A multicenter open label randomized balanced two treatment two period two sequence crossover multiple dose bioequivalence study of Asenapine Maleate EQ 10 mg base sublingual spray of Navinta LLC USA with SAPHRIS® (Asenapine) sublingual tablets EQ 10 mg base Distributed by Allergan USA Inc. Irvine CA 92612 in adult patients with schizophrenia or bipolar I disorder under fasting conditions
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Navinta LLC
- Enrollment
- 24
- Locations
- 4
- Primary Endpoint
- To demonstrate the bioequivalence at steady
Study Overview
Brief Summary
Patient who have been taking a stable dose of sublingual tablet, EQ 10 mg base twice daily therapy for at least three months will be eligible for the study participation. Patients who are eligible to participate in the study based on screening assessments would receive their own established dose twice daily (at least 12 hours apart) for 14 days in a crossover design. There will be no wash-out period between two study periods.
In period-I (from day 1 to day 7), patients will receive either the Test product or the reference product every 12 hours for 7 days.
In period-II (from day 8 to day 14), patients will be switched to another product for a second period of 7 days. After the study is completed (after last PK sample collection on day 14), patients could be continued on twice daily dose of asenapine maleate EQ 10 mg base using an approved asenapine maleate product as prescribed by their clinicians. The evening dose of asenapine on day 7 & day 14 will be administered after last PK sample collection of 12 hours. Blood samples for PK assessment will be collected at various time points in both the periods and plasma concentration of asenapine will be quantified using validated analytical method.
Study Design
- Study Type
- Interventional
- Allocation
- Computer generated randomization
- Masking
- Open Label
Eligibility Criteria
- Ages
- 18.00 Year(s) to 65.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •Men and non-pregnant women (both inclusive) having clinical diagnosis of Schizophrenia or Bipolar I disorder.
- •Patients should be appropriate candidates for asenapine maleate sublingual tablet or spray EQ 10 mg base twice daily therapy and have been receiving a stable dose of asenapine maleate sublingual tablet EQ 10 mg base twice daily therapy for at least three months prior to screening.
- •Adequate hematological parameters hepatic and renal function at screening defined by: Total white blood cell count more than 4000/cmm ANC more than equal to 2000/mm3 Platelet count more than equal to 75000/mm3 Haemoglobin more than equal to 9.0 gm/dL Bilirubin less than and equal to 1.5 X ULN (upper limit of normal) AST/ALT less than an equal to 3 X ULN S.
- •creatinine less than an equal to 1.5 X ULN or creatinine clearance more than an equal to 60 ml/min
- •Patients should be otherwise healthy as determined by physical examination medical history and routine hematologic and biochemical tests.
- •Willing and able to comply with housing restrictions and other protocol requirements as indicated by signed written informed consent witnessed by a legally acceptable representative.
- •Sexually active women unless surgically sterile (at least 6 months prior to study drug administration) or amenorrhoea for at least 12 consecutive months must agree to use an effective method of avoiding pregnancy (including oral transdermal or implanted contraceptives [any hormonal method in conjunction with a secondary method] intrauterine device female condom with spermicide diaphragm with spermicide absolute sexual abstinence use of condom with spermicide by sexual partner) from screening during the study and till the study completion (i.e. post study safety assessment after last PK sample collection in period II).
- •And Sexually active women must have a negative pregnancy test (at screening before check-in on day 0) as well as must be non lactating at the time of screening.
- •No participation in any clinical study within the past 60 days.
Exclusion Criteria
- •A history of allergic or adverse reactions to asenapine maleate or any comparable or similar product.
- •A history of severe hepatic impairment, drug induced leukopenia/neutropenia.
- •Concurrent (other than Schizophrenia or Bipolar I disorder) primary psychiatric or neurological diagnosis, including organic mental disorder, severe tardive dyskinesia, or idiopathic Parkinson’s disease, cognitive and motor impairment.
- •A history of granulocytopenia or myelo proliferative disorders (drug-induced or idiopathic).
- •Patient with the history or presence of significant orthostatic hypotension (i.e. a drop in systolic blood pressure of 30 mm Hg or more and/or a drop in diastolic blood pressure of 20 mm Hg or more on standing) at the time of screening.
- •Concurrent use of antihypertensive medication or any medication that might predispose to orthostatic hypotension.
- •A medical or surgical condition that might interfere with the absorption, metabolism, or excretion of asenapine maleate.
- •A history of epilepsy or risk for seizures.
- •Concurrent use of other drugs known to suppress bone marrow function.
- •Expected changes in concomitant medications during the period of study.
- •Positive tests for drug or alcohol abuse at screening or baseline.
- •A history of alcohol or drug dependence by Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) or later criteria during the 6-month period immediately prior to study entry.
- •Compliance with outpatient medication schedule not expected.
- •History of multiple syncopal episodes or stroke.
- •Patients with dementia related psychosis.
- •Patients with a history of Neuroleptic Malignant Syndrome (NMS).
- •Presence of uncontrolled metabolic disorders including uncontrolled diabetes mellitus (Fasting blood glucose levels more than an equal to 160 mg/dl and HbA1c more than an equal to 8 %), Serum total cholesterol more than an equal to 300 mg/dl and fasting serum triglyceride levels more than an equal to 300 mg/dl.
- •Patients with the following cardiac conditions: Recent myocardial infarction (less than 12 months) Persistent (3 consecutive electrocardiograms [ECGs] performed 2 to 5 minutes apart) prolongation of the QTc(Fridericia) interval to more than 480 msec; History of cardiac arrhythmias or presence of circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including: bradycardia, cardiac arrhythmias, hypokalemia or hypomagnesemia, concomitant use of other drugs that prolong the QTc interval; and presence of congenital prolongation of the QT interval (QTc more than 450 ms)
- •Patients with clinically significant hyperprolactinemia or with possible prolactin dependent tumor.
- •Use of any of the following medications within 14 days or at least five half-lives have not been passed between last dose of the previous medication and first dose of the study medication, preceding enrollment including but not limited to: Strong CYP1A2 Inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin etc.).
- •CYP2D6 Substrates and Inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline etc).
- •Drugs known to prolong QTc including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), antipsychotic.
Outcomes
Primary Outcomes
To demonstrate the bioequivalence at steady
Time Frame: A total of 36 blood samples each of 07 mL will be collected during the study for PK analysis. The predose blood sample will be | scheduled to be collected within 5 minutes before morning dosing on days 5 6 7 in period I and days 12 13 14 in period II of the study. | On day 7 & day 14, the post-dose blood samples will be drawn at | 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, | 8.00, 10.00, 12.00 hour following morning drug administration
state of Asenapine Maleate EQ 10 mg base sublingual spray of Navinta LLC, USA with SAPHRIS® (Asenapine) sublingual tab EQ 10 mg base Distributed by Allergan USA Inc. Irvine CA 92612 in adult patients with schizophrenia or bipolar I disorder under fasting conditions.
Time Frame: A total of 36 blood samples each of 07 mL will be collected during the study for PK analysis. The predose blood sample will be | scheduled to be collected within 5 minutes before morning dosing on days 5 6 7 in period I and days 12 13 14 in period II of the study. | On day 7 & day 14, the post-dose blood samples will be drawn at | 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, | 8.00, 10.00, 12.00 hour following morning drug administration
To monitor the safety and tolerability profile of the study formulations.
Time Frame: A total of 36 blood samples each of 07 mL will be collected during the study for PK analysis. The predose blood sample will be | scheduled to be collected within 5 minutes before morning dosing on days 5 6 7 in period I and days 12 13 14 in period II of the study. | On day 7 & day 14, the post-dose blood samples will be drawn at | 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, | 8.00, 10.00, 12.00 hour following morning drug administration
Secondary Outcomes
- To monitor the safety and tolerability profile of the study formulations(Blood pressure pulse rate and body temperature shall be)