Pharmacokinetic Study of a Fixed Dose Combination Nefopam Hydrochloride (30 mg) / Paracetamol (500 mg)

Study Overview
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Brief Summary
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This study aims to assess the pharmacokinetic profile of a Fixed Dose Combination nefopam hydrochloride (30 mg) / paracetamol (500 mg) and individual components taken alone or concomitantly after oral single dose.

Official Title
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Pharmacokinetic Study of a Fixed Dose Combination Nefopam Hydrochloride (30 mg) / Paracetamol (500 mg) and Individual Nefopam Hydrochloride and Paracetamol Taken Alone or Concomitantly After Oral Single Dose

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: nefopam hydrochloride 30mg X2
* Drug: paracetamol 500 mg X2
* Drug: Combination Product: nefopam hydrochloride 30mg / paracetamol 500mg X2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and non-pregnant female human subjects, age 18 - 45 years. Body Mass Index between 18.5-30 Kg / m2 . Subjects with normal findings . Willingness to follow the protocol requirements Exclusion Criteria: Known history of hypersensitivity to Nefopam, Paracetamol or related drugs. Requiring medication for any ailment having enzyme-modifying activity in the previous 28 days, prior to dosing day. Subjects with a history of convulsive disorders. Subject with a moderate or severe renal impairment History of cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic, haematological, gastrointestinal, endocrine, immunological or psychiatric diseases. Female subjects not confirming to using birth control measures,

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: An open-label, randomized, four-period, four treatments, cross-over trial in healthy volunteers
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FDC nefopam hydrochloride 30mg / paracetamol 500mg<br>Single dose: 2 tablets | Drug: Combination Product: nefopam hydrochloride 30mg / paracetamol 500mg X2<br>* Combination Product: nefopam hydrochloride 30mg / paracetamol 500mg X2<br>|
| Active Comparator: nefopam hydrochloride 30mg<br>Single dose: 2 tablets | Drug: nefopam hydrochloride 30mg X2<br>* nefopam hydrochloride 30mg X2<br>|
| Active Comparator: paracetamol 500mg<br>Single dose: 2 tablets | Drug: paracetamol 500 mg X2<br>* paracetamol 500 mg X2<br>* Other names: acetaminophen;|
| Active Comparator: nefopam hydrochloride 30mg and paracetamol 500mg<br>Single dose: 2 tablets | Drug: nefopam hydrochloride 30mg X2<br>* nefopam hydrochloride 30mg X2<br>Drug: paracetamol 500 mg X2<br>* paracetamol 500 mg X2<br>* Other names: acetaminophen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nefopam and Paracetamol Pharmacokinetic profiles in each arms after single dose | Peak Plasma Concentration (Cmax) of nefopam hydrochloride and paracetamol after single dose at different timepoints : Within 60 min before drug administration),0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours | up to 48 hours post dose | 
| Nefopam and Paracetamol Pharmacokinetic profiles in each arms after single dose | Area under the plasma concentration versus time curve (AUC) of nefopam hydrochloride and paracetamol after single dose at different timepoints : Within 60 min before drug administration),0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours | up to 48 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Paracetamol metabolites Pharmacokinetic profiles in each arms after single dose | Peak Plasma Concentration (Cmax) of main paracetamol metabolites (Sulfate and Glucuronide) after single dose at different timepoints : Within 60 min before drug administration),0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours | up to 48 hours post dose | 
| Paracetamol metabolites Pharmacokinetic profiles in each arms after single dose | Area under the plasma concentration versus time curve (AUC) of main paracetamol metabolites (Sulfate and Glucuronide) after single dose at different timepoints : Within 60 min before drug administration),0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours | up to 48 hours post dose | 
| N-desmethyl-nefopam Pharmacokinetic profiles in each arms after single dose | Peak Plasma Concentration (Cmax) of N-desmethyl-nefopam after single dose at different timepoints : Within 60 min before drug administration),0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours | up to 48 hours post dose | 
| N-desmethyl-nefopam Pharmacokinetic profiles in each arms after single dose | Area under the plasma concentration versus time curve (AUC) of N-desmethyl-nefopam after single dose at different timepoints : Within 60 min before drug administration),0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours | up to 48 hours post dose | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Occurrence and severity of adverse events (serious and non-serious adverse events) | Up to 48 hours |