A Comparative, Randomized, Double-blind, 3-arm Parallel, Phase III Study to Evaluate the Efficacy and Safety of a Fixed Dose Combination of Nefopam/Paracetamol Taken Orally in Moderate to Severe Pain After Impacted Third Molar Extraction
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 321
- 试验地点
- 18
- 主要终点
- Ranked Endpoints : 1. Sum of Pain Intensity Differences at 6 Hours (SPID0-6h)
研究概览
简要总结
This study aims to evaluate the analgesic efficacy of single and multiple doses of a new fixed dose combination of nefopam hydrochloride 30 mg and paracetamol 500mg taken orally in comparison to each single component.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double-blind. Participants, investigators, and all persons involved in the conduct, data management, and analysis of the study will be fully blinded to the participant's treatment.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patient aged from 18 years up to 65 years,
- •Patient scheduled to undergo the surgical removal of at least one fully or partially impacted third mandibular molar requiring bone removal under short-acting local anaesthetic (mepivacaine or lidocaine) with or without vasoconstrictor,
- •Patient weighing > 50 kg,
- •Patient who has signed a written informed consent prior to any study-related procedures.
- •Additional inclusion criteria after surgery (randomization):
- •Patient experiencing moderate to severe pain within 4 hours after the dental extraction, defined by a baseline pain intensity Visual Analogic Scale (VAS) score ≥ 50 mm,
- •Third molar extraction(s) completed without any immediate complication, that in the opinion of the investigator, would interfere with the study conduct and/or assessments (e.g., suspected neurosensory complication, incomplete removal of tooth)
排除标准
- •Patient treated by analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs) within 3 days preceding the day of randomization or within 5 times the elimination half-life whichever the longest,
- •Woman with positive results on a urine pregnancy test or breastfeeding woman or woman of childbearing potential without an effective contraception,
- •Patient with a history of convulsive disorders,
- •Patient taking mono-amine-oxidase (MAO) inhibitors (including but not limited to selegiline, isocarboxazid, tranylcypromine, phenelzine...),
- •Patient with an abnormal cardiac condition: medically significant disorders of cardiac rate and/or rhythm,
- •Patient with known anaemia,
- •Patient with known pulmonary disease,
- •Patient with known active gastric or duodenal ulcer or a history of recurrent gastrointestinal ulcer/bleeding,
- •Patient with known glaucoma,
- •Patients with a prostatic hyperplasia or urinary retention,
- •Patient with current or chronic history of liver disease, or known hepatic or biliary abnormalities,
- •Patient with a current or chronic history of severe renal impairment (glomerular filtration below 30 mL/min),
研究组 & 干预措施
FDC nefopam hydrochloride 30 mg / paracetamol 500 mg (X2)
Each dose: 2 tablets (included in masking capsule)
干预措施: nefopam hydrochloride 30mg / paracetamol 500mg X2 (Combination Product)
Paracetamol 500 mg (X2)
Each dose: 2 tablets (included in masking capsule)
干预措施: Paracetamol 500 Mg Oral Tablet X2 (Drug)
Nefopam hydrochloride 30 mg (X2)
Each dose: 2 tablets (included in masking capsule)
干预措施: Nefopam HCl 30 MG Oral Tablet X2 (Drug)
结局指标
主要结局
Ranked Endpoints : 1. Sum of Pain Intensity Differences at 6 Hours (SPID0-6h)
时间窗: 6 hours post-dose
Pain intensity difference (PID) will be calculated using the score of pain intensity assessed by the patient at defined time points (T30, T45, T60, T90, T120, T150, T180, T240, T300, T360 min,) after the first Investigational Medicinal Product (IMP) intake and/or right before first intake of rescue medication using a 100-mm Visual Analogic Scale (VAS) compared to baseline. Calculation: Sum of Pain intensity difference (SPID) is the time-weighted summary measure of the total area under the pain intensity difference (PID) curve that integrates serial assessments of pain during x times after the first Investigational Medicinal Product SPID0-6h= SPID0-30min+SPID30min-45min+SPID45min-1h+SPID1h-1h30+SPID1h30-2h+SPID2h-2h30+SPID2h30-3h+SPID3h-4h+SPID4h-5h+SPID5h-6h With: SPIDTime1-Time2 = (PID Theoretical Time1 + PID Theoretical Time2) \* (Theoretical Time2- Theoretical Time1) / 2 SPID min 0-6h = 0 SPID max 0-6h = 36000 The lower score mean a better score
Total Pain Relief at 6 Hours (TOTPAR0-6h)
时间窗: 6 hours post-dose
Pain Relief will be assessed by the patient at defined time points (T30, T45, T60, T90, T120, T150, T180, T240, T300, T360 min) after the first IMP intake and/or right before first intake of rescue medication using a 5-point verbal rating scale (VRS). Calculation: TOTPAR is the time-weighted summary measure of the total area under the pain release difference curve that integrates serial assessments of pain release during x times after the first Investigational Medicinal Product TOTPAR0-6h=TOTPAR0-30min+TOTPAR30min-45min+TOTPAR45min-1h+TOTPAR1h-1h30+TOTPAR1h30-2h+TOTPAR2h-2h30+TOTPAR2h30-3h+ TOTPAR 3h-4h+ TOTPAR 4h-5h+ TOTPAR 5h-6h With: TOTPARTime1-Time2 = (PAR Time1 + PAR Time2) \* (Time2-Time1) / 2 And with the score of pain relief at T0 = 0 ("none") TOTPAR min 0-6h = 0 TOTPAR max 0-6h = 1800 The higher score mean a better outcome
Proportion of Responder Patients
时间窗: 6 hours post-dose
A responder patient is a subject who achieves a reduction of 50% of pain intensity compared to baseline.
The Patient's Global Impression of Change (PGIC) Questionnaire
时间窗: 6 hours post-dose
The Onset of Pain Relief
时间窗: during the first 6 hours
Score of pain intensity will be assessed by the patient at defined time points (T30, T45, T60, T90, T120, T150, T180, T240, T300, T360 min). The time point of the first assessment obtaining a score ≤ 30 mm will be retained as time score of onset of pain relief.
次要结局
- Total Pain Relief at 1 Hour (TOTPAR0-1h), 2 Hours (TOTPAR0-2h), 3 Hours (TOTPAR0-3h), and 4 Hours (TOTPAR0-4h)(At 1 hour, 2 hours, 3 hours, and 4 hours)
- Sum of Pain Intensity Differences at 1 Hour (SPID0-1h), 2 Hours (SPID0-2h), 3 Hours (SPID0-3h), and 4 Hours (SPID0-4h)(At 1 hour, 2 hours, 3 hours, and 4 hours)
- The Pain Intensity Differences (PID) Assessment(At each timepoint: 30min, At 45min, until at 360 min post-dose)
- Proportion of Responder Patients.(At 1 hour, 2 hours, 3 hours and 4 hours.)
- Time to the Second Investigational Medicinal Product (IMP) Intake(Up to 5 days after first dose)
- Participant Having Taken a Rescue Analgesic Treatment(Up to 10 days after first dose)
- Sum of Pain Intensity Differences(At days 1, 2, 3, 4 and 5)
- Proportion of Patients Having Taken a Rescue Analgesic Treatment Throughout the Study.(Up to 10 days after first dose)
- The Total Dose of Rescue Medication Taken.(Up to 10 days after first dose)
- Mean Duration Under Rescue Medication Over the 5 Days.(Up to 5 days after first dose)
- Number of Investigational Medicinal Product (IMP) Intakes(Up to 5 days after first dose)
- Patient's Global Impression of Change (PGIC) Score(Up to 10 days after first dose)