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

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

A study to assess bioavailability of a single dose of MR902 and to assess the effect of food on absorption

Study Overview

• Status: Completed
• Conditions: Opioid Substitution Treatment
• Intervention / Treatment: Drug: MR902; Drug: IR morphine sulphate

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.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MR902 50/0.5 mg; MR902 50/0.5 mg PR tablets, single dose oral	Drug: MR902
Experimental: MR902 200/2 mg; MR902 200/2 mg PR tablets, single dose oral	Drug: MR902
Active Comparator: IR morphine sulphate 10 mg/5mL solution; IR morphine sulphate 10 mg/5mL solution, single dose oral	Drug: IR morphine sulphate; 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

Collaborators and Investigators

• Sponsor: Mundipharma Research Limited

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: May 10, 2016
• First Submitted That Met QC Criteria: May 13, 2016
• First Posted (Estimate): May 16, 2016

Study Record Updates

• Last Update Posted (Estimate): May 16, 2016
• Last Update Submitted That Met QC Criteria: May 13, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: MR902-1501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO