Bioequivalence Fasting Study in Patients

Schizophrenia Clinical Trial

Official title:

A Multicentric, Open Label, Randomized, Balanced, Two Treatment, Three Period, Three Sequence, Crossover, Multiple Dose, Steady State Bioequivalence Study of Asenapine Sublingual Tablets, 10 mg Manufactured by AMNEAL PHARMACEUTICALS, USA With Reference Product SAPHRIS® (Asenapine) Sublingual Tablets, 10 mg Manufactured by Catalent UK Swindon Zydis Ltd., Blagrove, Swindon, Wiltshire, SN5 8RU, UK; Distributed by Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, 08889, USA in Adult Human Male & Female Patients Under Fasting Condition.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02072954
• Other study ID #: ARL/CT/13/003
• Secondary ID: CTRI No. CTRI/20
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: February 25, 2014
• Last updated: June 25, 2014
• Start date: November 2013
• Est. completion date: June 2014

Study information

• Verified date: June 2014
• Source: Amneal Pharmaceuticals, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

To compare and evaluate the oral bioavailability of Asenapine Sublingual Tablets, 10 mg manufactured by AMNEAL PHARMACEUTICALS, USA with SAPHRIS® (asenapine) sublingual tablets, 10 mg.

Description:

To compare and evaluate the oral bioavailability of Asenapine Sublingual Tablets, 10 mg manufactured by AMNEAL PHARMACEUTICALS, USA with SAPHRIS® (asenapine) sublingual tablets, 10 mg following a multiple-dose administration in adult human patients who are receiving a stable twice daily dose of asenapine maleate EQ 10 mg base.

To monitor the safety and tolerability of a multiple doses of asenapine sublingual tablets 10 mg in adult human patients who are receiving a stable twice daily dose of asenapine maleate EQ 10 mg base.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: June 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Adult patients of either sex with age between 18 to 65 years (both inclusive) and have been taking a stable dose of asenapine maleate sublingual tablet, EQ 10 mg base twice daily therapy for at least three months.

• Willing and able to comply with study visit schedule and other protocol requirements as indicated by signed written informed consent witnessed by a legally acceptable representative.

• Females of childbearing (who has not completed 01 year after menopause & have not gone through hysterectomy or bilateral tubal ligation) potential must have a negative pregnancy test (at screening, before randomization and before check-in to housing) as well as must be non-lactating at screening and must agree to use an effective contraceptive method during study.

Exclusion Criteria:

• History of allergic or adverse reactions to asenapine maleate or olanzapine as judged by investigator

• If consuming tobacco orally (spit tobacco, gutka, pan masala, pan, etc.)

• A history of severe hepatic impairment, drug induced leukopenia/ neutropenia, congenital prolongation of the QT interval, cardiac arrhythmias, myocardial infarction or unstable heart disease

• Concurrent primary psychiatric or neurological diagnosis, including organic mental disorder, severe tardive dyskinesia, or idiopathic Parkinson's disease

• Abnormal laboratory results

• A history of granulocytopenia or myeloproliferative disorders (drug-induced or idiopathic)

• A medical or surgical condition that might interfere with the absorption, metabolism, or excretion of asenapine maleate

• History of multiple syncopal episodes

• History of epilepsy or risk for seizures

• Any condition/ Abnormal baseline findings that in the investigators' judgment might increase the risk to the patient (e.g. Significant orthostatic hypotension defined as 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) or decrease the chance of obtaining satisfactory data needed to obtain the objective of the study.

• A history of alcohol or drug dependence by DSM-IV criteria during the 6-month period immediately prior to study entry

• Positive tests for drug or alcohol abuse at screening or baseline

• Use of any of the following medication in the 14 days preceding enrollment: Strong CYP3A4 inhibitors, Strong CYP3A4 inducers, CYP1A2 inhibitors, Antihypertensive medication or any medication that might predispose to orthostatic hypotension, Drugs known to suppress bone marrow function, medications known to prolong the QTc interval.

• Participation in any other clinical study or receipt of treatment with any investigational drug or device within 1 month prior Screening.

• Blood donation/ loss exceeding 550 mL within last 90 days.

• Any expected changes in concomitant medications during the period of study

• Compliance with outpatient medication schedule not expected

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Asenapine Sublingual Tablets 10 mg
White to off-white, round, uncoated,unscored, flat-faced radius edge tablet. Debossed with A on one side and 17 on the other side
• Asenapine Sublingual Tablets 10 mg
Round, white to off-white sublingual tablets, with "10" on one side within a circle

Locations

Country	Name	City	State
India	Shri Hatkesh Healthcare Foundation	Junagadh	Gujurat
India	Divyam Hospital	Surat	Gujurat

Sponsors (2)

Lead Sponsor	Collaborator
Amneal Pharmaceuticals, LLC	Accutest Research Laboratories (I) Pvt. Ltd.

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC 0-tau	The area under plasma concentration versus time curve, over the steady state dosing interval, calculated using linear trapezoidal method.	Dosing interval on day 7	No
Primary	Cmax	Maximum measured plasma concentration over the steady state doing interval	Dosing interval on day 7	No
Secondary	Cmin	Minimum measured plasma concentration over the steady state dosing interval	Dosing interval on day 7	No
Secondary	Tmax	Time the maximum measured plasma concentration over the steady state dosing interval	Dosing interval on day 7	No
Secondary	Cavg	Average calculated plasma concentration over the steady state dosing interval	Dosing interval on day 7	No
Secondary	Percentage Fluctuation	[Cmax - Cmin/ Cavg] x 100	Dosing interval on day 7	No