SPD544 High Strength Bioequivalence Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess bioequivalence of 2 capsule strengths.

Detailed Description
-----------------
This will be a randomised, open-label, two-period, single dose, crossover bioequivalence study in healthy subjects under fasting conditions to assess bioequivalence of 1 x 60 mg capsule methylphenidate compared to 2 x 30 mg capsules methylphenidate. Pharmacokinetics and safety will be assessed.

Official Title
-----------------
Phase 1,Randomized,Open-Label,Two Period Single Dose Crossover Bioequivalence Study of Two Capsule Strengths of SPD544 In Healthy Volunteers.

Conditions
-----------------
ADHD

Intervention / Treatment
-----------------
* Drug: SPD544
* Drug: Methylphenidate hydrochloride


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Healthy subjects, aged 18-55 years inclusive at the time of consent. Subject must be willing to comply with applicable contraceptive requirements of the protocol and be: Male, or Non-pregnant, non-lactating female who must be >90 days post-partum or nulliparous. Body Mass Index (BMI) between 18.5 and 30.0kg/m² inclusive. This inclusion criterion will only be assessed at the Screening visit. Satisfactory medical assessment with no clinically significant or relevant abnormalities in medical history, physical examination, vital signs, ECG, and clinical laboratory evaluation (haematology, biochemistry, urinalysis) as assessed by the Investigator. Ability to provide written, personally signed and dated informed consent to participate in the study. An understanding, ability and willingness to fully comply with study procedures and restrictions. Ability to swallow all investigational medicinal products (IMPs). Exclusion criteria: Current or recurrent disease (e.g., cardiovascular, renal, liver, gastrointestinal, malignancy or other conditions) that could affect the action, absorption, or disposition of the IMPs, or could affect clinical or laboratory assessments. Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully comply with the requirements of the study or complete the study, or any condition that presents undue risk from the IMPs or study procedures. Current use of any medication (including prescription, over-the-counter [OTC], herbal, or homeopathic preparations) with the exception of hormone replacement therapy or hormonal contraceptives and/or an occasional dose of nonsteroidal anti-inflammatory (NSAID), or paracetamol (current use is defined as use within 14 days of first dose of IMP). History of hypertension or a resting sitting systolic blood pressure >139mmHg or diastolic blood pressure >89mmHg. History of seizure (other than infantile febrile seizures), any tic disorder, or a current diagnosis and/or family history of Tourette's Disorder. Known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, transient ischaemic attack or stroke, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug. Family history of sudden cardiac death or ventricular arrhythmia. Known cerebrovascular disorders such as cerebral aneurysm, vascular abnormalities including vasculitis or history of stroke. Diagnosis of glaucoma. Diagnosis of phaeochromocytoma. Current abnormal thyroid function, as defined as abnormal screening thyroid stimulating hormone (TSH) and thyroxine (T4). Current marked anxiety, tension and/or agitation. History of alcohol or other substance abuse within the last year. A positive screen for alcohol or drugs of abuse at Screening or Day -1 of Treatment Period 1. Male subjects who consume more than 3 units of alcohol per day. Female subjects who consume more than 2 units of alcohol per day. A positive human immunodeficiency virus (HIV) antibody screen, Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody screen. Use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing products in any form (e.g., gum, patch) within 30 days prior to the Screening visit. Routine consumption of more than 300mg of caffeine per day or subjects who experience caffeine withdrawal headaches or have a history of caffeine withdrawal headaches. Donation of blood or blood products (e.g., plasma or platelets) within 90 days prior to the first dose of IMP.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPD544 (Equasym XL)<br> | Drug: SPD544<br>* two 30mg capsules, single oral dose<br>* Other names: Equasym XL;|
| Experimental: Methylphenidate hydrochloride (Metadate CD )<br> | Drug: Methylphenidate hydrochloride<br>* one 60mg capsule, single oral dose<br>* Other names: Metadate CD;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Steady-state Plasma Concentration-time Curve (AUC 0-t) for Methylphenidate Hydrochloride (MPH) Using Two Different Formulations (Equasym XL and Metadate CD) | AUC 0-t is the area under the plasma concentration versus time curve from time 0 to the time of last quantifiable concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body. | predose and 0.5, 1.0, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20 and 24 hours post-dose | 
| Maximum Plasma Concentration (Cmax) for MPH Using Two Different Formulations (Equasym XL and Metadate CD) | Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated. | predose and 0.5, 1.0, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20 and 24 hours post-dose | 
| Time of Maximum Plasma Concentration (Tmax) for MPH Using Two Different Formulations (Equasym XL and Metadate CD) | Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached. | predose and 0.5, 1.0, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20 and 24 hours post-dose |