and 90 ms after the conditioning stimulus. S2 is defined as the test P50 wave with the positive peak after the test stimulus that was closest in latency to the conditioning P50. Amplitude is the difference between the positive peak and the preceding negative trough for both waves. The data from the vertex (Cz site) is to be collected and the P50 gating ratio (S2/S1) is calculated as the ratio of the test P50 amplitude to the conditioning P50 amplitude.	Day 1 pre-dose and at multiple time points (up to 2 hours) in each period of Part 2 post-dose	No
Secondary	Percentage of Participants who Experience at Least one Treatment Emergent Adverse Event (TEAE)	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.	Day 1 of Period 1 of Part 2, up to 21 days after last dose of study drug in Part 2	Yes