CTRI/2024/08/072829 [Registered on: 21/08/2024] Trial Registered Prospectively
Last Modified On:
10/03/2026
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Other
Public Title of Study
Bioequivalence Study of Aripiprazole 400 mg Powder and Solvent for Prolonged-Release Suspension for Injection .
Scientific Title of Study
An Open-Label, Randomized, Two-Treatment, Two-Period, Two-Sequence, Multiple-Dose, Steady-State, Fully Replicate, Crossover Bioequivalence Study of Aripiprazole 400 mg Powder and Solvent for Prolonged-Release Suspension for Injection and Abilify Maintena® 400 mg Powder and Solvent for Prolonged-Release Suspension for Injection in Adult Patients with
Schizophrenia under Fasting Condition.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
2023-ARIP0260-PK-03 Version: 02 Date: 13 Mar 24
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Dharmesh Domadia
Designation
Vice President - Global Clinical Operations
Affiliation
Cliantha Research Limited
Address
Cliantha Research Limited,
Cliantha Corporate,
TP 86, FP 28/1,
Off S.P. Ring Road, Sarkhej,
Ahmedabad-382210,
Gujarat, India
Ahmadabad GUJARAT 382210 India
Phone
07966219555
Fax
Email
ddomadia@cliantha.com
Details of Contact Person Scientific Query
Name
Dr Ankesh Barnwal
Designation
Associate Director - II
Affiliation
Cliantha Research Limited
Address
Cliantha Research Limited,
Cliantha Corporate,
TP 86, FP 28/1,
Off S.P. Ring Road, Sarkhej,
Ahmedabad-382210,
Gujarat, India
Ahmadabad GUJARAT 382210 India
Phone
07966219545
Fax
Email
abarnwal@cliantha.com
Details of Contact Person Public Query
Name
Mr Devesh Verma
Designation
Director
Affiliation
Cliantha Research Limited
Address
Cliantha Research Limited,
Cliantha Corporate,
TP 86, FP 28/1,
Off S.P. Ring Road, Sarkhej,
Ahmedabad-382210,
Gujarat, India
Dose - 400 mg
frequency - six doses
ROA – Injection
Total duration 4 Week
Intervention
Aripiprazole 400 mg Powder and Solvent for Prolonged - Release Suspension for Injection
Dose - 400 mg
frequency - six doses
ROA – Injection
Total duration 4 Week
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male or non-pregnant, non-lactating female patient between 18 and 65 years of age (both inclusive).
2. Patient with documented diagnosis of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders – 5th edition (DSM-V) criteria.
3. Patient with Body Mass Index (BMI) ≥18 to less than 30 kg/m2 and weight not less than 50 kg.
4. Patient who is clinically stable and have had no hospitalization for exacerbation of psychiatric symptoms during the 3 months before screening and till randomization.
5. Patient is clinically stable on aripiprazole 10-20 mg for the past 3 months who require chronic antipsychotic treatment and who will benefit from initiating treatment with aripiprazole 400 mg powder and solvent for prolonged-release suspension for injection.
6. Patient and LAR must demonstrate adequate decision-making ability to make an informed decision about participating in this study by providing written informed consent.
7. Patient who agrees to comply with the visit schedule and other requirements of the study.
ExclusionCriteria
Details
1. Patient with known or suspected allergy or hypersensitivity to aripiprazole or other constituents of the formulation.
2. Patient having signs and symptoms suggestive of COVID-19 (such as fever, dry cough, difficulty in breathing, fatigue etc.)
3. History of medically significant adverse events or intolerance with aripiprazole based on investigators discretion.
4. Patient on drugs known to be inducer or inhibitor of CYP3A4 and CYP2D6 enzymes (allowed if on a stable regimen of at least 1 month based on Principal Investigators discretion)
Note:
a. If the patient was on any of these drugs, sufficient wash out period (of at least 5 half-lives) must have elapsed since the last dose of such drug and the first dose of study medication.
b. Individuals with co-administered weak CYP3A4 and CYP2D6 inhibitors will be allowed if on a stable regimen of at least 1 month based on Principal Investigator’s discretion in consultation with medical monitor and with plans to remain on that stable regimen throughout the course of this study.
5. Patient who is poor metabolizer of CYP2D6 enzyme.
6. Patient with Clinical Global Impression – Severity of illness (CGIS) score of 5 or more.
7. Patient with inadequate muscle mass to receive the intramuscular injection according to the investigator.
8. Patient with a history of Neuroleptic Malignant Syndrome (NMS) or tardive dyskinesia while on treatment with atypical antipsychotics.
9. Patient with dementia related psychosis.
10. History or presence of pathological gambling and other compulsive behaviors.
11. Patient with history or presence of seizures or other conditions that potentially lower the seizure threshold.
12. Presence of significant orthostatic hypotension (i.e., decrease in systolic blood pressure ≥20 mmHg or diastolic BP of ≥10 mmHg when comparing standing to supine values) or uncontrolled hypertension (systolic BP ≥150 mmHg/diastolic BP ≥ 100 mmHg).
13. Patient with known cardiovascular disease (example, heart failure, history of myocardial infarction or ischemia), cerebrovascular disease, or conditions that predispose the patient to hypotension (example, dehydration, hypovolemia, and treatment with antihypertensive medications), uncontrolled metabolic disorders including uncontrolled hyperglycemia/diabetes mellitus (HbA1c ≥ 9 %) or Dyslipidemia.
14. Patient with a history of a corrected QT interval greater than 450 msec (Bazett’s formula)
15. History of drug induced leukopenia/neutropenia/agranulocytosis.
16. Patient with abnormal haematological parameters at screening and randomization defined by:
a. Total white blood cell count less than 4000/mm3.
b. ANC less than 1500/mm3.
c. Platelet count less than 100,000/mm3.
d. Haemoglobin less than 9.0 gm/dl.
17. Patient with abnormal liver function tests at screening and randomization as defined by:
a. Bilirubin greater than 1.5 x ULN.
b. AST and ALT greater than 5 x ULN.
18. History of alcohol or substance abuse in the immediate 6-month period prior to screening.
19. Patient who smokes or chews tobacco products.
20. Any changes in antipsychotic medication or dosage during the past 3 months prior to the randomization.
21. Received Electroconvulsive Therapy (ECT) within the last 3 months prior to screening.
22. Patient with suicidal ideation (score of 4 or 5 on the Columbia Suicide Severity Rating Scale [C-SSRS]) within the past 2 months or any suicidal behavior occurring in the past year.
23. Patient who had major surgery within 4 weeks prior to study entry, who have not recovered from prior major surgery, or who have surgery scheduled during the course of the study.
24. Patient with known positivity for human immunodeficiency virus (HIV), HBsAg and/or HCV, Syphilis (RPR/VDRL).
25. Patient with history or at risk of venous thromboembolism as per investigator’s discretion.
26. Patient having any other clinically significant finding of the physical examination or laboratory value or any reason which, in the opinion of the investigator, would prevent the patient from safely participating in the study.
27. Male or female of childbearing potential unwilling to use adequate methods of contraception throughout the study.
28. History of difficulty with donating blood or difficulty in accessibility of veins.
29. Donation of blood (1 unit or 350 mL) within 90 days prior to receiving the first dose of investigational medicinal product in the study.
30. Participation in any interventional clinical study within the past 90 days of randomization.
31. Institutionalized patient.
Method of Generating Random Sequence
Other
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
To demonstrate the bioequivalence
End of Study: Week 49 (Day 337)
Secondary Outcome
Outcome
TimePoints
To evaluate the safety and tolerability
End of Study: Week 49 (Day 337)
Target Sample Size
Total Sample Size="72" Sample Size from India="72" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
N/A
Date of First Enrollment (India)
02/12/2024
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="2" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Closed to Recruitment of Participants
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is an
Open-Label, Randomized, Two-Treatment, Two-Period, Two-Sequence, Multiple-Dose,
Steady-State, Fully Replicate, Crossover Bioequivalence Study of Aripiprazole
400 mg Powder and Solvent for Prolonged-Release
Suspension for Injection and Abilify Maintena® 400
mg Powder and Solvent for Prolonged-Release Suspension for Injection in Adult
Patients with Schizophrenia under Fasting Condition.
The
study includes a screening period, a tolerability test period, a treatment
period and end of study visit. All patients will undergo stabilisation period.
Visit Schedules:
Screening period:Screening safety assessments
will be performed within 21 days prior to the initiation of stabilisation
period.
Stabilisation period: Eligible
patient on a stable regimen of oral aripiprazole 10-20 mg who require chronic
antipsychotic treatment and who will benefit from initiating treatment with monthly
regimen of marketed aripiprazole 400 mg powder and solvent for
prolonged-release suspension for injection based on the judgment of the
treating physician or Investigator, will switch from their oral aripiprazole
dose regimen to a monthly regimen of aripiprazole 400 mg powder and solvent for
prolonged-release suspension for injection until 3 consecutive monthly doses
have been administered.
Treatment Period: During
the treatment period, each patient will be randomised in a ratio of 1:1 to
either of two sequences (Test product (T) to Reference product (R), or
Reference product (R) to Test product (T) and receive six consecutive doses of
400 mg Test product (T) or 400 mg Reference product (R) of Aripiprazole
Prolonged Release Injectable Suspension 400 mg/vial (2.0 mL) at predefined
injection site into the gluteal (buttock) muscle region by deep intramuscular
route 28 days apart in a crossover design during two periods (Period I and
Period II).
Dosing
andAdministration: Each
patient will be randomly assigned to receive test or reference product of
Aripiprazole powder and solvent for Prolonged-Release Suspension for Injection
400 mg/vial (2.0 mL), at predefined injection site in the gluteal (buttock)
region by deep intramuscular route, 28 days apart for consecutive six dosing’s(i.e.
on Day-1, Day-29, Day-57, Day-85, Day-113, Day-141 in Period I) as per
randomization schedule. Patients will then be switched over to the other
treatment arm for the next consecutive six doses (i.e. on Day-169, Day-197, Day-225,
Day-253, Day-281 and Day-309 in Period II).
Housing
Details:
During
the stabilisation period all patients will need to remain in the study centre
on the day of injection for at least 2 hours before dosing and at least 2 hours
after dosing.
During
the treatment period, all patients will be housed in the study centre as
mentioned below:
Period
Dose
Check-In
Check-Out
I
1
to 4
2
hours before
dosing
4
hours after
dosing
II
5
and 6
10
hours before
dosing
24
hours after
dosing
I
7
to 10
2
hours before
dosing
4
hours after
dosing
II
11
and 12
10
hours before
dosing
24
hours after
dosing
Collection
of Blood samples:
All
blood samples (3.0 mL each) will be collected in labelled K2EDTA-vacutainers.
A
total of 86 blood samples per each patient will be collected including the
pre-dose blood samples, throughout the whole study duration.
Food and Fluid Restrictions: Food and fluid
instruction needs to be followed as per protocol.
Assessments: As this drug may cause
suicidal behaviour and extrapyramidal side effects, evaluation of suicidal
behaviour (using C-SSRS scale), neuroleptic malignant syndrome and any extra
pyramidal adverse event assessment will be performed at regular interval during
the study.
Additionally, CGI evaluation will also be performed to evaluate
changes in the disease condition during the study. Other
standard safety assessments like vital signs, physical examination, AE
assessment, and laboratory tests will be performed.