Acute manic episodes associated with Bipolar I Disorder MedDRA version: 20.0 Level: PT Classification code 10004939 Term: Bipolar I disorder System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Product Name: Iloperidone
Product Code: VYV-683
Pharmaceutical Form: Capsule
INN or Proposed INN: ILOPERIDONE
CAS Number: 133454-47-4
Current Sponsor code: VYV-683
Concentration unit: mg milligram(s)
Sponsors
Vanda Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each patient must meet the following criteria for inclusion in the study: 1. Patients must provide written informed consent (IC) before any assessment is performed. Additionally, if a patient is not mentally stable to provide consent their legal guardian must also sign the inform consent form in accordance with the regulatory requirements for their respective country. 2. Males or non-fecund females (i.e., surgically sterilized, if procedure was done 6 months before screening or patient is postmenopausal, without menses for 12 months before screening), or females of childbearing potential using adequate contraception from 1 month prior to randomization through 1 month after the last dose of study medication. Note: Examples of acceptable methods of contraception for females include the use of 2 independent barrier methods, hormonal contraception plus 1 barrier method, or surgically sterilized partner. 3. Patients must be 18 through 65 years of age inclusive. 4. Patients with Body Mass Index (BMI) of >18 and =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1 Patients with a DSM-5 diagnosis of a psychiatric disorder other than bipolar I disorder that was the primary focus of treatment within the previous 6 m. 2 Patients with diagnosis or history suggestive of chemical dependence according to DSM-5 criteria, or toxic psychosis in the preceding 6 m., or a clinical presentation possibly confounded by the use of recreational drugs or alcohol 3 Patients experiencing a first manic episode or meeting criteria for rapid cycling 4 Patients who are mentally disabled (moderate to severe) and cannot understand the IC or participate fully in the assessments. 5 Patients with a significant brain trauma or a coma lasting more than 24 h. 6 Patients who are currently at imminent risk of harm to self or others 7 Patients with a positive urine drug screen (at the screening visit) for amphetamines, cocaine, PCP, benzodiazepines, or barbiturates will be excluded. If opiates are positive at screening, patients must provide sufficient evidence that they have been prescribed these medications and are taking them as prescribed. Patients must also be clinically evaluated for dependency and excluded if there is sufficient suspicion. If benzodiazepine is positive at screening, patients may be allowed to continue if the use is PRN. If benzodiazepine use is chronic, patients will still need to be excluded 8 Patients known to suffer from blindness, deafness, language difficulties, or any other sensory or motor deficits that may prevent the patient from completing any of the study requirements 9 Patients who have suffered from significant physical illness in the 4w period preceding baseline will be excluded, unless the Investigator provides a rationale for including a specific patient and has approval of the Medical Monitor 10 Patients who suffer from other clinically significant medical conditions which could be expected to progress, recur, or change to such an extent that they may put the patient at special risk or bias the assessment of the clinical and the mental status of the patient to a significant degree will be excluded. This includes any nonpsychiatric coexistent disease state that has not been maintained in a stable condition for at least 3 m prior to baseline 11 Patient with known congenital long QT syndrome, Brugada syndrome, or other cardiac abnormality that would increase the risk of ventricular arrhythmia. 12 Patients who suffer from any clinically significant disease of the gastrointestinal system, liver, or kidneys, or any abnormal condition that compromises the function of these systems and could result in the possibility of altered absorption, excess accumulation, or impairment of metabolism or excretion of the study medication 13 Patients that have a clinically significant abnormal laboratory finding, which remained abnormal upon being repeated ONCE and that suggests a medical condition that would put the patient at special risk or significantly bias assessment of the patient’s clinical status 14 Patients that have one or more of the following serological results: a Current hepatitis C infection b A positive hepatitis B surface antigen (HbsAg) c Elevated (> or = 1.5 times the upper lime of normal) LFTs (SGOT, SGPT, LDH, alkaline phosphate, or bilirubin) and one of the following: positive hepatitis A (HAV IgM) or positive hepatitis B core antibody (HBcAb-IgM) 15 Patients with a current diagnosis or past history of epilepsy, major head trauma, or progressive neurological disease (other than tar
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Study Primary Objective: • To evaluate the efficacy of iloperidone monotherapy compared to placebo in the treatment of adult patients with bipolar I disorder experiencing an acute manic or mixed episode as measured by reduction in the Young Mania Rating Scale (YMRS) total score at Week 4 Primary Objective for the Optional Long-Term Open-Label Phase: • To explore the long-term safety and tolerability of dosing with iloperidone over an additional 52 weeks of treatment ;Secondary Objective: •Evaluate efficacy of iloperidone monotherapy vs placebo in the treatment of adult patients diagnosed with bipolar I disorder experiencing an acute manic or mixed episode as measured by: 1) improvements in the CGI-S 2) reduction in the YMRS total score at each trial visit 3) improvement in clinical symptoms in the CGI-C 4) improvement in clinical symptoms in the MADRS •Assess the rate of YMRS responders. A YMRS responder is defined as at least a 50% decrease from baseline in YMRS total score •Assess safety & tolerability of iloperidone vs placebo in the treatment of adult patients in an acute manic or mixed episode of bipolar I disorder as measured by changes in vital signs and weight, laboratory analytes, ECGs, and the incidence and severity of TEAEs and extrapyramidal symptoms using the BARS, SAS, and the AIMS Exploratory objective: conduct a whole genome association scan to identify potential markers of response and safety for a bipolar indication;Primary end point(s): The primary efficacy outcome measure is the change from baseline in the Young Mania Rating Scale (YMRS);Timepoint(s) of evaluation of this end point: YMRS total score at Week 4. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Mean baseline-to-endpoint change in total score using following parameters: Efficacy parameters: • Young Mania Rating Scale (YMRS) • Overall and mania severity of illness for Clinical Global Impression of Severity (CGI-S) • Clinical Global Impression of Change (CGI-C) • Montgomery-Asberg Depression Rating Scale (MADRS) Safety parameters: • Adverse Events (AEs) and proportion of patients withdrawing due to AEs • EPS scale scores as measured by Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), and Barnes Akathisia Rating Scale (BARS) • Metabolic risk factors, clinical chemistry, hematology, vital signs, and weight • Columbia Suicide-Severity Rating Scale (C-SSRS) • CYP2D6 genotyping • 12-lead electrocardiograms (ECG) ;Timepoint(s) of evaluation of this end point: Efficacy parameters: • YMRS is completed at visits 1 to 8, 11, 14, 15 and 16 • CGI-C is completed at visits 3 to 8, 11, 14, 15 and 16 • CGI-S is completed at visits 2 to 8, 11, 14, 15 and 16 • MADRS is completed at visits 2, 3, 5, 6, 7, 8, 11, 14, 15 and 16 Safety parameters: • SAS, BARS and AIMS are completed at visits 1 to 8, 11, 14, 15 and 16 • C-SSRS is completed in all visits • CYP2D6 genotyping is performed at screening (visit 1) Safety will be monitored throughout the entire study and as described in study protocol. | — |
Countries
Bulgaria, Poland, Russian Federation, Ukraine, United States
Contacts
Public ContactClinical trial information
Vanda Pharmaceuticals Inc.
Outcome results
None listed