Bioequivalence of IMP 08P1902F0 Relative to Contramal® (100 mg/mL Oral Solution)

Study Overview
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Brief Summary
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This study aims to demonstrate the bioequivalence between the formulation of 5 mg/mL Tramadol Hydrochloride Oral Solution (08P1902F0) Relative to the reference product Contramal® (100 mg/mL Oral Solution).

Official Title
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Comparative Randomized, Single Dose, Two-Way Crossover Open Label Study To Determine The Bioequivalence Of 5 mg/mL Tramadol Hydrochloride Oral Solution (08P1902F0) Relative To Contramal® (100 mg/mL Oral Solution) After An Oral Administration

Conditions
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Healthy

Intervention / Treatment
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* Drug: Tramadol Hydrochloride 5 MG/ML Oral Solution
* Drug: Tramadol Hydrochloride 100 MG/ML Oral Solution (Contramal(r))


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and non-pregnant female human subjects, age 18-50 years Body mass index between 18.5-30 Kg/m² Subject with normal findings Willingness to follow the protocol requirements Exclusion Criteria: History of hypersensitivity to tramadol hydrochloride Significant history of asthma, thyrotoxicosis, tumours, peptic or gastric ulcer, gastrointestinal malabsorption or haemorrhage in the gastro-intestinal tract, sinusitis, pharyngitis, renal disorder (impaired renal function), hepatic disorder (impaired hepatic function), cardiovascular disorder (ex. severe heart failure), neurological disease such as epilepsy, haematological disorders or diabetes, psychiatric, dermatologic or immunological disorders Presence of any clinically significant results from laboratory tests, lactating female or woman of childbearing potential unwilling to use an effective contraception

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Open-label, randomized, single dose, two-sequence, two-period crossover study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tramadol hydrochloride 5mg/mL oral solution (IMP 08P1902F0)<br> | Drug: Tramadol Hydrochloride 5 MG/ML Oral Solution<br>* 50mg (10mL) single dose<br>|
| Active Comparator: Tramadol hydrochloride 100mg/mL oral solution (Contramal(r))<br> | Drug: Tramadol Hydrochloride 100 MG/ML Oral Solution (Contramal(r))<br>* 50mg (20 drops) single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of tramadol hydrochloride for the test and the reference products | The maximum concentration in plasma among observed concentrations at pre-specified time points | predose, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours | 
| AUC0-t of tramadol hydrochloride for the test and the reference products | The area under the plasma concentration versus time curve from time 0 to the last measured concentration | predose, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-infinity of tramadol hydrochloride for the test and the reference products | The area under the plasma concentration versus time curve from time 0 to to infinite time | predose, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours | 
| Kel of tramadol hydrochloride for the test and the reference products | The elimination rate constant | predose, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours | 
| Tmax of tramadol hydrochloride for the test and the reference products | Plasma Elimination Half-Life | predose, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours | 
| T1/2 of tramadol hydrochloride for the test and the reference products | Plasma Elimination Half-Life | predose, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours | 
| Incidence of treatment-related adverse events | Occurence and severity of adverse events (serious and non serious adverse events) | Day 1 to Day 11 (end of study) |