CTRI/2022/06/043537 [Registered on: 28/06/2022] Trial Registered Prospectively
Last Modified On:
08/08/2024
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Other
Public Title of Study
An Open-Label, Randomized, Two-Way Crossover, Multiple Dose, Comparative Bioavailability study of Aripiprazole ER IS (400 mg) in patients with schizophrenia.
Scientific Title of Study
A Randomized, Open-Label, Two-Way Crossover, Multiple-Dose, Comparative Bioavailability Study of Aripiprazole Extended-Release Injectable Suspension (400 mg) (Apotex Inc.) Versus Abilify Maintena® (Aripiprazole) Extended-Release Injectable Suspension (400 mg) (Otsuka America Pharmaceutical, Inc.) (USA) in Patients with Schizophrenia.
Saraswati Mandir Complex Near Bhutnath Temple, College Road Junagadh GUJARAT
2852653652
bakulbuch@gmail.com
Dr Sabari Sridhar OT
Sri Ramachandra Institute of Higher Education and Research (SRIHER)
Clinical Research Facility, Dental College Basement, Sri Ramachandra Institute of Higher Education and Research (SRIHER)
No.: 1, Ramachandra Nagar, Porur, Chennai TAMIL NADU
9443557921
psychiatryclinicaltrials@gmail.com
Dr Shivanand B Hiremath
Sushruta Multispeciality Hospital and Research Centre
Each patient will be randomly assigned in 1:1 ratio to receive a test or reference product of Aripiprazole Extended-Release Injectable Suspension 400mg for intramuscular use via single deltoid IM injections at monthly (i.e., 28±2 days) intervals for consecutive six doses (i.e. on Day-0, Day-28, Day-56, Day-84, Day-112, Day-140) as per randomization schedule. Patients will then be switched over to the other formulation for the next consecutive six doses (i.e. on Day-168, Day-196, Day-224, Day-252, Day-280 and Day-308).
Each patient will be randomly assigned in 1:1 ratio to receive a test or reference product of Aripiprazole Extended-Release Injectable Suspension 400mg for intramuscular use via single deltoid IM injections at monthly (i.e., 28±2 days) intervals for consecutive six doses (i.e. on Day-0, Day-28, Day-56, Day-84, Day-112, Day-140) as per randomization schedule. Patients will then be switched over to the other formulation for the next consecutive six doses (i.e. on Day-168, Day-196, Day-224, Day-252, Day-280 and Day-308).
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Males and females 18-65 years of age.
2. Patient and legally acceptable representative (LAR: e.g. family member) willing and able to provide written Informed Consent and comply with the requirements of the study.
3. Diagnosed with schizophrenia, as defined in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), in a non-acute (e.g., chronic) phase and clinically stable in the judgment of the Investigator for at least 8 weeks before Screening.
4. At time of Screening be on a stable regimen of aripiprazole ER injection (400 mg) for at least 8 weeks before Screening or aripiprazole oral 10 mg- 20 mg daily for at least 8 weeks before Screening.
5. General health status acceptable per judgment of the Investigator for participation in this clinical study with no hospitalizations for medical conditions within 12 weeks before and during Screening. Any question regarding general health status eligibility will be addressed with the Medical Monitor.
6. Female patients with childbearing potential must have a negative serum pregnancy test at Screening and at Baseline (Day -1), or must be postmenopausal (amenorrhea for at least 2 years and follicle-stimulating hormone [FSH] > 40 mIU/mL), or surgically sterile (for one year), or practicing or agree to practice an effective method of birth control if they are sexually active before study entry, during the study and 3 months after the end of the study by using an acceptable method of contraception. Acceptable methods of birth control must be used for at least 30 days prior to the use of study drug. Acceptable methods of birth control include abstinence, oral, vaginal or patch contraceptive, copper intrauterine device, or double-barrier method (e.g., condom, diaphragm or cervical cap with spermicidal foam, cream, gel or suppository).
7. Body mass index of 18.0-38.0 kg/m2 inclusive.
8. No clinically significant abnormal laboratory values.
9. No clinically significant findings in the 12-lead electrocardiogram (ECG).
10. No clinically significant findings from a vital sign measurement.
11. Patients must have an identified support person as LAR considered reliable by the Investigator to help ensure compliance with study treatment and visits and to alert staff of any issues of concern.
12. Patients must have a stable place of residence for the 3 months prior to Screening.
13. Patients must not have been either hospitalized for worsening of schizophrenic symptoms or judged by the Investigator as having significant exacerbation of schizophrenic symptoms during the 3 months prior to Screening.
ExclusionCriteria
Details
1. Patients with a primary and active DSM-5 diagnosis other than schizophrenia.
2. Patients currently on aripiprazole lauroxil (Aristada).
3. Have a known hypersensitivity to aripiprazole or to any excipients in the formulation.
4. Patients who pose a significant risk of a suicide attempt based on history or the Investigator’s judgment, or who answer “yes†to Suicidal Ideation items 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) for current or past 30 days on the “Baseline/Screening version†at Screening or “Since Last Visit version†at Baseline, or who have suicidal behavior in the last 12 months as measured by the C-SSRS at Screening or Baseline; or are at imminent risk of suicide or violent behavior based on the Investigator’s clinical assessment or the C-SSRS assessment of lifetime suicidal ideation or behavior at screening.
5. Patients with a history of neuroleptic malignant syndrome or tardive dyskinesia, or a history of severe akathisia or severe extra-pyramidal reactions such as dystonia with previous use of aripiprazole or other neuroleptic treatments, or a score of 4 or above on the Global Clinical Assessment of the Barnes Akathisia Rating Scale (BARS) at Screening.
6. Patients with uncontrolled diabetes mellitus, or a HbA1c level ≥ 7%, or with diabetes mellitus requiring use of insulin. Patients with newly diagnosed Type 2 diabetes during the screening period are excluded, however stable (30 days or longer) Type 2 diabetes will be allowed.
7. Patients with a history of or who are currently diagnosed as having epilepsy or convulsion disorders.
8. Patients who are CYP2D6 poor metabolizers.
9. Patients who used medication known to be a potent or moderate inhibitor of CYP 2D6, or potent inhibitor of CYP 3A4 or a potent inducer of CYP 3A4 within 30 days or 5 PK half-lives for the specific medication, whichever is longer, prior to Screening or between Screening and Baseline visit (Day -1). Patients who used monoamine oxidase (MAO) Inhibitors 30 days prior to screening or between screening and baseline visit (Day -1).
10. Patients who regularly consume grapefruit or Seville oranges.
11. Patients meeting DSM-5 criteria for moderate or severe alcohol or substance use disorder (other than nicotine- or caffeine-related disorders) within 6 months of Screening or test positive for a drug of abuse or alcohol at Screening or Baseline (except positive findings that can be accounted for by documented prescription use prescribed by a treating clinician as a part of the treatment for the patient’s acute medical condition (i.e., tooth extraction).
12. Patients with a history of, or current clinically relevant cardiac arrhythmia, cardiovascular disease, thyrotoxicosis, parkinsonism, or hemorrhagic diathesis.
13. Patients who have a history of malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
14. Female patients who are pregnant or tested positive for pregnancy at Screening or Baseline, or are breastfeeding, or are of childbearing potential without adequate use of contraception.
15. Patients who have any uncontrolled, unstable clinically relevant medical condition (e.g. hepatic, renal, cardiovascular, endocrine, respiratory, hematologic, immunologic or cerebrovascular disease), or other medical condition, which in the judgment of the Investigator would interfere with the patients ability to participate in the study.
16. Patients with a QT interval corrected using Fridericia formula (QTcF) interval >450 ms for males and > 470 ms for females, or other clinically significant ECG findings in the opinion of the Investigator.
17. Positive serology for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) Type 1 or 2 antibodies.
18. Patients who have donated blood (> 500 mL) or blood products within 2 months (56 days) prior to the Baseline visit (Day -1).
19. Patients who have received an investigational drug as part of a clinical study within 30 days prior to screening or current participation in another clinical study with an investigational drug or planned participation in another clinical study with an investigational drug concurrent with the duration of this clinical study.
20. Excessive smoking, defined as smoking more than 2 packs of cigarettes (or 5 cigars) per day for ≥ 1 year or intention to significantly change the smoking habits during the study (i.e. planned cessation or start of smoking career).
21. Patients who show any clinical observation, clinical laboratory abnormality, or abnormal ECG findings at Screening or Baseline visit (Day -1), which in the opinion of the Investigator may endanger the patient or interfere with the endpoints of study. If the results of clinical laboratory or ECG testing are outside normal reference ranges, the patient may be enrolled only if these findings are determined to be not clinically significant by the Investigator. This determination must be recorded in the patient’s source document.
22. Patients who are unable to understand the protocol requirements, instructions and study related restrictions, the nature, scope and possible consequences of the clinical study.
23. Patients who are unlikely to comply with the protocol requirements, instructions and study-related restrictions (e.g., uncooperative attitude, inability to return for all scheduled monthly injections per the schedule or the outpatient visits or improbability of completing the clinical study).
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
To assess the comparative bioavailability of aripiprazole ER IS (400 mg) (Test) to Abilify Maintena® (aripiprazole) ER IS (400 mg) (Reference).
EOS Day 336
Secondary Outcome
Outcome
TimePoints
To assess the safety and tolerability of aripiprazole - Test in comparison to Abilify Maintena - Reference by evaluating the nature, severity, and frequency of their AE profiles and local skin reactions.
Time-Point
Approximately 48 weeks of Study duration
Target Sample Size
Total Sample Size="58" Sample Size from India="58" Final Enrollment numbers achieved (Total)= "58" Final Enrollment numbers achieved (India)="58"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study is designed as an open-label,
randomized, two-way crossover design, multiple-dose study to evaluate the
bioequivalence of a Long Acting Injectable (LAI) anti-psychotic, aripiprazole ER
IS (400 mg) compared to Abilify Maintena® ER IS (400 mg) in
schizophrenic patients already stabilized on Aripiprazole.