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

NCT02614586 | Terminated Phase 1 Results

• 2 other identifiers: TAK-058-1003U1111-1168-1522
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in P50 Ratio S2/S1 at Central (Cz) Electrode Following Administration of TAK-058

  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.

  Part 2: Day 1 pre-dose and at multiple time points (up to 2 hours) post-dose in each period.

Secondary Outcomes (1)

• Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)

  Part 2: Day 1 of Intervention Period 1 up to Day 21

Study Arms (6)

Placebo + TAK-058 + Ondansetron

EXPERIMENTAL

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; Drug: Ondansetron; Drug: TAK-058 Placebo; Drug: Ondansetron Placebo

TAK-058 + Placebo + Ondansetron

EXPERIMENTAL

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; Drug: Ondansetron; Drug: TAK-058 Placebo; Drug: Ondansetron Placebo

Ondansetron + Placebo + TAK-058

EXPERIMENTAL

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; Drug: Ondansetron; Drug: TAK-058 Placebo; Drug: Ondansetron Placebo

Placebo + Ondansetron + TAK-058

EXPERIMENTAL

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; Drug: Ondansetron; Drug: TAK-058 Placebo; Drug: Ondansetron Placebo

TAK-058 + Ondansetron + Placebo

EXPERIMENTAL

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; Drug: Ondansetron; Drug: TAK-058 Placebo; Drug: Ondansetron Placebo

Ondansetron + TAK-058 + Placebo

EXPERIMENTAL

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; Drug: Ondansetron; Drug: TAK-058 Placebo; Drug: Ondansetron Placebo

Interventions

TAK-058 DRUG

TAK-058 oral solution.

Ondansetron + Placebo + TAK-058; Ondansetron + TAK-058 + Placebo; Placebo + Ondansetron + TAK-058; Placebo + TAK-058 + Ondansetron; TAK-058 + Ondansetron + Placebo; TAK-058 + Placebo + Ondansetron

Ondansetron DRUG

Ondansetron capsule.

Ondansetron + Placebo + TAK-058; Ondansetron + TAK-058 + Placebo; Placebo + Ondansetron + TAK-058; Placebo + TAK-058 + Ondansetron; TAK-058 + Ondansetron + Placebo; TAK-058 + Placebo + Ondansetron

TAK-058 Placebo DRUG

TAK-058 placebo-matching, solution.

Ondansetron + Placebo + TAK-058; Ondansetron + TAK-058 + Placebo; Placebo + Ondansetron + TAK-058; Placebo + TAK-058 + Ondansetron; TAK-058 + Ondansetron + Placebo; TAK-058 + Placebo + Ondansetron

Ondansetron Placebo DRUG

Ondansetron placebo-matching, capsule.

Ondansetron + Placebo + TAK-058; Ondansetron + TAK-058 + Placebo; Placebo + Ondansetron + TAK-058; Placebo + TAK-058 + Ondansetron; TAK-058 + Ondansetron + Placebo; TAK-058 + Placebo + Ondansetron

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• to 60 years of healthy and schizophrenic participants, inclusive, at the time of informed consent.
• Has acceptable clinical laboratory evaluations (including clinical chemistry, hematology and complete urinalysis).
• Meets schizophrenia criteria as defined by the Diagnostic \& Statistical Manual of Mental Disorders, 5th Edition (DSM-V).
• 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.
• Demonstrates Positive and Negative Syndrome Scale (PANSS) total score of less than equal to (\<=) 85.
• Has a P50 ratio of \> 0.5 at both screening assessments.

You may not qualify if:

• Has a history in the last year or currently receiving treatment with clozapine or olanzapine.
• Has taken any excluded medications, supplements or food products.
• 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.
• Has substance abuse or dependence within previous 12 months, unstable mood or anxiety disorder.
• Has a current diagnosis of a significant psychiatric illness other than schizophrenia per DSM-V and is in an acute phase/episode.
• Has clinically meaningful hearing loss per investigator's judgment.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

St Louis, Missouri, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Ondansetron

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2015
• First Posted: November 25, 2015
• Study Start: December 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: May 1, 2017
• Results First Posted: May 1, 2017

Record last verified: 2017-03

Locations

US (1)