Study to Assess Pharmacokinetic (PK), Bioavailability & Food Effect of MR902 Compared With Immediate Release (IR) Morphine Sulphate Oral Solution

Study Overview
=================
Brief Summary
-----------------
A study to assess bioavailability of a single dose of MR902 and to assess the effect of food on absorption

Detailed Description
-----------------
Volunteers will receive a single dose of the investigational drug on 2 occasions and a reference drug on 1 occasion. Volunteers will be randomised to one of two groups, each group receiving a different dose strength of MR902 in fed and fasted state. The study involves a screening visit 21 days before first dosing and 3 overnight stays in 3 study periods, and a post-study medical visit. Volunteers will receive naltrexone to reduce anticipated opioid side effects.

Official Title
-----------------
2-cohort, 3-part, Open-label, Randomised, Single Dose, Crossover Study in Healthy Subjects to Compare PK & Bioavailability of a Single Dose, in Fed and Fasted State, of MR902 Prolonged Release (PR) Tablets With Immediate Release (IR) Morphine Sulfate Oral Solution

Conditions
-----------------
Opioid Substitution Treatment

Intervention / Treatment
-----------------
* Drug: MR902
* Drug: IR morphine sulphate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy and free of significant abnormal findings as determined by medical history, physical examination, vital signs, laboratory tests and ECG. Body weight ranging from 55 to 100 kg and a BMI ≥ 18.5 and ≤ 30.0. Willing to eat all the food supplied throughout the study. The subject's primary care physician has confirmed within the last 12 months of first dosing that there is nothing in their medical history that would preclude their enrolment into a clinical study. Exclusion Criteria: Female subjects who are pregnant or lactating. Any history of drug or alcohol abuse, misuse, physical or psychological dependence. Any history of conditions that might interfere with drug absorption, distribution, metabolism or excretion. Use of opioid or opioid antagonist-containing medication in the past 30 days. Any history of frequent nausea or vomiting regardless of etiology. Any history of seizures or symptomatic head trauma. History of respiratory depression, hypoxia or elevated carbon dioxide levels in the blood. History of paralytic ileus, gastrointestinal disease or other clinically significant gastrointestinal problems. Participation in a clinical drug study during the 90 days preceding the initial dose in this study. Any significant illness during the 4 weeks preceding entry into this study. Use of any medication including vitamins, herbal and/or mineral supplements during the 7 days preceding the initial dose or during the course of this study (with the exception of the continued use of HRT and contraceptives). History of smoking within 60 days of IMP administration and refusal to abstain from smoking during the study.

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: MR902 50/0.5 mg<br>MR902 50/0.5 mg PR tablets, single dose oral | Drug: MR902<br> <br> |
| Experimental: MR902 200/2 mg<br>MR902 200/2 mg PR tablets, single dose oral | Drug: MR902<br> <br> |
| Active Comparator: IR morphine sulphate 10 mg/5mL solution<br>IR morphine sulphate 10 mg/5mL solution, single dose oral | Drug: IR morphine sulphate<br> <br> * Other names: IR morphine sulphate 10 mg/mL solution;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure the observed maximum plasma or serum concentration after administration (Cmax) | PK plasma parameters | Pre-dose to 24 hours post-dose | 
| Measure the area under the concentration-time curve from zero up to a definite time t after administration (AUCt) | PK Plasma Parameters | Pre-dose to 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| measurement of Pharmacokinetic parameter Area under the curve to infinity after administration (AUCINF) | PK plasma parameters | Pre-dose to 24 hours post-dose | 
| measurement of Pharmacokinetic parameter time to maximum concentration after administration (tmax) | PK plasma parameters | Pre-dose to 24 hours post-dose | 
| measurement of Pharmacokinetic parameter of elimination rate after administration (LambdaZ,) | PK plasma parameters | Pre-dose to 24 hours post-dose | 
| Measurement of Pharmacokinetic parameter elimination of half life after administration ( t1/2Z) | PK plasma parameters | Pre-dose to 24 hours post-dose | 
| Measurement of heart rate | Vital signs measurements | Pre-dose to 24 hours post-dose | 
| Measurement of blood pressure | vital signs measurement | pre-dose to 24 hours post-dose | 
| Measurement of respiration rate | vital signs measurement | pre-dose to 24 hours post-dose | 
| Measurement of temperature | vital signs measurement | pre-dose to 24 hours post-dose | 
| Measurement of Saturation Pulse Oxygen (SP02) | vital signs measurement | pre-dose to 24 hours post-dose |