20 January 2013
ASX ANOUNCEMENT
RESULTS OF PIVOTAL PHASE III CLINICAL TRIAL
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Methoxyflurane inhalation demonstrated to be highly effective analgesic.
Methoxyflurane provided clinically-significant pain reduction.
Demonstrated safety of methoxyflurane for the treatment of acute pain.
Primary Endpoint and Objective of the study was met.
All Secondary Endpoints and Objectives were met.
MVP Comment
Medical Developments International is delighted to announce that it has completed its Pivotal
Phase III Clinical Trial which comprised a randomised, 300 patient, double-blind, multi-centre,
placebo-controlled study to evaluate the efficacy and safety of methoxyflurane (Penthrox™) for
the treatment of acute pain in patients presenting to an Emergency Department with minor
trauma.
The success of MVP’s Pivotal Phase III study is a very significant milestone for our company.
The study provides us with clinical evidence of the safety and efficacy of Penthrox and will
become a critical component of our regulatory strategy to introduce Penthrox into new markets
internationally and in particular, Western Europe.
MVP will now proceed with its regulatory strategy in Europe. We expect to submit our
Marketing Authorisation Application for selected countries in Europe as scheduled before April
2013. In addition, we intend to update countries currently considering the registration of
Penthrox with this trial data and outcomes.
Details for the Clinical Trial are as follows
1. The study was a Pivotal Phase III trial.
2. Primary Endpoint: To evaluate the short-term efficacy of methoxyflurane for the
treatment of acute pain in patients presenting to an Emergency Department (ED) with
minor trauma.
The Primary Objective and Endpoint was met.
3. Secondary Endpoints: To evaluate the:
a) Safety of methoxyflurane for the treatment of acute pain in patients presenting
to an ED with minor trauma;
b) Efficacy of methoxyflurane for the treatment of acute pain in patients with minor
trauma during their time in the ED.
Both Secondary Objectives and Endpoints were met.
4. Efficacy conclusions:
a) There was a highly significant difference between the methoxyflurane and
placebo group (p<0.0001) in the analysis of the change of VAS pain intensity
score from baseline.
b) There was a highly significant difference (p=0.0002) between the
methoxyflurane and placebo groups in the use of rescue medication (requested
by the patient) within 20 minutes of the start of treatment.
c) The median time to first pain relief for the methoxyflurane group was 4 minutes.
This compares with the median time to onset of meaningful pain relief for
intranasal fentanyl of 11 minutes and 16 minutes for oromucosal fentanyl. A
total of 126 patients (84.6%) in the methoxyflurane group experienced their first
pain relief with 1-10 inhalation.
d) Overall, the study results demonstrate a highly significant treatment effect by all
efficacy analysis.
5. Safety conclusions:
a) The study treatment (methoxyflurane or placebo) was well tolerated during the
study with no deaths and only one serious Treatment Emergent Adverse Event
(TEAE) which was unrelated to the study or the study drug.
b) The number of patients experiencing TEAEs leading to the withdrawal of study
treatments was lower in the methoxyflurane group (1.3%) compared to the
placebo group (2.0%).
c) There was little change in systolic blood pressure, diastolic blood pressure,
respiratory rate, heart rate, heart rhythm (regular and irregular rhythm
specified) between the evaluation in patients in the methoxyflurane group. The
results were comparable to that of the placebo group.
d) Overall, methoxyflurane was well tolerated with the majority of adverse
reactions being mild, transient and in line with anticipated pharmacological
action. Patients successfully completed treatment with no relevant difference in
incidence, severity or proportion of events leading to withdrawal between the
methoxyflurane and placebo groups.
6. Global Medication Performance
The Global Medication Performance (GMP) is the assessment by the patient, physician
and research nurse following the completion of the Emergency Department visit.
a) 83.3% of patients assessed the GMP as good, very good or excellent.
b) 83.7% of clinicians assessed the GMP as good, very good or excellent.
c) 79.9% of research nurses assessed the GMP as good, very good or excellent.
7. The study was conducted according to the International Conference on Harmonization
(ICH) guidance on Good Clinical Practice (GCP), any local guidelines, and the Declaration
of Helsinki (with all current additions).
8. The first patient enrolled in the trial was on 05 August 2011 and the last patient
completed was 26 July 2012.
9. The trial was completed on time and on budget.
10. The trial was conducted at 6 sites across the United Kingdom.
11. Methodology: Randomised, double-blind, placebo controlled multicentre clinical study
comparing methoxyflurane self-administered as required via the Penthrox™ inhaler at a
dose of up to 6ml to placebo for the treatment of acute pain (randomisation in a
1:1 ratio).
12. Number of Patients (Planned and Analysed):
Planned: Three hundred (300) patients were to be randomised; 150 to receive
methoxyflurane and 150 to receive placebo, 90 of which would be adolescent patients.
Actual: Three hundred (300) patients were randomised to receive treatment; 149
patients received methoxyflurane and 149 patients received placebo; 2 randomised
patients did not receive treatment, 95 patients were adolescent patients.
13. Diagnosis and Main Criteria for Inclusion:
Patients aged ≥ 12 years who presented to the ED with acute pain associated with minor
trauma where trauma referred to “a physical wound or injury” such as a fractures,
lacerations, burns, dislocations, contusions or injury due to foreign bodies;
Evidence of signed and dated informed consent document(s) indicating that the patient
(and/or a parent/legal guardian) had been informed of all pertinent aspects of the
study;
Patients were required to register a pain score ≥ 4 to ≤ 7 as measured using Numerical
Rating Scale (NRS) at the time of admission, due to minor trauma.
14. Duration of Treatment:
It was anticipated each Penthrox inhaler would provide up to 1 hour’s pain relief when
used intermittently. A second inhaler was made available providing an estimated 2
hours of pain relief.
15. Study Report Conclusion
a. The primary Endpoint and Objective was met.
b. All Secondary Endpoints and Objectives were met.
c. Overall the study showed methoxyflurane inhalation to be a highly effective
analgesic in patients presenting with acute pain due to the various types of
injuries commonly encountered in the emergency departments.
d. The study showed methoxyflurane provided clinically significant pain
reduction, defined as a reduction in the pain severity of greater than 30% of
the initial pain score [Farrar et.al 2001].
e. The study showed the safety of methoxyflurane for the treatment of acute
pain.
f. Methoxyflurane administration through the PenthroxTM inhaler was shown to
be a simple to use, portable, safe, effective and rapidly working analgesic.
David Williams
Chairman
Medical Developments International Ltd
+61 414 383 593
John Sharman
Chief Executive Officer
Medical Developments International Ltd
+61 3 9547 1888