Tolerability and Pharmacokinetics of Iloperidone in Adolescent Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01495169
First received: August 31, 2011
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

Tolerability, undertstanding of the action of the drug in the body, and understanding the effect of the drug in adolescent patients needing treatment with an antipsychotic medication


Condition Intervention Phase
Safety and Tolerability of Iloperidone
Drug: iloperidone (oral tablet)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Sequential Cohort, Dose-escalation, 14-day Study to Explore the Tolerability and Pharmacokinetics of Iloperidone 12 to 24 mg/Day Followed by 26 Weeks of Flexible Dosing (6 to 24 mg/Day) in Adolescent Patients (Aged 12 to 17 Years)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Pharmacokinetics of iloperidone at different dose levels based on AUC (area under the plasma concentration time curve during a dosage interval) Cmax ss (maximum plasma concentration at steady state), Tmax ss (time to Cmax at steady state). [ Time Frame: Visit 5, 6, 7 (after at least 7 days of iloperidone treatment at the same dose level) ] [ Designated as safety issue: No ]
    Pharmacokinetics describes the action of a drug in the body over a period of time. Blood samples are collected to measure plasma concentrations of the study drug at different times after dosing. From the plasma concentration data, AUC, Cmax ss, and Tmax ss are calculated.

  • Tolerability of iloperidone at different dose levels [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    Frequency of treatment emergent adverse events, frequency of clinically notable changes from baseline in vital signs, electrocardiograms, laboratory tests, and reponses on movement disorder rating scales (Barnes Akathisia Rating Scale, Simpson-Angus Scale) and on a rating scale for suicidal thoughts and behaviors (Columbia Suicide Severity Rating Scale)


Secondary Outcome Measures:
  • Number of Patients with Adverse Events, Serious Adverse Events or Death [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
    Safety and tolerability profile in open-label extension

  • Change from baseline in Clinical Global Impression of Improvement Scale (CGI-I) [ Time Frame: Baseline, then Weekly for 2 weeks, then every 2-4 weeks for 26 weeks ] [ Designated as safety issue: No ]
    The CGI-I is scored from 1 to 7 and assesses the overall degree of illness relative to baseline. A CGI-I rating of 4 is equivalent to "no change." Ratings less than 4 are equivalent to "improvement" and ratings of more than 4 are equivalent to "worsening."

  • Change from baseline in the Children's Global Asessment Scale (CGAS [ Time Frame: Baseline, then Weekly for 2 weeks, then every 2-4 weeks for 26 weeks ] [ Designated as safety issue: No ]
    The CGAS) is a numeric scale (1 through 100) used to rate the general functioning of children; high scores indicate better functioning.

  • Effect of iloperidone on QT, QT beat-to-beat (QTbtb), QT corrected using the Fridericia formulat (QTcF), QT corrected using the Bazett formula (QTcB), individual based correct QT (QTcI) [ Time Frame: Baseline (24 hours), Visit 3 (4-hours post initial dose), and Visit 7 (13 hours ] [ Designated as safety issue: Yes ]
    Patients wear a holter monitor for ~24 hours during the baseline period, for an additional 4 hours after the first dose, and for ~13 hours after they have been on the same dose for at least 7 days to compare how the heart beats before and after the study drug is taken. The holter monitor transmits continuous data to a computer on how the heart beats for the time when the monitor is on and is a better measurement than data collected by a traditional electrocardiogram (ECG), which provides data on a limited number of heart beats over a short period of time.

  • Clinically notable changes from baseline on electrocardiogram (ECG) parameters (QTcF, QTcB, QRS, PR, heart rate) [ Time Frame: Screening, baseline, 5x over 2 weeks, then every 2-4 weeks for 26 weeks ] [ Designated as safety issue: Yes ]
    Three ECGs are obtained for each assessment. The values are averaged for each ECG parameter (QTcF, QTcB, QRS, PR interval, heart rateare) and clinically notable changes from baseline and new or worsening heart rhythm disorders are identified


Estimated Enrollment: 29
Study Start Date: October 2011
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Iloperidone
Part A (dose-escalation and fixed dose): Eligible patients receive iloperidone 2mg/day (1 mg BID) on day 1, then escalated every day for up to 12days utilizing a forced titration regimen to achieve a maximum dose of 12, 16, 20 or 24 mg/day given BID. Part B (optional extension phase): Patients who successfully complete Part A of the study are eligible to continue treatment with iloperidone for an additional 26 weeks
Drug: iloperidone (oral tablet)
iloperidone 12 to 24 mg/day followed by 26 weeks of flexible dosing (6 to 24 mg/day)

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • males or females 12-17 years of age.
  • in a stable housing situation with a guardian/parent who can encourage compliance with the study protocol.
  • with diagnosis of disorder requiring treatment with an antipsychotic agent.
  • having a Children's Global Assessment of Severity Scale (CGAS) of 41 or greater.
  • Heart rate </=100 beats per minute and >/= 50 beats per minute.

Exclusion Criteria:

  • Patients with mild, moderate or severe mental retardation (i.e., documented IQ <70), do not have the capacity to assent, cannot understand the informed consent, or participate fully in the assessments.
  • Hospitalized due to suicidal ideation or suicidal behavior, history of suicidal ideation within 6 months prior to screening, history of suicidal behavior within 2 years prior to screening.
  • Pregnant, females who can become pregnant and lactating females.
  • Known hypersensitivity to iloperidone and to related drugs.
  • Clinical conditions (Neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal or urological), which may pose significant risk to patients or impair reliable study participation.
  • Clinically unstable cardiac disease, structural cardiac abnormalities, congential long QT syndrome, clinically significant ECG abnormalities at screening (PR interval >240 ms, QTcF >450 ms, QRS duration >/= 100 ms) or arrhythmias.
  • Syncope, near syncope, or palpitations. Other protocol-defined inclusion/exclusion criteria may apply.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01495169

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, Arkansas
Novartis Investigative Site Withdrawn
Little Rock, Arkansas, United States, 72211
United States, California
Novartis Investigative Site Not yet recruiting
Costa Mesa, California, United States, 92626
Novartis Investigative Site Withdrawn
Oceanside, California, United States, 92056
Novartis Investigative Site Withdrawn
San Diego, California, United States, 92123
United States, Florida
Novartis Investigative Site Not yet recruiting
North Miami, Florida, United States, 33161
United States, Georgia
Novartis Investigative Site Not yet recruiting
Atlanta, Georgia, United States, 30308
United States, Idaho
Novartis Investigative Site Not yet recruiting
Coeur d'Alene, Idaho, United States, 83814
United States, Maryland
Novartis Investigative Site Not yet recruiting
Baltimore, Maryland, United States, 21205
United States, Minnesota
Novartis Investigative Site Withdrawn
Minneapolis, Minnesota, United States, 55454
United States, Missouri
Novartis Investigative Site Recruiting
St. Louis, Missouri, United States, 63044
United States, Nebraska
Novartis Investigative Site Withdrawn
Lincoln, Nebraska, United States, 68510
United States, Nevada
Novartis Investigative Site Withdrawn
Las Vegas, Nevada, United States, 89128
United States, New Jersey
Novartis Investigative Site Not yet recruiting
Marlton, New Jersey, United States, 08053
United States, Ohio
Novartis Investigative Site Recruiting
Cincinnati, Ohio, United States, 45219
Novartis Investigative Site Not yet recruiting
Cleveland, Ohio, United States, 44106-5000
Novartis Investigative Site Withdrawn
Columbus, Ohio, United States, OH 43210
United States, Texas
Novartis Investigative Site Withdrawn
Houston, Texas, United States, 77008
Novartis Investigative Site Withdrawn
Lake Jackson, Texas, United States, 77566
United States, Utah
Novartis Investigative Site Withdrawn
Murray, Utah, United States, 84107
Novartis Investigative Site Not yet recruiting
Salt Lake City, Utah, United States, 84106
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01495169     History of Changes
Other Study ID Numbers: CILO522D2402
Study First Received: August 31, 2011
Last Updated: June 5, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Novartis:
Antipsychotic
Schizophrenia
Bipolar disorder
Iloperidone

ClinicalTrials.gov processed this record on October 30, 2014