Healthy Volunteers
Conditions
Brief summary
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.
Interventions
DRUGnefopam hydrochloride 30mg X2
nefopam hydrochloride 30mg X2
DRUGparacetamol 500 mg X2
paracetamol 500 mg X2
DRUGCombination Product: nefopam hydrochloride 30mg / paracetamol 500mg X2
Combination Product: nefopam hydrochloride 30mg / paracetamol 500mg X2
Sponsors
Accutest Research Laboratories (I) Pvt. Ltd.
Unither Pharmaceuticals, France
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Intervention model description
An open-label, randomized, four-period, four treatments, cross-over trial in healthy volunteers
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | up to 48 hours post 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Paracetamol Metabolites Pharmacokinetic Profiles in Each Arms After Single Dose | up to 48 hours post 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 |
| N-desmethyl-nefopam Pharmacokinetic Profiles in Each Arms After Single Dose | up to 48 hours post 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 |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Up to 48 hours | Occurrence and severity of adverse events (serious and non-serious adverse events) |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All study participants has receivent every interventions | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Forth Period | Protocol Violation | 0 | 1 | 0 | 0 |
| Forth Period | Withdrawal by Subject | 0 | 0 | 1 | 0 |
| Second Period | Adverse Event | 1 | 0 | 0 | 0 |
| Second Period | Protocol Violation | 0 | 0 | 0 | 1 |
| Third Period | Protocol Violation | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | All Study Participants | — |
|---|---|---|
| Age, Continuous | 32.97 years STANDARD_DEVIATION 6.18 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment India | 32 participants | — |
| Sex: Female, Male Female | 12 Participants | — |
| Sex: Female, Male Male | 20 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 1 / 32 | 1 / 32 | 0 / 32 | 1 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 32 |
Outcome results
Primary
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
Time frame: up to 48 hours post dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FDC Nefopam Hydrochloride 30mg / Paracetamol 500mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Nefopam | 1206.310 ng*hr/mM | Standard Deviation 541.682 |
| FDC Nefopam Hydrochloride 30mg / Paracetamol 500mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Paracetamol | 71402.500 ng*hr/mM | Standard Deviation 21114.375 |
| Nefopam Hydrochloride 30mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Paracetamol | NA ng*hr/mM | — |
| Nefopam Hydrochloride 30mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Nefopam | 1275.371 ng*hr/mM | Standard Deviation 511.415 |
| Paracetamol 500mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Nefopam | NA ng*hr/mM | — |
| Paracetamol 500mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Paracetamol | 81877.185 ng*hr/mM | Standard Deviation 24007.993 |
| Nefopam Hydrochloride 30mg and Paracetamol 500mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Nefopam | 1268.071 ng*hr/mM | Standard Deviation 527.581 |
| Nefopam Hydrochloride 30mg and Paracetamol 500mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Paracetamol | 78454.622 ng*hr/mM | Standard Deviation 23857.199 |
Primary
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
Time frame: up to 48 hours post dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FDC Nefopam Hydrochloride 30mg / Paracetamol 500mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Nefopam | 101.808 ng/mL | Standard Deviation 38.283 |
| FDC Nefopam Hydrochloride 30mg / Paracetamol 500mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Paracetamol | 13136.299 ng/mL | Standard Deviation 4292.658 |
| Nefopam Hydrochloride 30mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Paracetamol | NA ng/mL | — |
| Nefopam Hydrochloride 30mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Nefopam | 114.957 ng/mL | Standard Deviation 40.071 |
| Paracetamol 500mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Nefopam | NA ng/mL | — |
| Paracetamol 500mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Paracetamol | 21051.399 ng/mL | Standard Deviation 8155.946 |
| Nefopam Hydrochloride 30mg and Paracetamol 500mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Nefopam | 118.528 ng/mL | Standard Deviation 47.616 |
| Nefopam Hydrochloride 30mg and Paracetamol 500mg | Nefopam and Paracetamol Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Paracetamol | 17596.380 ng/mL | Standard Deviation 6431.919 |
Secondary
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Occurrence and severity of adverse events (serious and non-serious adverse events)
Time frame: Up to 48 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FDC Nefopam Hydrochloride 30mg / Paracetamol 500mg | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 1 event |
| Nefopam Hydrochloride 30mg | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 1 event |
| Paracetamol 500mg | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 0 event |
| Nefopam Hydrochloride 30mg and Paracetamol 500mg | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 2 event |
Secondary
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
Time frame: up to 48 hours post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC Nefopam Hydrochloride 30mg / Paracetamol 500mg | N-desmethyl-nefopam Pharmacokinetic Profiles in Each Arms After Single Dose | 671.457 ng*hr/mL | Standard Deviation 228.793 |
| Nefopam Hydrochloride 30mg | N-desmethyl-nefopam Pharmacokinetic Profiles in Each Arms After Single Dose | 679.468 ng*hr/mL | Standard Deviation 239.053 |
| Paracetamol 500mg | N-desmethyl-nefopam Pharmacokinetic Profiles in Each Arms After Single Dose | 692.628 ng*hr/mL | Standard Deviation 239.316 |
Secondary
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
Time frame: up to 48 hours post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC Nefopam Hydrochloride 30mg / Paracetamol 500mg | N-desmethyl-nefopam Pharmacokinetic Profiles in Each Arms After Single Dose | 31.740 ng/mL | Standard Deviation 13.996 |
| Nefopam Hydrochloride 30mg | N-desmethyl-nefopam Pharmacokinetic Profiles in Each Arms After Single Dose | 31.402 ng/mL | Standard Deviation 13.71 |
| Paracetamol 500mg | N-desmethyl-nefopam Pharmacokinetic Profiles in Each Arms After Single Dose | 32.279 ng/mL | Standard Deviation 14.097 |
Secondary
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
Time frame: up to 48 hours post dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FDC Nefopam Hydrochloride 30mg / Paracetamol 500mg | Paracetamol Metabolites Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Paracetamol Sulfate | 53400.117 ng*hr/mL | Standard Deviation 15051.893 |
| FDC Nefopam Hydrochloride 30mg / Paracetamol 500mg | Paracetamol Metabolites Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Paracetamol Glucuronide | 848700.451 ng*hr/mL | Standard Deviation 200394.87 |
| Nefopam Hydrochloride 30mg | Paracetamol Metabolites Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Paracetamol Sulfate | 56726.962 ng*hr/mL | Standard Deviation 16795.844 |
| Nefopam Hydrochloride 30mg | Paracetamol Metabolites Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Paracetamol Glucuronide | 895791.865 ng*hr/mL | Standard Deviation 237880.738 |
| Paracetamol 500mg | Paracetamol Metabolites Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Paracetamol Sulfate | 54559.464 ng*hr/mL | Standard Deviation 16443.774 |
| Paracetamol 500mg | Paracetamol Metabolites Pharmacokinetic Profiles in Each Arms After Single Dose | AUC Paracetamol Glucuronide | 857425.472 ng*hr/mL | Standard Deviation 209544.721 |
Secondary
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
Time frame: up to 48 hours post dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FDC Nefopam Hydrochloride 30mg / Paracetamol 500mg | Paracetamol Metabolites Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Paracetamol Sulfate | 6696.526 ng/mL | Standard Deviation 1498.384 |
| FDC Nefopam Hydrochloride 30mg / Paracetamol 500mg | Paracetamol Metabolites Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Paracetamol Glucuronide | 104919.677 ng/mL | Standard Deviation 34090.92 |
| Nefopam Hydrochloride 30mg | Paracetamol Metabolites Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Paracetamol Sulfate | 7110.342 ng/mL | Standard Deviation 1664.241 |
| Nefopam Hydrochloride 30mg | Paracetamol Metabolites Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Paracetamol Glucuronide | 111556.414 ng/mL | Standard Deviation 38095.339 |
| Paracetamol 500mg | Paracetamol Metabolites Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Paracetamol Sulfate | 7064.836 ng/mL | Standard Deviation 1746.416 |
| Paracetamol 500mg | Paracetamol Metabolites Pharmacokinetic Profiles in Each Arms After Single Dose | Cmax Paracetamol Glucuronide | 108171.336 ng/mL | Standard Deviation 37716.515 |