1. RALFINAMIDE
EFFICACY OF RALFINAMIDE IN PATIENTS WITH THIRD MOLAR
POST-EXTRACTION DENTAL PAIN.
by RAHUL
challarahul77@gmail.com

2. INTRODUCTION;
The objectives of this study are to evaluate the safety, tolerability and preliminary
evidence of analgesic efficacy of orally administered ralfinamide at a target dose of
480 mg/day, compared to placebo, in patients with third molar, post-extraction,
dental pain.
Gender Both
Ages 18 Years and older
Accepts No
Healthy
Volunteers

3. Study Randomised,
Type Placebo-controlled,
Double-blind Study
Drug: Ralfinamide
Study Phase 2
Phase
Condition Post-Extraction Dental Pain

4. STUDY
DURATION
STUDY
POPULATION A minimum of 180 patients (90 patients per group)
Randomised (1:1)
20 centres, in 2 countries (India and Romania)

5. ELIGIBILITY
CRITERIA Inclusion Criteria:
Patient is ≥18 years of age. If female, the patient must be post-
menopausal for at least 12 months, surgically sterilized or have
undergone hysterectomy.
Patients must be scheduled to undergo extraction of one or more third
molar(s), of which at least one must be either partially or completely
impacted in the mandibular bone.
Exclusion Criteria:
If female, the patient is of childbearing potential, pregnant or lactating.
Women less than 50 years of age will be required to have a pregnancy
test at screening.
Patient has a chronic pain condition requiring continuous treatment
with analgesics.
History of alcohol or drug abuse
Severe thyroid dysfunction, rheumatoid arthritis or vasculitis.
Second- or third-degree atrioventricular block or sick sinus syndrome,
uncontrolled atrial fibrillation, severe or unstable angina, congestive
heart failure, myocardial infarction within 3 months of the screening visit,
significant ECG abnormalities

6. Screening a) All laboratory results must be available before the decision is made
(Visit 1: Day to enrol the patient and start treatment at Visit 2.
-8) b) vital signs – height, body weight, temperature, pulse, systolic and
diastolic BP, respiratory rate.
c) medical history
d) physical examination
e) neurological examination
Run-in period a) Eligible patients will enter a 3-day run-in period during which all
(Days –8 to –6) screening evaluations must be completed
b) Patients with clinically significant abnormal laboratory values that
do not normalize prior to Visit 2 will not be randomised to the
treatment phase
Pre-Surgery (Dose Level 1):
Treatment Ralfinamide 320 mg/day (160 mg b.i.d.); or
Period (Visit 2: • Placebo.
Days –5 to –1)

7. Baseline higher dose of study medication.
(Visit 3: Day 0) Dose Level 1: 4 tablets; if on Dose Level 0: 2 tablets.
Safety evaluations performed pre-surgery
(Day 0); efficacy evaluated in clinic for 6 hr post-surgery (Day 1); patient
dispensed medication and given pain diary to complete at home.
Post-Surgery 6-hr evaluation period during.
Treatment
period Any adverse events that occur during this period must be recorded.
(Visits 4, 5 and patients will be required to complete the PGART
6: Days 1, 2
and 3) On Day 3, the Investigator will perform the final evaluations when the
patient returns to the clinic.

8. EFFICACY ANALYSIS
PRIMARY The Cox regression model will be adopted to evaluate
EFFICACY treatment effect
ANALYSIS
Results will be reported as hazard ratios (HRs) with associated two-
tailed 95% confidence intervals.
SECONDARY Wilcoxon Rank Sum test & whilst treatment
EFFICACY
ANALYSIS Differences will be reported as Hodges-Lehmann estimates with
associated non parametric 95%

9. FINANCIAL NEWRON Pharmaceuticals.
AGREEMENT
REGULATORY This study will be conducted in accordance with the Declaration of
REQUIREMENTS Helsinki and the ICH E6 Guideline
(Good Clinical Practice).
INSURANCE
NEWRON will provide insurance coverage for damages emerging
POLICY from the trial and involving the
subjects treated

10. ADMINISTRATIVE INFORMATION
PROTOCOL
NUMBER NW-1029/002/II/2007
SPONSOR:
Newron Pharmaceuticals S.p.A.
via L. Ariosto 21, 20091 Bresso (MI), Italy
PROTOCOL YES
APPROVAL
14 MAY 2007