Bioequivalence Fasting Study in Patients

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.

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Asenapine Sublingual Tablets 10 mg; Drug: Asenapine Sublingual Tablets 10 mg

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• India
  • Gujurat
    • Junagadh, Gujurat, India, 362 001
      • Shri Hatkesh Healthcare Foundation
    • Surat, Gujurat, India, 395 001
      • Divyam Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Asenapine Sublingual Tablets; Asenapine Sublingual Tablets, 10 mg. Twice daily for a period of 7 days	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; Drug: Asenapine Sublingual Tablets 10 mg; Round, white to off-white sublingual tablets, with "10" on one side within a circle
Active Comparator: Saphris Subligual Tablets; Asenapine Sublingual Tablets, 10 mg. Twice daily for 2 periods of 7 days each.	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; Drug: Asenapine Sublingual Tablets 10 mg; Round, white to off-white sublingual tablets, with "10" on one side within a circle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Cmax	Maximum measured plasma concentration over the steady state doing interval	Dosing interval on day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmin	Minimum measured plasma concentration over the steady state dosing interval	Dosing interval on day 7
Tmax	Time the maximum measured plasma concentration over the steady state dosing interval	Dosing interval on day 7
Cavg	Average calculated plasma concentration over the steady state dosing interval	Dosing interval on day 7
Percentage Fluctuation	[Cmax - Cmin/ Cavg] x 100	Dosing interval on day 7

Collaborators and Investigators

• Sponsor: Amneal Pharmaceuticals, LLC
• Collaborators: Accutest Research Laboratories (I) Pvt. Ltd.
• Investigators: Principal Investigator: Ashutosh Jani, MD, Accutest Reserach laboratories (i) Pvt. Ltd.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: February 25, 2014
• First Submitted That Met QC Criteria: February 25, 2014
• First Posted (Estimate): February 27, 2014

Study Record Updates

• Last Update Posted (Estimate): June 27, 2014
• Last Update Submitted That Met QC Criteria: June 25, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Asenapine
• Other Study ID Numbers: ARL/CT/13/003; CTRI No. CTRI/2013/11/004152 (Other Identifier: Clinical Trials Registration India)