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

• ClinicalTrials.gov Identifier: NCT02614586
• Recruitment Status: Terminated
• First Posted: November 25, 2015
• Results First Posted: May 1, 2017
• Last Update Posted: May 1, 2017
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Drug: TAK-058; Drug: Ondansetron; Drug: TAK-058 Placebo; Drug: Ondansetron Placebo	Phase 1

Detailed 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 approximately 118 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• 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
• Study Start Date: December 2015
• Actual Primary Completion Date: April 2016
• Actual Study Completion Date: April 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Placebo + TAK-058 + Ondansetron; TAK-058 placebo-matching solution, orally, along with ondansetron placebo-matching capsule, orally, on Day 1 of first intervention period (2 days), followed by 1 week washout period, further followed by TAK-058 150 milligram (mg), solution, orally along with ondansetron placebo-matching capsule orally, on Day 1 of second intervention period (2 days), followed by 1 week washout period, further followed by ondansetron 16 mg, capsule, orally along with TAK-058 placebo-matching solution, orally, on Day 1 of third intervention period (2 days).	Drug: TAK-058; TAK-058 oral solution.; Drug: Ondansetron; Ondansetron capsule.; Drug: TAK-058 Placebo; TAK-058 placebo-matching, solution.; Drug: Ondansetron Placebo; Ondansetron placebo-matching, capsule.
Experimental: TAK-058 + Placebo + Ondansetron; TAK-058 150 mg, solution, orally along with ondansetron placebo-matching capsule orally, on Day 1 of first intervention period (2 days), followed by 1 week washout period, further followed by TAK-058 placebo-matching solution, orally, along with ondansetron placebo-matching capsule, orally, on Day 1 of second intervention period (2 days), followed by 1 week washout period, further followed by ondansetron 16 mg, capsule, orally, along with TAK-058 placebo-matching solution, orally, on Day 1 of third intervention period (2 days).	Drug: TAK-058; TAK-058 oral solution.; Drug: Ondansetron; Ondansetron capsule.; Drug: TAK-058 Placebo; TAK-058 placebo-matching, solution.; Drug: Ondansetron Placebo; Ondansetron placebo-matching, capsule.
Experimental: Ondansetron + Placebo + TAK-058; Ondansetron 16 mg, capsule, orally, along with TAK-058 placebo-matching solution, orally, on Day 1 of first intervention period (2 days), followed by 1 week washout period, further followed by TAK-058 placebo-matching solution, orally, along with ondansetron placebo-matching capsule, orally, on Day 1 of second intervention period (2 days), followed by 1 week washout period, further followed by TAK-058 150 mg, solution, orally, along with ondansetron placebo-matching capsule, orally, on Day 1 of third intervention period (2 days).	Drug: TAK-058; TAK-058 oral solution.; Drug: Ondansetron; Ondansetron capsule.; Drug: TAK-058 Placebo; TAK-058 placebo-matching, solution.; Drug: Ondansetron Placebo; Ondansetron placebo-matching, capsule.
Experimental: Placebo + Ondansetron + TAK-058; TAK-058 placebo-matching solution, orally, along with ondansetron placebo-matching capsule, orally, on Day 1 of first intervention period (2 days), followed by 1 week washout period, further followed by ondansetron 16 mg, capsule, orally, along with TAK-058 placebo-matching solution, orally, on Day 1 of second intervention period (2 days), followed by 1 week washout period, further followed by TAK-058 150 mg, solution, orally, along with ondansetron placebo-matching capsule, orally, on Day 1 of third intervention period (2 days).	Drug: TAK-058; TAK-058 oral solution.; Drug: Ondansetron; Ondansetron capsule.; Drug: TAK-058 Placebo; TAK-058 placebo-matching, solution.; Drug: Ondansetron Placebo; Ondansetron placebo-matching, capsule.
Experimental: TAK-058 + Ondansetron + Placebo; TAK-058 150 mg, solution, orally along with ondansetron placebo-matching capsule orally, on Day 1 of first intervention period (2 days), followed by 1 week washout period, further followed by ondansetron 16 mg, capsule, orally, along with TAK-058 placebo-matching solution, orally, on Day 1 of second intervention period (2 days), followed by 1 week washout period, further followed by TAK-058 placebo-matching solution, orally, along with ondansetron placebo-matching capsule, orally, on Day 1 of third intervention period (2 days).	Drug: TAK-058; TAK-058 oral solution.; Drug: Ondansetron; Ondansetron capsule.; Drug: TAK-058 Placebo; TAK-058 placebo-matching, solution.; Drug: Ondansetron Placebo; Ondansetron placebo-matching, capsule.
Experimental: Ondansetron + TAK-058 + Placebo; Ondansetron 16 mg, capsule, orally along with TAK-058 placebo-matching solution, orally, on Day 1 of first intervention period (2 days), followed by 1 week washout period, further followed by TAK-058 150 mg, solution, orally, along with ondansetron placebo-matching capsule, orally, on Day 1 of second intervention period (2 days), followed by 1 week washout period, further followed by TAK-058 placebo-matching solution, orally, along with ondansetron placebo-matching capsule, orally, on Day 1 of third intervention period (2 days).	Drug: TAK-058; TAK-058 oral solution.; Drug: Ondansetron; Ondansetron capsule.; Drug: TAK-058 Placebo; TAK-058 placebo-matching, solution.; Drug: Ondansetron Placebo; Ondansetron placebo-matching, capsule.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in P50 Ratio S2/S1 at Central (Cz) Electrode Following Administration of TAK-058 [ Time Frame: Part 2: Day 1 pre-dose and at multiple time points (up to 2 hours) post-dose in each period. ]
   Participants were planned to check for P50 gating ratio. Stimulus signal of 90 decibel pulses of 0.1 millisecond (msec) was to be generated and recorded the event-related potential waveforms. 32 pairs of auditory clicks were to be presented every 10 seconds, with a 500 msec interclick interval. S1 is defined as the conditioning P50 wave with the most positive peak between 30 and 90 msec 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) was to be collected and the P50 gating ratio (S2/S1) was to be calculated as the ratio of the test P50 amplitude to the conditioning P50 amplitude.

Secondary Outcome Measures :

1. Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) [ Time Frame: Part 2: Day 1 of Intervention Period 1 up to Day 21 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Missouri

St. Louis, Missouri, United States

Sponsors and Collaborators

Takeda

Investigators

• Study Director: Medical Director; Takeda

More Information

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02614586
• Other Study ID Numbers: TAK-058-1003; U1111-1168-1522 ( Registry Identifier: WHO )
• First Posted: November 25, 2015
• Results First Posted: May 1, 2017
• Last Update Posted: May 1, 2017
• Last Verified: March 2017

Keywords provided by Takeda:

Drug Therapy

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Ondansetron; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipruritics; Dermatologic Agents; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Anti-Anxiety Agents